The Role of Interferon Regulatory Factors in Liver Diseases
Abstract
:1. Introduction
Materials and Methods
2. The Structure and Function of IRFs
3. IRFs and Liver Diseases
3.1. IRFs and Liver Ischemia-Reperfusion Injury
3.1.1. Autophagy and Oxidative Stress
3.1.2. Inflammatory Cytokines
3.2. IRFs and Alcohol-Induced Liver Injury/Alcoholic Liver Disease
3.3. IRFs and Con A-Induced Liver Injury
3.4. IRFs and Post-Transplantation/Other Modes of Liver Injury
3.5. IRFs and Nonalcoholic Fatty Liver Disease
3.6. IRFs and Liver Fibrosis
3.7. IRFs and Hepatocellular Carcinoma
4. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Jefferies, C.A. Regulating IRFs in IFN Driven Disease. Front. Immunol. 2019, 10, 441432. [Google Scholar] [CrossRef] [PubMed]
- Zhou, H.; Tang, Y.D.; Zheng, C. Revisiting IRF1-mediated antiviral innate immunity. Cytokine Growth Factor Rev. 2022, 64, 1–6. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Zhang, X.; Wang, G.; Wang, L.; Lin, Y.; Sun, F. Hsa-miR-513b-5p suppresses cell proliferation and promotes P53 expression by targeting IRF2 in testicular embryonal carcinoma cells. Gene 2017, 626, 344–353. [Google Scholar] [CrossRef] [PubMed]
- Liao, W.; Overman, M.J.; Boutin, A.T.; Shang, X.; Zhao, D.; Dey, P.; Li, J.; Wang, G.; Lan, Z.; Li, J.; et al. KRAS-IRF2 Axis Drives Immune Suppression and Immune Therapy Resistance in Colorectal Cancer. Cancer Cell 2019, 35, 559–572.e7. [Google Scholar] [CrossRef] [PubMed]
- Guo, Y.; Xu, J.; Du, Q.; Yan, Y.; Geller, D.A. IRF2 regulates cellular survival and Lenvatinib-sensitivity of hepatocellular carcinoma (HCC) through regulating β-catenin. Transl. Oncol. 2021, 14, 101059. [Google Scholar] [CrossRef] [PubMed]
- Qing, F.; Liu, Z. Interferon regulatory factor 7 in inflammation, cancer and infection. Front. Immunol. 2023, 14, 1190841. [Google Scholar] [CrossRef]
- Ma, W.; Huang, G.; Wang, Z.; Wang, L.; Gao, Q. IRF7: Role and regulation in immunity and autoimmunity. Front. Immunol. 2023, 14, 1236923. [Google Scholar] [CrossRef] [PubMed]
- Al Hamrashdi, M.; Brady, G. Regulation of IRF3 activation in human antiviral signaling pathways. Biochem. Pharmacol. 2022, 200, 115026. [Google Scholar] [CrossRef]
- Kaur, A.; Lee, L.H.; Chow, S.C.; Fang, C.M. IRF5-mediated immune responses and its implications in immunological disorders. Int. Rev. Immunol. 2018, 37, 229–248. [Google Scholar] [CrossRef]
- Wong, R.W.J.; Ong, J.Z.L.; Theardy, M.S.; Sanda, T. IRF4 as an Oncogenic Master Transcription Factor. Cancers 2022, 14, 4314. [Google Scholar] [CrossRef]
- Moorman, H.R.; Reategui, Y.; Poschel, D.B.; Liu, K. IRF8: Mechanism of Action and Health Implications. Cells 2022, 11, 2630. [Google Scholar] [CrossRef] [PubMed]
- Schutte, B.C.; Saal, H.M.; Goudy, S.; Leslie, E.J. IRF6-Related Disorders. In GeneReviews(®); Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., Amemiya, A., Eds.; University of Washington: Seattle, WA, USA, 1993. [Google Scholar]
- Fink, K.; Grandvaux, N. STAT2 and IRF9: Beyond ISGF3. Jakstat 2013, 2, e27521. [Google Scholar] [CrossRef] [PubMed]
- Paul, A.; Ismail, M.N.; Tang, T.H.; Ng, S.K. Phosphorylation of interferon regulatory factor 9 (IRF9). Mol. Biol. Rep. 2023, 50, 3909–3917. [Google Scholar] [CrossRef] [PubMed]
- Li, L.; Chen, S.N.; Nie, P. IRF11 regulates positively type I IFN transcription and antiviral response in mandarin fish, Siniperca chuatsi. Dev. Comp. Immunol. 2021, 114, 103846. [Google Scholar] [CrossRef] [PubMed]
- Tsung, A.; Stang, M.T.; Ikeda, A.; Critchlow, N.D.; Izuishi, K.; Nakao, A.; Chan, M.H.; Jeyabalan, G.; Yim, J.H.; Geller, D.A. The transcription factor interferon regulatory factor-1 mediates liver damage during ischemia-reperfusion injury. Am. J. Physiol.-Gastrointest. Liver Physiol. 2006, 290, G1261–G1268. [Google Scholar] [CrossRef] [PubMed]
- Ueki, S.; Dhupar, R.; Cardinal, J.; Tsung, A.; Yoshida, J.; Ozaki, K.S.; Klune, J.R.; Murase, N.; Geller, D.A. Critical role of interferon regulatory factor-1 in murine liver transplant ischemia reperfusion injury. Hepatology 2010, 51, 1692–1701. [Google Scholar] [CrossRef] [PubMed]
- Nakano, R.; Chogahara, I.; Ohira, M.; Imaoka, K.; Sato, S.; Bekki, T.; Sato, K.; Imaoka, Y.; Marlen, D.; Tanaka, Y.; et al. Atherosclerosis Deteriorates Liver Ischemia/Reperfusion Injury Via Interferon Regulatory Factor-1 Overexpression in a Murine Model. Transplant. Proc. 2024, 56, 678–685. [Google Scholar] [CrossRef] [PubMed]
- Castellaneta, A.; Yoshida, O.; Kimura, S.; Yokota, S.; Geller, D.A.; Murase, N.; Thomson, A.W. Plasmacytoid dendritic cell-derived IFN-α promotes murine liver ischemia/reperfusion injury by induction of hepatocyte IRF-1. Hepatology 2014, 60, 267–277. [Google Scholar] [CrossRef] [PubMed]
- Kim, K.-H.; Dhupar, R.; Ueki, S.; Cardinal, J.; Pan, P.; Cao, Z.; Cho, S.W.; Murase, N.; Tsung, A.; Geller, D.A. Donor graft interferon regulatory factor-1 gene transfer worsens liver transplant ischemia/reperfusion injury. Surgery 2009, 146, 181–189. [Google Scholar] [CrossRef]
- Klune, J.R.; Bartels, C.; Luo, J.; Yokota, S.; Du, Q.; Geller, D.A. IL-23 mediates murine liver transplantation ischemia-reperfusion injury via IFN-γ/IRF-1 pathway. Am. J. Physiol.-Gastrointest. Liver Physiol. 2018, 315, G991–G1002. [Google Scholar] [CrossRef]
- Honda, K.; Taniguchi, T. IRFs: Master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat. Rev. Immunol. 2006, 6, 644–658. [Google Scholar] [CrossRef] [PubMed]
- Ghazarian, M.; Revelo, X.S.; Nøhr, M.K.; Luck, H.; Zeng, K.; Lei, H.; Tsai, S.; Schroer, S.A.; Park, Y.J.; Chng, M.H.Y.; et al. Type I Interferon Responses Drive Intrahepatic T cells to Promote Metabolic Syndrome. Sci. Immunol. 2017, 2, eaai7616. [Google Scholar] [CrossRef] [PubMed]
- Vadrot, N.; Legrand, A.; Nello, E.; Bringuier, A.F.; Guillot, R.; Feldmann, G. Inducible nitric oxide synthase (iNOS) activity could be responsible for resistance or sensitivity to IFN-gamma-induced apoptosis in several human hepatoma cell lines. J. Interferon Cytokine Res. 2006, 26, 901–913. [Google Scholar] [CrossRef] [PubMed]
- Detjen, K.M.; Murphy, D.; Welzel, M.; Farwig, K.; Wiedenmann, B.; Rosewicz, S. Downregulation of p21(waf/cip-1) mediates apoptosis of human hepatocellular carcinoma cells in response to interferon-gamma. Exp. Cell Res. 2003, 282, 78–89. [Google Scholar] [CrossRef] [PubMed]
- Gao, J.; Senthil, M.; Ren, B.; Yan, J.; Xing, Q.; Yu, J.; Zhang, L.; Yim, J.H. IRF-1 transcriptionally upregulates PUMA, which mediates the mitochondrial apoptotic pathway in IRF-1-induced apoptosis in cancer cells. Cell Death Differ. 2010, 17, 699–709. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.N.; Liu, J.X.; Hu, Y.W.; Chen, H.; Yuan, Z.H. Hyper-activated IRF-1 and STAT1 contribute to enhanced interferon stimulated gene (ISG) expression by interferon alpha and gamma co-treatment in human hepatoma cells. Biochim. Biophys. Acta 2006, 1759, 417–425. [Google Scholar] [CrossRef] [PubMed]
- Tada, S.; Saito, H.; Tsunematsu, S.; Ebinuma, H.; Wakabayashi, K.; Masuda, T.; Ishii, H. Interferon regulatory factor-1 gene abnormality and loss of growth inhibitory effect of interferon-alpha in human hepatoma cell lines. Int. J. Oncol. 1998, 13, 1207–1216. [Google Scholar] [CrossRef]
- Yan, Y.; Zheng, L.; Du, Q.; Yazdani, H.; Dong, K.; Guo, Y.; Geller, D.A. Interferon regulatory factor 1(IRF-1) activates anti-tumor immunity via CXCL10/CXCR3 axis in hepatocellular carcinoma (HCC). Cancer Lett. 2021, 506, 95–106. [Google Scholar] [CrossRef]
- Wang, R.; Guo, H.; Tang, X.; Zhang, T.; Liu, Y.; Zhang, C.; Yu, H.; Li, Y. Interferon Gamma-Induced Interferon Regulatory Factor 1 Activates Transcription of HHLA2 and Induces Immune Escape of Hepatocellular Carcinoma Cells. Inflammation 2022, 45, 308–330. [Google Scholar] [CrossRef]
- Taniguchi, T.; Ogasawara, K.; Takaoka, A.; Tanaka, N. IRF family of transcription factors as regulators of host defense. Annu. Rev. Immunol. 2001, 19, 623–655. [Google Scholar] [CrossRef]
- Barnes, B.; Lubyova, B.; Pitha, P.M. On the role of IRF in host defense. J. Interferon Cytokine Res. 2002, 22, 59–71. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, H.; Hiscott, J.; Pitha, P.M. The growing family of interferon regulatory factors. Cytokine Growth Factor. Rev. 1997, 8, 293–312. [Google Scholar] [CrossRef] [PubMed]
- Chen, W.; Lam, S.S.; Srinath, H.; Jiang, Z.; Correia, J.J.; Schiffer, C.A.; Fitzgerald, K.A.; Lin, K.; Royer, W.E., Jr. Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5. Nat. Struct. Mol. Biol. 2008, 15, 1213–1220. [Google Scholar] [CrossRef] [PubMed]
- Ikushima, H.; Negishi, H.; Taniguchi, T. The IRF Family Transcription Factors at the Interface of Innate and Adaptive Immune Responses. Cold Spring Harb. Symp. Quant. Biol. 2013, 78, 105–116. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.-J.; Li, J.; Lu, N.; Shen, X.-Z. Interferon regulatory factors: A key to tumour immunity. Int. Immunopharmacol. 2017, 49, 1–5. [Google Scholar] [CrossRef] [PubMed]
- Storchi, L.; Remoli, A.L.; Marsili, G.; Acchioni, C.; Acchioni, M.; Battistini, A.; Sgarbanti, M.; Marrone, A. A model of the three-dimensional structure of human interferon responsive factor 1 and its modifications upon phosphorylation or phosphorylation-mimicking mutations. J. Biomol. Struct. Dyn. 2019, 37, 4632–4643. [Google Scholar] [CrossRef] [PubMed]
- Forero, A.; Ozarkar, S.; Li, H.; Lee, C.H.; Hemann, E.A.; Nadjsombati, M.S.; Hendricks, M.R.; So, L.; Green, R.; Roy, C.N.; et al. Differential Activation of the Transcription Factor IRF1 Underlies the Distinct Immune Responses Elicited by Type I and Type III Interferons. Immunity 2019, 51, 451–464.e6. [Google Scholar] [CrossRef] [PubMed]
- Schoggins, J.W.; Wilson, S.J.; Panis, M.; Murphy, M.Y.; Jones, C.T.; Bieniasz, P.; Rice, C.M. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 2011, 472, 481–485. [Google Scholar] [CrossRef] [PubMed]
- Venkatesh, D.; Ernandez, T.; Rosetti, F.; Batal, I.; Cullere, X.; Luscinskas, F.W.; Zhang, Y.; Stavrakis, G.; García-Cardeña, G.; Horwitz, B.H.; et al. Endothelial TNF Receptor 2 Induces IRF1 Transcription Factor-Dependent Interferon-β Autocrine Signaling to Promote Monocyte Recruitment. Immunity 2013, 38, 1025–1037. [Google Scholar] [CrossRef]
- Yamane, D.; Feng, H.; Rivera-Serrano, E.E.; Selitsky, S.R.; Hirai-Yuki, A.; Das, A.; McKnight, K.L.; Misumi, I.; Hensley, L.; Lovell, W.; et al. Basal expression of interferon regulatory factor 1 drives intrinsic hepatocyte resistance to multiple RNA viruses. Nat. Microbiol. 2019, 4, 1096–1104. [Google Scholar] [CrossRef]
- Feng, H.; Lenarcic, E.M.; Yamane, D.; Wauthier, E.; Mo, J.; Guo, H.; McGivern, D.R.; González-López, O.; Misumi, I.; Reid, L.M.; et al. NLRX1 promotes immediate IRF1-directed antiviral responses by limiting dsRNA-activated translational inhibition mediated by PKR. Nat. Immunol. 2017, 18, 1299–1309. [Google Scholar] [CrossRef]
- Blumenthal, A.; Feng, H.; Zhang, Y.-B.; Gui, J.-F.; Lemon, S.M.; Yamane, D. Interferon regulatory factor 1 (IRF1) and anti-pathogen innate immune responses. PLoS Pathog. 2021, 17, e1009220. [Google Scholar] [CrossRef]
- Rueschenbaum, S.; Cai, C.; Schmidt, M.; Schwarzkopf, K.; Dittmer, U.; Zeuzem, S.; Welsch, C.; Lange, C.M. Translation of IRF-1 Restricts Hepatic Interleukin-7 Production to Types I and II Interferons: Implications for Hepatic Immunity. Front. Immunol. 2021, 11, 581352. [Google Scholar] [CrossRef] [PubMed]
- Klune, J.R.; Dhupar, R.; Kimura, S.; Ueki, S.; Cardinal, J.; Nakao, A.; Nace, G.; Evankovich, J.; Murase, N.; Tsung, A.; et al. Interferon regulatory factor-2 is protective against hepatic ischemia-reperfusion injury. Am. J. Physiol.-Gastrointest. Liver Physiol. 2012, 303, G666–G673. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Li, H.; Xue, B.; Deng, R.; Huang, X.; Xu, Y.; Chen, S.; Tian, R.; Wang, X.; Xun, Z.; et al. IRF1 Promotes the Innate Immune Response to Viral Infection by Enhancing the Activation of IRF3. J. Virol. 2020, 94, 10-1128. [Google Scholar] [CrossRef]
- Glanz, A.; Chakravarty, S.; Fan, S.; Chawla, K.; Subramanian, G.; Rahman, T.; Walters, D.; Chakravarti, R.; Chattopadhyay, S. Autophagic degradation of IRF3 induced by the small-molecule auranofin inhibits its transcriptional and proapoptotic activities. J. Biol. Chem. 2021, 297, 101274. [Google Scholar] [CrossRef]
- Yuan, J.; Liu, Z.; Wu, Z.; Yang, J.; Yang, J. Construction and validation of an IRF4 risk score to predict prognosis and response to immunotherapy in hepatocellular carcinoma. Int. Immunopharmacol. 2022, 113, 109411. [Google Scholar] [CrossRef] [PubMed]
- Eguchi, J.; Kong, X.; Tenta, M.; Wang, X.; Kang, S.; Rosen, E.D. Interferon Regulatory Factor 4 Regulates Obesity-Induced Inflammation Through Regulation of Adipose Tissue Macrophage Polarization. Diabetes 2013, 62, 3394–3403. [Google Scholar] [CrossRef]
- Takaoka, A.; Yanai, H.; Kondo, S.; Duncan, G.; Negishi, H.; Mizutani, T.; Kano, S.; Honda, K.; Ohba, Y.; Mak, T.W.; et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 2005, 434, 243–249. [Google Scholar] [CrossRef]
- Krausgruber, T.; Blazek, K.; Smallie, T.; Alzabin, S.; Lockstone, H.; Sahgal, N.; Hussell, T.; Feldmann, M.; Udalova, I.A. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat. Immunol. 2011, 12, 231–238. [Google Scholar] [CrossRef]
- Saliba, D.G.; Heger, A.; Eames, H.L.; Oikonomopoulos, S.; Teixeira, A.; Blazek, K.; Androulidaki, A.; Wong, D.; Goh, F.G.; Weiss, M.; et al. IRF5:RelA interaction targets inflammatory genes in macrophages. Cell Rep. 2014, 8, 1308–1317. [Google Scholar] [CrossRef]
- Weiss, M.; Blazek, K.; Byrne, A.J.; Perocheau, D.P.; Udalova, I.A. IRF5 is a specific marker of inflammatory macrophages in vivo. Mediat. Inflamm. 2013, 2013, 245804. [Google Scholar] [CrossRef]
- Almuttaqi, H.; Udalova, I.A. Advances and challenges in targeting IRF5, a key regulator of inflammation. FEBS J. 2018, 286, 1624–1637. [Google Scholar] [CrossRef]
- Khoyratty, T.E.; Udalova, I.A. Diverse mechanisms of IRF5 action in inflammatory responses. Int. J. Biochem. Cell Biol. 2018, 99, 38–42. [Google Scholar] [CrossRef] [PubMed]
- Alzaid, F.; Lagadec, F.; Albuquerque, M.; Ballaire, R.; Orliaguet, L.; Hainault, I.; Blugeon, C.; Lemoine, S.; Lehuen, A.; Saliba, D.G.; et al. IRF5 governs liver macrophage activation that promotes hepatic fibrosis in mice and humans. JCI Insight 2016, 1, e88689. [Google Scholar] [CrossRef] [PubMed]
- Kim, I.K.; Diamond, M.S.; Yuan, S.; Kemp, S.B.; Kahn, B.M.; Li, Q.; Lin, J.H.; Li, J.; Norgard, R.J.; Thomas, S.K.; et al. Plasticity-induced repression of Irf6 underlies acquired resistance to cancer immunotherapy in pancreatic ductal adenocarcinoma. Nat. Commun. 2024, 15, 1532. [Google Scholar] [CrossRef] [PubMed]
- Li, D.; Cheng, P.; Wang, J.; Qiu, X.; Zhang, X.; Xu, L.; Liu, Y.; Qin, S. IRF6 Is Directly Regulated by ZEB1 and ELF3, and Predicts a Favorable Prognosis in Gastric Cancer. Front. Oncol. 2019, 9, 220. [Google Scholar] [CrossRef]
- Tong, J.; Han, C.J.; Zhang, J.Z.; He, W.Z.; Zhao, G.J.; Cheng, X.; Zhang, L.; Deng, K.Q.; Liu, Y.; Fan, H.F.; et al. Hepatic Interferon Regulatory Factor 6 Alleviates Liver Steatosis and Metabolic Disorder by Transcriptionally Suppressing Peroxisome Proliferator-Activated Receptor γ in Mice. Hepatology 2019, 69, 2471–2488. [Google Scholar] [CrossRef] [PubMed]
- Tan, L.; Qu, W.; Wu, D.; Liu, M.; Ai, Q.; Hu, H.; Wang, Q.; Chen, W.; Zhou, H. The interferon regulatory factor 6 promotes cisplatin sensitivity in colorectal cancer. Bioengineered 2022, 13, 10504–10517. [Google Scholar] [CrossRef]
- Ning, S.; Pagano, J.S.; Barber, G.N. IRF7: Activation, regulation, modification and function. Genes. Immun. 2011, 12, 399–414. [Google Scholar] [CrossRef]
- Luo, W.W.; Tong, Z.; Cao, P.; Wang, F.B.; Liu, Y.; Zheng, Z.Q.; Wang, S.Y.; Li, S.; Wang, Y.Y. Transcription-independent regulation of STING activation and innate immune responses by IRF8 in monocytes. Nat. Commun. 2022, 13, 4822. [Google Scholar] [CrossRef] [PubMed]
- Salem, S.; Salem, D.; Gros, P. Role of IRF8 in immune cells functions, protection against infections, and susceptibility to inflammatory diseases. Hum. Genet. 2020, 139, 707–721. [Google Scholar] [CrossRef] [PubMed]
- Jiang, D.S.; Wei, X.; Zhang, X.F.; Liu, Y.; Zhang, Y.; Chen, K.; Gao, L.; Zhou, H.; Zhu, X.H.; Liu, P.P.; et al. IRF8 suppresses pathological cardiac remodelling by inhibiting calcineurin signalling. Nat. Commun. 2014, 5, 3303. [Google Scholar] [CrossRef] [PubMed]
- Shi, G.; Zhang, Z.; Ma, S.; Li, Y.; Du, S.; Chu, Y.; Li, Y.; Tang, X.; Yang, Y.; Chen, Z.; et al. Hepatic interferon regulatory factor 8 expression mediates liver ischemia/reperfusion injury in mice. Biochem. Pharmacol. 2021, 192, 114728. [Google Scholar] [CrossRef] [PubMed]
- Wu, H.; Li, Y.; Shi, G.; Du, S.; Wang, X.; Ye, W.; Zhang, Z.; Chu, Y.; Ma, S.; Wang, D.; et al. Hepatic interferon regulatory factor 8 expression suppresses hepatocellular carcinoma progression and enhances the response to anti–programmed cell death protein-1 therapy. Hepatology 2022, 76, 1602–1616. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.-A.; Zhang, R.; Jiang, D.; Deng, W.; Zhang, S.; Deng, S.; Zhong, J.; Wang, T.; Zhu, L.-H.; Yang, L.; et al. Interferon regulatory factor 9 protects against hepatic insulin resistance and steatosis in male mice. Hepatology 2013, 58, 603–616. [Google Scholar] [CrossRef] [PubMed]
- Wang, P.-X.; Zhang, R.; Huang, L.; Zhu, L.-H.; Jiang, D.-S.; Chen, H.-Z.; Zhang, Y.; Tian, S.; Zhang, X.-F.; Zhang, X.-D.; et al. Interferon regulatory factor 9 is a key mediator of hepatic ischemia/reperfusion injury. J. Hepatol. 2015, 62, 111–120. [Google Scholar] [CrossRef]
- Dhawan, T.; Zahoor, M.A.; Heryani, N.; Workenhe, S.T.; Nazli, A.; Kaushic, C. TRIM26 Facilitates HSV-2 Infection by Downregulating Antiviral Responses through the IRF3 Pathway. Viruses 2021, 13, 70. [Google Scholar] [CrossRef]
- Li, K.; Feng, Z.; Wang, L.; Ma, X.; Wang, L.; Liu, K.; Geng, X.; Peng, C. Chlorogenic Acid Alleviates Hepatic Ischemia–Reperfusion Injury by Inhibiting Oxidative Stress, Inflammation, and Mitochondria-Mediated Apoptosis In Vivo and In Vitro. Inflammation 2023, 46, 1061–1076. [Google Scholar] [CrossRef]
- Luo, J.; Li, J.; Li, T.; Zhang, Z.; Chen, G.; Li, Q.; Qi, H.; Si, Z.; Fan, Z. PIAS1 Alleviates Hepatic Ischemia-Reperfusion Injury in Mice through a Mechanism Involving NFATc1 SUMOylation. Dis. Markers 2022, 2022, 4988539. [Google Scholar] [CrossRef]
- Li, S.; He, J.; Xu, H.; Yang, J.; Luo, Y.; Song, W.; Qiao, B.; Zhang, H. Autophagic activation of IRF-1 aggravates hepatic ischemia–reperfusion injury via JNK signaling. MedComm 2021, 2, 91–100. [Google Scholar] [CrossRef]
- Yan, B.; Luo, J.; Kaltenmeier, C.; Du, Q.; Stolz, D.B.; Loughran, P.; Yan, Y.; Cui, X.; Geller, D.A. Interferon Regulatory Factor-1 (IRF1) activates autophagy to promote liver ischemia/reperfusion injury by inhibiting β-catenin in mice. PLoS ONE 2020, 15, e0239119. [Google Scholar] [CrossRef]
- Du, Q.; Luo, J.; Yang, M.-Q.; Liu, Q.; Heres, C.; Yan, Y.-H.; Stolz, D.; Geller, D.A. iNOS/NO is required for IRF1 activation in response to liver ischemia-reperfusion in mice. Mol. Med. 2020, 26, 56. [Google Scholar] [CrossRef]
- Cui, Z.; Li, S.; Liu, Z.; Zhang, Y.; Zhang, H. Interferon Regulatory Factor 1 Activates Autophagy to Aggravate Hepatic Ischemia-Reperfusion Injury by Increasing High Mobility Group Box 1 Release. Cell. Physiol. Biochem. 2018, 48, 328–338. [Google Scholar] [CrossRef]
- Yang, M.q.; Du, Q.; Goswami, J.; Varley, P.R.; Chen, B.; Wang, R.h.; Morelli, A.E.; Stolz, D.B.; Billiar, T.R.; Li, J.; et al. Interferon regulatory factor 1–Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury. Hepatology 2018, 67, 1056–1070. [Google Scholar] [CrossRef] [PubMed]
- Yu, Y.; Li, S.; Wang, Z.; He, J.; Ding, Y.; Zhang, H.; Yu, W.; Shi, Y.; Cui, Z.; Wang, X.; et al. Interferon regulatory factor-1 activates autophagy to aggravate hepatic ischemia-reperfusion injury via the P38/P62 pathway in mice. Sci. Rep. 2017, 7, 43684. [Google Scholar] [CrossRef] [PubMed]
- Yokota, S.; Yoshida, O.; Dou, L.; Spadaro, A.V.; Isse, K.; Ross, M.A.; Stolz, D.B.; Kimura, S.; Du, Q.; Demetris, A.J.; et al. IRF-1 Promotes Liver Transplant Ischemia/Reperfusion Injury via Hepatocyte IL-15/IL-15Rα Production. J. Immunol. 2015, 194, 6045–6056. [Google Scholar] [CrossRef]
- Cho, H.I.; Kim, K.M.; Kwak, J.H.; Lee, S.K.; Lee, S.M. Protective mechanism of anethole on hepatic ischemia/reperfusion injury in mice. J. Nat. Prod. 2013, 76, 1717–1723. [Google Scholar] [CrossRef] [PubMed]
- Loi, P.; Yuan, Q.; Torres, D.; Delbauve, S.; Laute, M.-A.; Lalmand, M.-C.; Pétein, M.; Goriely, S.; Goldman, M.; Flamand, V. Interferon regulatory factor 3 deficiency leads to interleukin-17-mediated liver ischemia-reperfusion injury. Hepatology 2013, 57, 351–361. [Google Scholar] [CrossRef]
- Nasiri, M.; Saadat, M.; Karimi, M.H.; Azarpira, N.; Saadat, I. Evaluating mRNA Expression Levels of the TLR4/IRF5 Signaling Axis during Hepatic Ischemia-Reperfusion Injuries. Exp. Clin. Transpl. Transplant. 2019, 17, 648–652. [Google Scholar] [CrossRef]
- Rani, R.; Kumar, S.; Sharma, A.; Mohanty, S.K.; Donnelly, B.; Tiao, G.M.; Gandhi, C.R. Mechanisms of concanavalin A-induced cytokine synthesis by hepatic stellate cells: Distinct roles of interferon regulatory factor-1 in liver injury. J. Biol. Chem. 2018, 293, 18466–18476. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Cheng, D.; Zhang, H.; Liu, Z.; Gao, M.; Wei, L.; Yan, F.; Li, C.; Wang, L.; Dong, G.; et al. Interleukin 28A aggravates Con A-induced acute liver injury by promoting the recruitment of M1 macrophages. FASEB J. 2024, 38, e23443. [Google Scholar] [CrossRef] [PubMed]
- Yan, F.; Cheng, D.; Wang, H.; Gao, M.; Zhang, J.; Cheng, H.; Wang, C.; Zhang, H.; Xiong, H. Corilagin Ameliorates Con A-Induced Hepatic Injury by Restricting M1 Macrophage Polarization. Front. Immunol. 2022, 12, 807509. [Google Scholar] [CrossRef] [PubMed]
- Li, B.; Lian, M.; Li, Y.; Qian, Q.; Zhang, J.; Liu, Q.; Tang, R.; Ma, X. Myeloid-Derived Suppressive Cells Deficient in Liver X Receptor α Protected from Autoimmune Hepatitis. Front. Immunol. 2021, 12, 732102. [Google Scholar] [CrossRef] [PubMed]
- Zhuang, Y.; Ortega-Ribera, M.; Thevkar Nagesh, P.; Joshi, R.; Huang, H.; Wang, Y.; Zivny, A.; Mehta, J.; Parikh, S.M.; Szabo, G. Bile acid-induced IRF3 phosphorylation mediates cell death, inflammatory responses, and fibrosis in cholestasis-induced liver and kidney injury via regulation of ZBP1. Hepatology 2024, 79, 752–767. [Google Scholar] [CrossRef] [PubMed]
- Li, H.; Chen, X.; Xu, J.; Zhu, L.; Li, C.; Sun, X.; Li, X.; Guo, J.; Li, J.; Wang, S.; et al. GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway. Hepatology 2024, 79, 392–408. [Google Scholar] [CrossRef] [PubMed]
- Liang, S.; Zhong, Z.; Kim, S.Y.; Uchiyama, R.; Roh, Y.S.; Matsushita, H.; Gottlieb, R.A.; Seki, E. Murine macrophage autophagy protects against alcohol-induced liver injury by degrading interferon regulatory factor 1 (IRF1) and removing damaged mitochondria. J. Biol. Chem. 2019, 294, 12359–12369. [Google Scholar] [CrossRef] [PubMed]
- Luther, J.; Khan, S.; Gala, M.K.; Kedrin, D.; Sridharan, G.; Goodman, R.P.; Garber, J.J.; Masia, R.; Diagacomo, E.; Adams, D.; et al. Hepatic gap junctions amplify alcohol liver injury by propagating cGAS-mediated IRF3 activation. Proc. Natl. Acad. Sci. USA 2020, 117, 11667–11673. [Google Scholar] [CrossRef]
- Sung, P.S.; Hong, S.-H.; Lee, J.; Park, S.-H.; Yoon, S.K.; Chung, W.J.; Shin, E.-C. CXCL10 is produced in hepatitis A virus-infected cells in an IRF3-dependent but IFN-independent manner. Sci. Rep. 2017, 7, 6387. [Google Scholar] [CrossRef]
- Tang, T.; Xu, T.; Liu, X.; Yang, T.; Zhang, L.; Yang, Z. Roles of BATF/JUN/IRF4 complex in tacrolimus mediated immunosuppression on Tfh cells in acute rejection after liver transplantation. J. Cell. Physiol. 2020, 236, 1776–1786. [Google Scholar] [CrossRef]
- Tang, T.; Lu, Q.; Yang, X.; Liu, X.; Liao, R.; Zhang, Y.; Yang, Z. Roles of the tacrolimus-dependent transcription factor IRF4 in acute rejection after liver transplantation. Int. Immunopharmacol. 2015, 28, 257–263. [Google Scholar] [CrossRef] [PubMed]
- Patel, S.J.; Liu, N.; Piaker, S.; Gulko, A.; Andrade, M.L.; Heyward, F.D.; Sermersheim, T.; Edinger, N.; Srinivasan, H.; Emont, M.P.; et al. Hepatic IRF3 fuels dysglycemia in obesity through direct regulation of Ppp2r1b. Sci. Transl. Med. 2022, 14, eabh3831. [Google Scholar] [CrossRef] [PubMed]
- Qiao, J.T.; Cui, C.; Qing, L.; Wang, L.S.; He, T.Y.; Yan, F.; Liu, F.Q.; Shen, Y.H.; Hou, X.G.; Chen, L. Activation of the STING-IRF3 pathway promotes hepatocyte inflammation, apoptosis and induces metabolic disorders in nonalcoholic fatty liver disease. Metabolism 2018, 81, 13–24. [Google Scholar] [CrossRef] [PubMed]
- Guo, S.; Feng, Y.; Zhu, X.; Zhang, X.; Wang, H.; Wang, R.; Zhang, Q.; Li, Y.; Ren, Y.; Gao, X.; et al. Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in nonalcoholic steatohepatitis. Nat. Commun. 2023, 14, 6047. [Google Scholar] [CrossRef] [PubMed]
- Lang, Z.; Yu, S.; Hu, Y.; Tao, Q.; Zhang, J.; Wang, H.; Zheng, L.; Yu, Z.; Zheng, J. Ginsenoside Rh2 promotes hepatic stellate cell ferroptosis and inactivation via regulation of IRF1-inhibited SLC7A11. Phytomedicine 2023, 118, 154950. [Google Scholar] [CrossRef] [PubMed]
- Oh, J.E.; Shim, K.Y.; Lee, J.I.; Choi, S.I.; Baik, S.K.; Eom, Y.W. 1-Methyl-L-tryptophan promotes the apoptosis of hepatic stellate cells arrested by interferon-γ by increasing the expression of IFN-γRβ, IRF-1 and FAS. Int. J. Mol. Med. 2017, 40, 576–582. [Google Scholar] [CrossRef] [PubMed]
- Iracheta-Vellve, A.; Petrasek, J.; Gyongyosi, B.; Satishchandran, A.; Lowe, P.; Kodys, K.; Catalano, D.; Calenda, C.D.; Kurt-Jones, E.A.; Fitzgerald, K.A.; et al. Endoplasmic Reticulum Stress-induced Hepatocellular Death Pathways Mediate Liver Injury and Fibrosis via Stimulator of Interferon Genes. J. Biol. Chem. 2016, 291, 26794–26805. [Google Scholar] [CrossRef] [PubMed]
- Yu, J.-H.; Choi, M.G.; Lee, N.Y.; Kwon, A.; Lee, E.; Koo, J.H. Hepatocyte GPCR signaling regulates IRF3 to control hepatic stellate cell transdifferentiation. Cell Commun. Signal. 2024, 22, 48. [Google Scholar] [CrossRef] [PubMed]
- Wu, Q.; Leng, X.; Zhang, Q.; Zhu, Y.Z.; Zhou, R.; Liu, Y.; Mei, C.; Zhang, D.; Liu, S.; Chen, S.; et al. IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis. Sci. Adv. 2024, 10, eadj2102. [Google Scholar] [CrossRef]
- Yu, M.; Xue, H.; Wang, Y.; Shen, Q.; Jiang, Q.; Zhang, X.; Li, K.; Jia, M.; Jia, J.; Xu, J.; et al. miR-345 inhibits tumor metastasis and EMT by targeting IRF1-mediated mTOR/STAT3/AKT pathway in hepatocellular carcinoma. Int. J. Oncol. 2017, 50, 975–983. [Google Scholar] [CrossRef]
- Wang, Z.; Pan, B.; Qiu, J.; Zhang, X.; Ke, X.; Shen, S.; Wu, X.; Yao, Y.; Tang, N. SUMOylated IL-33 in the nucleus stabilizes the transcription factor IRF1 in hepatocellular carcinoma cells to promote immune escape. Sci. Signal 2023, 16, eabq3362. [Google Scholar] [CrossRef]
- Yu, W.; He, J.; Wang, F.; He, Q.; Shi, Y.; Tao, X.; Sun, B. NR4A1 mediates NK-cell dysfunction in hepatocellular carcinoma via the IFN-γ/p-STAT1/IRF1 pathway. Immunology 2022, 169, 69–82. [Google Scholar] [CrossRef]
- Li, X.; Huang, J.; Wu, Q.; Du, Q.; Wang, Y.; Huang, Y.; Cai, X.; Geller, D.A.; Yan, Y. Inhibition of Checkpoint Kinase 1 (CHK1) Upregulates Interferon Regulatory Factor 1 (IRF1) to Promote Apoptosis and Activate Anti-Tumor Immunity via MICA in Hepatocellular Carcinoma (HCC). Cancers 2023, 15, 850. [Google Scholar] [CrossRef]
- Cui, X.; Zhao, H.; Wei, S.; Du, Q.; Dong, K.; Yan, Y.; Geller, D.A. Hepatocellular carcinoma-derived FOXO1 inhibits tumor progression by suppressing IL-6 secretion from macrophages. Neoplasia 2023, 40, 100900. [Google Scholar] [CrossRef]
- Yan, Y.; Zheng, L.; Du, Q.; Cui, X.; Dong, K.; Guo, Y.; Geller, D.A. Interferon regulatory factor 1 (IRF-1) downregulates Checkpoint kinase 1 (CHK1) through miR-195 to upregulate apoptosis and PD-L1 expression in Hepatocellular carcinoma (HCC) cells. Br. J. Cancer 2021, 125, 101–111. [Google Scholar] [CrossRef]
- Dong, K.; Du, Q.; Cui, X.; Wan, P.; Kaltenmeier, C.; Luo, J.; Yan, B.; Yan, Y.; Geller, D.A. MicroRNA-301a (miR-301a) is induced in hepatocellular carcinoma (HCC) and down- regulates the expression of interferon regulatory factor-1. Biochem. Biophys. Res. Commun. 2020, 524, 273–279. [Google Scholar] [CrossRef]
- Wan, P.Q.; Zhang, J.H.; Du, Q.; Dong, K.; Luo, J.; Heres, C.; Geller, D.A. Analysis of the relationship between microRNA-31 and interferon regulatory factor-1 in hepatocellular carcinoma cells. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 647–654. [Google Scholar] [CrossRef] [PubMed]
- Yan, Y.; Liang, Z.; Du, Q.; Yang, M.; Geller, D.A. MicroRNA-23a downregulates the expression of interferon regulatory factor-1 in hepatocellular carcinoma cells. Oncol. Rep. 2016, 36, 633–640. [Google Scholar] [CrossRef]
- Kim, G.W.; Imam, H.; Khan, M.; Mir, S.A.; Kim, S.J.; Yoon, S.K.; Hur, W.; Siddiqui, A. HBV-Induced Increased N6 Methyladenosine Modification of PTEN RNA Affects Innate Immunity and Contributes to HCC. Hepatology 2020, 73, 533–547. [Google Scholar] [CrossRef]
- Cevik, O.; Li, D.; Baljinnyam, E.; Manvar, D.; Pimenta, E.M.; Waris, G.; Barnes, B.J.; Kaushik-Basu, N. Interferon regulatory factor 5 (IRF5) suppresses hepatitis C virus (HCV) replication and HCV-associated hepatocellular carcinoma. J. Biol. Chem. 2017, 292, 21676–21689. [Google Scholar] [CrossRef]
- Fang, Y.; Lu, Z.H.; Liu, B.Z.; Li, N.; Yang, M.Z.; Wang, P. IRF5 promotes glycolysis in the progression of hepatocellular carcinoma and is regulated by TRIM35. J. Dig. Dis. 2023, 24, 480–490. [Google Scholar] [CrossRef] [PubMed]
- Feng, L.; Chen, X.; Li, P.; Li, Y.; Zhai, Y.; Liu, X.; Jin, Q.; Zhang, H.; Yu, C.; Xing, B.; et al. miR-424-3p promotes metastasis of hepatocellular carcinoma via targeting the SRF-STAT1/2 axis. Carcinogenesis 2023, 44, 610–625. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Zhu, J.; Guo, L.; Zou, Y.; Wang, F.; Shao, H.; Li, J.; Deng, X. Cholecystokinin protects mouse liver against ischemia and reperfusion injury. Int. Immunopharmacol. 2017, 48, 180–186. [Google Scholar] [CrossRef] [PubMed]
- Jiménez-Castro, M.B.; Cornide-Petronio, M.E.; Gracia-Sancho, J.; Peralta, C. Inflammasome-Mediated Inflammation in Liver Ischemia-Reperfusion Injury. Cells 2019, 8, 1131. [Google Scholar] [CrossRef] [PubMed]
- Gazia, C.; Lenci, I.; Manzia, T.M.; Martina, M.; Tisone, G.; Angelico, R.; Abenavoli, L.; Grassi, G.; Signorello, A.; Baiocchi, L. Current Strategies to Minimize Ischemia-Reperfusion Injury in Liver Transplantation: A Systematic Review. Rev. Recent. Clin. Trials 2021, 16, 372–380. [Google Scholar] [CrossRef] [PubMed]
- Elias-Miró, M.; Jiménez-Castro, M.B.; Rodés, J.; Peralta, C. Current knowledge on oxidative stress in hepatic ischemia/reperfusion. Free Radic. Res. 2013, 47, 555–568. [Google Scholar] [CrossRef] [PubMed]
- Kaltenmeier, C.; Wang, R.; Popp, B.; Geller, D.; Tohme, S.; Yazdani, H.O. Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury. Cells 2022, 11, 2222. [Google Scholar] [CrossRef] [PubMed]
- Lu, L.; Zhou, H.; Ni, M.; Wang, X.; Busuttil, R.; Kupiec-Weglinski, J.; Zhai, Y. Innate Immune Regulations and Liver Ischemia-Reperfusion Injury. Transplantation 2016, 100, 2601–2610. [Google Scholar] [CrossRef] [PubMed]
- Williams, J.A.; Ding, W.-X. Role of autophagy in alcohol and drug-induced liver injury. Food Chem. Toxicol. 2020, 136, 111075. [Google Scholar] [CrossRef]
- Lucey, M.R.; Mathurin, P.; Morgan, T.R. Alcoholic hepatitis. N. Engl. J. Med. 2009, 360, 2758–2769. [Google Scholar] [CrossRef]
- Gao, B.; Bataller, R. Alcoholic liver disease: Pathogenesis and new therapeutic targets. Gastroenterology 2011, 141, 1572–1585. [Google Scholar] [CrossRef]
- Gao, B.; Seki, E.; Brenner, D.A.; Friedman, S.; Cohen, J.I.; Nagy, L.; Szabo, G.; Zakhari, S. Innate immunity in alcoholic liver disease. Am. J. Physiol. Gastrointest. Liver Physiol. 2011, 300, G516–G525. [Google Scholar] [CrossRef]
- Petrasek, J.; Dolganiuc, A.; Csak, T.; Nath, B.; Hritz, I.; Kodys, K.; Catalano, D.; Kurt-Jones, E.; Mandrekar, P.; Szabo, G. Interferon regulatory factor 3 and type I interferons are protective in alcoholic liver injury in mice by way of crosstalk of parenchymal and myeloid cells. Hepatology 2011, 53, 649–660. [Google Scholar] [CrossRef]
- Sanz-Garcia, C.; Poulsen, K.L.; Bellos, D.; Wang, H.; McMullen, M.R.; Li, X.; Chattopadhyay, S.; Sen, G.; Nagy, L.E. The non-transcriptional activity of IRF3 modulates hepatic immune cell populations in acute-on-chronic ethanol administration in mice. J. Hepatol. 2019, 70, 974–984. [Google Scholar] [CrossRef] [PubMed]
- Gantner, F.; Leist, M.; Lohse, A.W.; Germann, P.G.; Tiegs, G. Concanavalin A-induced T-cell-mediated hepatic injury in mice: The role of tumor necrosis factor. Hepatology 1995, 21, 190–198. [Google Scholar] [CrossRef] [PubMed]
- Ibrahim, S.R.M.; Sirwi, A.; Eid, B.G.; Mohamed, S.G.A.; Mohamed, G.A. Summary of Natural Products Ameliorate Concanavalin A-Induced Liver Injury: Structures, Sources, Pharmacological Effects, and Mechanisms of Action. Plants 2021, 10, 228. [Google Scholar] [CrossRef]
- Wang, Y.; Meng, J.; Men, L.; An, B.; Jin, X.; He, W.; Lu, S.; Li, N. Rosmarinic Acid Protects Mice from Concanavalin A-Induced Hepatic Injury through AMPK Signaling. Biol. Pharm. Bull. 2020, 43, 1749–1759. [Google Scholar] [CrossRef]
- Sang, R.; Yu, Y.; Ge, B.; Xu, L.; Wang, Z.; Zhang, X. Taraxasterol from Taraxacum prevents concanavalin A-induced acute hepatic injury in mice via modulating TLRs/NF-κB and Bax/Bc1-2 signalling pathways. Artif. Cells Nanomed. Biotechnol. 2019, 47, 3929–3937. [Google Scholar] [CrossRef]
- Ye, X.J.; Xu, R.; Liu, S.Y.; Hu, B.; Shi, Z.J.; Shi, F.L.; Zeng, B.; Xu, L.H.; Huang, Y.T.; Chen, M.Y.; et al. Taraxasterol mitigates Con A-induced hepatitis in mice by suppressing interleukin-2 expression and its signaling in T lymphocytes. Int. Immunopharmacol. 2022, 102, 108380. [Google Scholar] [CrossRef]
- Shen, K.; Zheng, S.S.; Park, O.; Wang, H.; Sun, Z.; Gao, B. Activation of innate immunity (NK/IFN-gamma) in rat allogeneic liver transplantation: Contribution to liver injury and suppression of hepatocyte proliferation. Am. J. Physiol. Gastrointest. Liver Physiol. 2008, 294, G1070–G1077. [Google Scholar] [CrossRef]
- Janfeshan, S.; Yaghobi, R.; Eidi, A.; Karimi, M.H.; Geramizadeh, B.; Malekhosseini, S.A.; Kafilzadeh, F. Expression Profile of Interferon Regulatory Factor 1 in Chronic Hepatitis B Virus-Infected Liver Transplant Patients. Exp. Clin. Transpl. Transplant. 2017, 15, 669–675. [Google Scholar] [CrossRef]
- Zhao, W.; Zhang, Z.; Zhao, Q.; Liu, M.; Wang, Y. Inhibition of Interferon Regulatory Factor 4 Attenuates Acute Liver Allograft Rejection in Mice. Scand. J. Immunol. 2015, 82, 262–268. [Google Scholar] [CrossRef] [PubMed]
- Nehme, A.; Ghahramanpouri, M.; Ahmed, I.; Golsorkhi, M.; Thomas, N.; Munoz, K.; Abdipour, A.; Tang, X.; Wilson, S.M.; Wasnik, S.; et al. Combination therapy of insulin-like growth factor I and BTP-2 markedly improves lipopolysaccharide-induced liver injury in mice. FASEB J. 2022, 36, e22444. [Google Scholar] [CrossRef]
- You, N.; Chu, S.; Cai, B.; Gao, Y.; Hui, M.; Zhu, J.; Wang, M. Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the Toll-like receptor 4 signaling pathway. Front. Med. 2021, 15, 292–301. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; Zhuang, Z.j.; Bian, D.x.; Ma, X.j.; Xun, Y.h.; Yang, W.j.; Luo, Y.; Liu, Y.l.; Jia, L.; Wang, Y.; et al. Toll-like receptor-4 signalling in the progression of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet in mice. Clin. Exp. Pharmacol. Physiol. 2014, 41, 482–488. [Google Scholar] [CrossRef] [PubMed]
- Kanuri, G.; Ladurner, R.; Skibovskaya, J.; Spruss, A.; Königsrainer, A.; Bischoff, S.C.; Bergheim, I. Expression of toll-like receptors 1–5 but not TLR 6–10 is elevated in livers of patients with non-alcoholic fatty liver disease. Liver Int. 2014, 35, 562–568. [Google Scholar] [CrossRef] [PubMed]
- Talaat, R.M.; Elsayed, S.S.; Abdel-Hakem, N.E.; El-Shenawy, S.Z. Genetic Polymorphism in Toll-Like Receptor 3 and Interferon Regulatory Factor 3 in Hepatitis C Virus-Infected Patients: Correlation with Liver Cirrhosis. Viral Immunol. 2022, 35, 609–615. [Google Scholar] [CrossRef] [PubMed]
- Forner, A.; Reig, M.; Bruix, J. Hepatocellular carcinoma. Lancet 2018, 391, 1301–1314. [Google Scholar] [CrossRef] [PubMed]
- Craig, A.J.; von Felden, J.; Garcia-Lezana, T.; Sarcognato, S.; Villanueva, A. Tumour evolution in hepatocellular carcinoma. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 139–152. [Google Scholar] [CrossRef]
- Huang, A.; Yang, X.-R.; Chung, W.-Y.; Dennison, A.R.; Zhou, J. Targeted therapy for hepatocellular carcinoma. Signal Transduct. Target. Ther. 2020, 5, 146. [Google Scholar] [CrossRef]
- Yi, Y.; Wu, H.; Gao, Q.; He, H.W.; Li, Y.W.; Cai, X.Y.; Wang, J.X.; Zhou, J.; Cheng, Y.F.; Jin, J.J.; et al. Interferon regulatory factor (IRF)-1 and IRF-2 are associated with prognosis and tumor invasion in HCC. Ann. Surg. Oncol. 2013, 20, 267–276. [Google Scholar] [CrossRef] [PubMed]
- Yan, Y.; Zheng, L.; Du, Q.; Yan, B.; Geller, D.A. Interferon regulatory factor 1 (IRF-1) and IRF-2 regulate PD-L1 expression in hepatocellular carcinoma (HCC) cells. Cancer Immunol. Immunother. 2020, 69, 1891–1903. [Google Scholar] [CrossRef] [PubMed]
First Author | Publication Year | Disease | Model | Stimulation | State of IRFs | Involving Molecules | Signal Pathway | Effects |
---|---|---|---|---|---|---|---|---|
Nakano, R. [18] | 2024 | Hepatic Ischemia-Reperfusion Injury | mice | ApoE-/- | upregulation of IRF1 | IL-15 | - | Atherosclerosis can mirror intrahepatic immunity, particularly activating liver NK and T cells through IL-15 production, thereby exacerbating hepatic damage. The upregulation of IL-15 expression is associated with IRF1 overexpression. |
Li, K. [70] | 2023 | Hepatic Ischemia-Reperfusion Injury | Sprague-Dawley rat | Chlorogenic acid (CGA) | deregulation of IRF1 | HMGB1 | - | CGA pretreatment significantly decreased the levels of reactive oxygen species following HIRI, inhibited HMGB1 release by decreasing IRF1 expression, inhibited the expression of HMGB1, TLR-4, MyD88, P-IκB-α, NF-κB P65, and P-P65, and promoted IκB-α degradation. Thus, CGA appears to inhibit oxidative stress and inflammatory responses during HIRI. |
Luo, J. [71] | 2022 | Hepatic Ischemia-Reperfusion Injury | mice | PIAS1 | deregulation of IRF1 | p38 | PIAS1/NFATc1/HDAC1/IRF1/p38 MAPK | PIAS1 inactivated p38 MAPK signaling by inhibiting HDAC1-mediated IRF1 through NFATc1 SUMOylation, thereby repressing the inflammatory response and apoptosis of hepatocytes in vitro, and alleviating liver injury in vivo. |
Li, S. [72] | 2021 | Hepatic Ischemia-Reperfusion Injury | mice | - | upregulation of IRF1 | JNK, Beclin1 | IRF1/JNK | IRF1 is associated with JNK pathway activation followed by increases in Beclin1 protein levels. This JNK-induced autophagic cell death then leads to cell failure and plays an important role in liver function damage. |
Yan, B. [73] | 2020 | Hepatic Ischemia-Reperfusion Injury | mice | - | upregulation of IRF1 | β-catenin | - | IRF1-induced autophagy aggravates hepatic IR injury in part by inhibiting β-catenin. |
Du, Q. [74] | 2020 | Hepatic Ischemia-Reperfusion Injury | mice | iNOS/NO | upregulation of IRF1 | iNOS, PUMA, p21 | - | iNOS/NO-induced HDAC2 mediated histone H3 deacetylation and promoted IRF1 transcriptional activity. |
Klune, J.R. [21] | 2018 | Hepatic Ischemia-Reperfusion Injury | mice | IL-23 | upregulation of IRF1 | - | - | The overexpression of IL-23 in vivo through the use of an adenovirus vector also led to the expression of IL-17, CXCL2, IFN-γ, and IRF1. The increased expression of IL-23 also led to increased apoptosis in the liver. IL-23 is induced early by I/R in the liver. Its signaling leads to the activation of the IL-17/CXCL2 and IFN-γ/IRF1 pathways, resulting in increased apoptosis and necrosis. |
Cui, Z. [75] | 2018 | Hepatic Ischemia-Reperfusion Injury | mice | - | upregulation of IRF1 | HMGB1 | - | The levels of hepatic IRF1 mRNA and protein were significantly increased in livers after exposure to IRI, as well as an IRI-induced increase in HMGB1 mRNA and release of HMGB1 in liver tissue. IRF1 activates autophagy to aggravate hepatic IRI by increasing HMGB1 release. |
Yang, M.Q. [76] | 2018 | Hepatic Ischemia-Reperfusion Injury | mice | - | upregulation of IRF1 | Rab27a, extracellular vesicle, OxPL | - | IRF1 regulates Rab27a transcription and EV secretion, leading to OxPL activation of neutrophils and subsequent hepatic IR injury. |
Yu, Y. [77] | 2017 | Hepatic Ischemia-Reperfusion Injury | mice | - | upregulation of IRF1 | P38 | P38/P62 | IRF1 functioned as a trigger to activate autophagy via P38 activation and P62 was required for this P38-mediated autophagy. IRF1 appears to exert a pivotal role in hepatic IRI, by predisposing hepatocytes to activate an autophagic pathway. Such an effect promotes autophagic cell death through the P38/P62 pathway. |
Yokota, S. [78] | 2015 | Hepatic Ischemia-Reperfusion Injury | mice | - | upregulation of IRF1 | IL-15/IL-15Rα | - | IRF1 promotes liver transplantation (LTx) I/R injury via hepatocyte IL-15/IL-15Rα production which suggests that targeting IRF-1 and IL-15/IL-15Rα may be effective in reducing I/R injury associated with LTx. |
Castellaneta, A. [19] | 2014 | Hepatic Ischemia-Reperfusion Injury | mice | IFN-α | upregulation of IRF1 | Fas ligand, its receptor (Fas) and death receptor 5 | - | IFN-α derived from liver pDC plays a key role in the pathogenesis of liver I/R injury by enhancing apoptosis as a consequence of the induction of hepatocyte IRF1 expression. |
Cho, H.I. [79] | 2013 | Hepatic Ischemia-Reperfusion Injury | mice | anethole | deregulation of IRF1 | HMGB1/TLR | - | Anethole protects against hepatic I/R injury by the suppression of IRF1-mediated HMGB1 release and subsequent TLR activation. |
Ueki, S. [17] | 2010 | Hepatic Ischemia-Reperfusion Injury | mice | - | deregulation of IRF1 | caspase-8, IFN-γ | - | IRF1 deficiency in liver grafts, but not in recipients, resulted in a significant reduction in hepatocyte apoptosis and liver injury, as well as improved survival. Deficiency of IRF1 signaling in grafts resulted in significantly reduced messenger RNA (mRNA) levels for death ligands and death receptors in hepatocytes, as well as decreased caspase-8 activities, indicating that IRF1 mediates death ligand-induced hepatocyte death. |
Kim, K.H. [20] | 2009 | Hepatic Ischemia-Reperfusion Injury | Sprague-Dawley rat | - | upregulation of IRF1 | IFN-β, IFN-γ, IL-12, caspase-3 | - | Rats pretreated with AdIRF-1 before transplantation had elevated alanine aminotransferase levels and increased expression of IFN-β, IFN-γ, IL-12, and iNOS in the short-term period (3 h) when compared with donor livers pretreated with Adnull. |
Klune, J.R. [45] | 2012 | Hepatic Ischemia-Reperfusion Injury | mice | - | upregulation of IRF1 | IL-12, IFN-β, iNOS | - | IRF2 overexpression limits the production of IRF1-dependent proinflammatory genes, such as IL-12, IFNβ, and iNOS, even in the presence of IRF1 induction. Additionally, isograft liver transplantation with IRF2 heterozygote knockout (IRF2+/-) donor grafts that have reduced endogenous IRF2 levels results in worse injury following cold I/R during murine orthotopic liver transplantation. |
Loi, P. [80] | 2013 | Hepatic Ischemia-Reperfusion Injury | mice | - | deregulation of IRF3 | IL-27p35, IL-27p28 | IRF3/TLR4/IL-23/IL-17 | Quantification of cytokine gene expression revealed an increased liver expression of IL-12/IL-23p40, IL-23p19 mRNA, and IL-17A mRNA in IRF3-deficient versus wildtype mice, whereas IL-27p28 mRNA expression was diminished in the absence of IRF3. IRF3-dependent events downstream of TLR4 control the IL-23/IL-17 axis in the liver and this regulatory role of IRF3 is relevant to liver ischemia-reperfusion injury. |
Nasiri, M. [81] | 2019 | Hepatic Ischemia-Reperfusion Injury | mice | N-acetylcysteine | deregulation of IRF5 | - | - | Pretreatment with N-acetylcysteine significantly decreased the mRNA levels of TLR4/IRF5 and its downstream cytokines 3 h after reperfusion and subsequently improved the previously mentioned hepatic damages 168 h after reperfusion. |
Shi, G. [65] | 2021 | Hepatic Ischemia-Reperfusion Injury | mice | - | upregulation of IRF8 | CCXCL1, CXCL9, CCRL2 | - | IRF8 is up-regulated in the early hypnotic stage of IR. Upregulated IRF8 activates NF-κВ signaling pathway and promotes the release of autophagy-dependent or -independent chemokines, which in turn recruit massive neutrophils into the damaged liver sites, exacerbating hepatic I/R inflammatory injury. |
Wang, P.X. [68] | 2015 | Hepatic Ischemia-Reperfusion Injury | mice | - | upregulation of IRF9 | SIRT1, p53 | - | A deficiency in IRF9 markedly reduced the necrotic area, serum ALT, AST, immune cell infiltration, inflammatory cytokine levels, and hepatocyte apoptosis after liver I/R. IRF9 has a novel function of inducing hepatocyte apoptosis after I/R injury by decreasing SIRT1 expression and increasing acetyl-p53 levels. |
Rani, R. [82] | 2018 | Con A-Induced Hepatic Injury | mice | Con A | upregulation of IRF1 | SOD, JNK, caspase 3 | - | Con A binding to the mannose 6-phosphate receptor (Man-R) on HSCs induces JAK2 phosphorylation, which then phosphorylates STAT-1. The activated STAT1 translocates into the nucleus and induces IRF1 transcription. IRF1 produced this way stimulates IFNβ transcription. IFNβ protein released by HSCs binds to the IFNαβ receptor on hepatocytes and instigates JAK2/STAT1 activation, followed by IRF1 synthesis. IRF1 (through a currently unidentified mechanism) inhibits SOD expression leading to oxidative stress. Oxidative stress and IFNαβ stimulate JNK and caspase 3 activation, and cause apoptosis of hepatocytes. |
Zhang, J. [83] | 2024 | Con A-Induced Hepatic Injury | mice | IL-28A deletion | deregulation of IRF5 | IL-1β, IL-6, IL-12, TNF-α | - | IL-28A deletion plays an important protective role in the Con A-induced acute liver injury model and IL-28A deficiency inhibits the activation of M1 macrophages by inhibiting the NF-κB, MAPK, and IRF signaling pathways. |
Yan, F. [84] | 2022 | Con A-Induced Hepatic Injury | mice | Corilagin | deregulation of IRF5 | IL-6, IL-12, TNF-a, iNOS | - | Corilagin protects mice from Con A-induced immune-mediated hepatic injury by limiting M1 macrophage activation via the MAPK, NF-κB, and IRF signaling pathways, suggesting corilagin as a possible treatment choice for immune-mediated hepatic injury. |
Li, B. [85] | 2021 | Con A-Induced Hepatic Injury | mice | LXRa-/- | deregulation of IRF8 | - | - | Abrogation of LXRα facilitated the expansion of MDSCs by downregulating IRF8, thereby ameliorating hepatic immune injury profoundly. |
Zhuang, Y. [86] | 2024 | Cholestatic-Induced Hepatic Injury | mice | Bile acid | phosphorylation of IRF3 | ZBP1 | IRF3-ZBP1 | IRF3 knockout (IRF3-/-) mice showed significantly attenuated liver and kidney damage and fibrosis compared to wide-type mice after bile duct ligation. ZBP1 interacted with RIP1, RIP3, and NLRP3, thereby revealing its potential role in the regulation of cell-death and inflammation pathways. Bile acid-induced p-IRF3 and the IRF3-ZBP1 axis play a central role in the pathogenesis of cholestatic liver and kidney injury. |
Li, H. [87] | 2024 | Alcohol-Induced Hepatic Injury | mice | GRPR | upregulation of IRF1 | Caspase-1, NOX2 | - | The pro-inflammatory and oxidative stress roles of GRPR might be dependent on IRF1-mediated the Caspase-1 inflammasome and the NOX2-dependent reactive oxygen species pathway, respectively. |
Liang, S. [88] | 2019 | Alcohol-Induced Hepatic Injury | mice | p62 silencing or ATG7 deletion | upregulation of IRF1 | CCL5, CXCL10 | - | Macrophage autophagy protects against ALD by promoting IRF1 degradation and removal of damaged mitochondria, limiting macrophage activation and inflammation. Upon p62 silencing or ATG7 deletion, IRF1 starts to accumulate in autophagy-deficient macrophages and translocates into the nucleus, where it induces CCL5 and CXCL10 expression. |
Luther, J. [89] | 2020 | Alcohol-Induced Hepatic Injury | mice | Cx32 deletion | deregulation of IRF3 | IFNβ, IFIT2, IFIT3 | - | Disruption of Cx32 in ALD impaired IRF3-stimulated gene expression, resulting in decreased hepatic injury despite an increase in hepatic steatosis. |
Sung, P.S. [90] | 2017 | Hepatitis A-Induced Hepatic Injury | HAV-infected cells | - | deregulation of IRF3 | CXCL10 | - | CXCL10 production was reduced by silencing the expression of RIG-I-like receptor signal molecules, such as mitochondrial antiviral signaling proteins and IRF3, in HAV-infected cells. |
Tang, T. [91] | 2021 | Liver Transplantation-Induced Hepatic Injury | rats | Tacrolimus (TAC) | deregulation of IRF4 | IL-21 | BATF/JUN/IRF4 complex-IL-21 | TAC inhibited the expression of the BATF/JUN/IRF4 complex and interacted with the promoter of BATF and IRF4. The BATF/JUN/IRF4 complex participated in the inhibition of IL-21-producing Tfh cells after treatment with TAC. |
Tang, T. [92] | 2015 | Liver Transplantation-Induced Hepatic Injury | rats | TAC | deregulation of IRF4 | - | TAC-NFAT-IRF4 | TAC treatment prolonged the survival of liver allografts in recipients, significantly attenuating hepatic tissue injury and improving liver function. IRF4 expression in grafts was downregulated after TAC treatment. |
Patel, S.J. [93] | 2022 | Nonalcoholic Fatty Liver Disease | mice | HFD | upregulation of IRF3 | Ppp2r1b | IRF3-PPP2R1B | Global ablation of IRF3 in mice on a high-fat diet protects against both steatosis and dysglycemia, whereas hepatocyte-specific loss of IRF3 affects only dysglycemia. Integration of the IRF3-dependent transcriptome and cistrome in mouse hepatocytes identifies Ppp2r1b as a direct IRF3 target responsible for mediating its metabolic actions on glucose homeostasis. IRF3-mediated induction of Ppp2r1b amplified PP2A activity, with subsequent dephosphorylation of AMPKα and AKT. |
Qiao, J.T. [94] | 2018 | Nonalcoholic Fatty Liver Disease | L-O2 cell | Knocking down STING | deregulation of IRF3 | p-p65/p65, TNF-α, IL-6, and IL-1β | - | STING and IRF3 were upregulated in livers of HFD-fed mice and in FFA-induced L-O2 cells. Knocking down either STING or IRF3 led to a significant reduction in FFA-induced hepatic inflammation and apoptosis, as evidenced by the modulation of the NF-κB signaling pathway, inflammatory cytokines, and apoptotic signaling |
Guo, S. [95] | 2023 | Nonalcoholic Fatty Liver Disease | IRF4 knockout (F4MKO) mice | - | deregulation of IRF4 | FSTL1 | IRF4-FSTL1-DIP2A/CD14 | Skeletal muscle-specific IRF4 knockout (F4MKO) mice exhibited ameliorated hepatic steatosis, inflammation, and fibrosis, without changes in body weight, when put on a NASH diet. Dual luciferase assays showed that IRF4 can transcriptionally regulate FSTL1. Further, inducing FSTL1 expression in the muscles of F4MKO mice is sufficient to restore liver pathology. |
Tong, J. [59] | 2019 | Nonalcoholic Fatty Liver Disease | mice | HFD | deregulation of IRF6 | PPARγ | - | IRF6 is downregulated by the promoter, hypermethylation, upon metabolic stimulus exposure, which fails to inhibit Pparγ and its targets, driving abnormalities in lipid metabolism. |
Lang, Z. [96] | 2023 | Liver Fibrosis | mice | GRh2 | upregulation of IRF1 | SLC7A11 | - | GRh2 up-regulates IRF1 expression, resulting in the suppression of SLC7A11, which contributes to HSC ferroptosis and inactivation. GRh2 ameliorates liver fibrosis by enhancing HSC ferroptosis and inhibiting liver inflammation. GRh2 may be a promising drug for treating liver fibrosis. |
Oh, J.E. [97] | 2017 | Liver Fibrosis | HSCs | IFN-γ and 1-methyl-L-tryptophan (1-MT) | upregulation of IRF1 | - | - | IDO expression was markedly increased by IFN-γ through STAT1 activation and resulted in the depletion of tryptophan. This depletion induced G1 cell cycle arrest. When the cells were released from an IFN-γ-mediated G1 cell cycle arrest by treatment with 1-MT, the apoptosis of the HSCs was markedly increased through the induction of IFN-γRβ, IRF1, and FAS. |
Iracheta-Vellve, A. [98] | 2016 | Liver Fibrosis | mice | STING | phosphorylation of IRF3 | Caspase 3 | - | In CCl4-treated hepatocytes, ER stresses results of the phosphorylation of TBK1 via STING, followed by phosphorylation of IRF3. IRF3 associates with BAX in the mitochondria through its BH3-only domain, leading to pro-apoptotic caspase 3 activation and hepatocyte apoptosis. After chronic CCl4 administration, hepatocyte apoptosis is associated with secondary necrosis, which results in liver fibrosis. |
Yu, J.H. [99] | 2024 | Liver Fibrosis | mice | Gαs-coupled GPCR signaling | IRF3 phosphorylation | IL-33 | GPCR-IRF3-IL-33 | Gαs-coupled GPCR signaling increases IRF3 phosphorylation through cAMP-mediated activation of PKA. This leads to an increase in IL-33 expression, which further contributes to HSC activation. Hepatocyte GPCR signaling regulates IRF3 to control HSC trans-differentiation and provides insight for understanding the complex intercellular communication during liver fibrosis progression and suggests therapeutic opportunities for the disease. |
Wu, Q. [100] | 2024 | Liver Fibrosis | mice | STING | IRF3 phosphorylation | CDK4/6 | STING-IRF3-RB | The IRF3-RB interaction attenuates cyclin-dependent kinase 4/6 (CDK4/6)-mediated RB hyperphosphorylation that mobilizes RB to deactivate E2 family (E2F) transcription factors, thereby driving cells into senescence. STING-IRF3-RB signaling plays a notable role in HSCs within various murine models, pushing activated HSCs toward senescence. IRF3 global knockout or conditional deletion in HSCs aggravates liver fibrosis, a process mitigated by the CDK4/6 inhibitor. |
Alzaid, F. [56] | 2016 | Liver Fibrosis | mice | hepatocellular stress | upregulation of IRF5 | FasL, TNF, MHC II, IL6, and IL1β | - | IRF5-competent liver macrophages undergo proinflammatory activation in response to hepatocellular stress. Proinflammatory activation (M1) induces inflammatory a cytokine and death effector release that induces hepatocyte caspase (Casp)-dependent apoptosis. Activated factors include Fas ligand (FasL), TNF, MHC II, IL6, and IL1β. Proinflammatory activation induces type 1 and type 17 responses from CD4+T cells. Type 1 and 17 cytokines include IL17 and IFNγ. In IRF5-deficient macrophages, hepatocellular stress leads to immunosuppressive (MReg) polarization and secretion of IL10 and TGFβ. TGFβ expression induces differentiation of CD4+T cells into CD4+ FoxP3+ T cells, which contributes to IL-10 release. Secretion of IL-10 in IRF5 deficiency promotes anti-apoptotic signaling in hepatocytes mediated by B cell lymphoma 2 (BCL2) family members. This process maintains cell survival under stress. |
Yu, M. [101] | 2017 | Hepatocellular Carcinoma | HCC cells | miR-345 | deregulation of IRF1 | Slug, Snail and Twist | mTOR/STAT3/AKT | Over-expression of IRF1 mRNA was inversely correlated with the level of miR-345 in HCC specimens. Restoration of IRF1 resulted in promoted EMT and cell mobility in miR-345 overexpressing HCCLM3 cells. miR-345 acts as an inhibitor of the EMT process in HCC cells by targeting IRF1 and this study highlights the potential effects of miR-345 on prognosis and treatment of HCC. |
Wang, Z. [102] | 2023 | Hepatocellular Carcinoma | HCC cells | SUMOylated IL-33 | stabilized IRF1 | PD-L1, IL-8, CXCL1 | - | An increase in SUMOylated IL-33 in HCC cells in cocultures and in vivo-stabilized IRF1 and increased PD-L1 abundance and chemokine IL-8 secretion, which prevented the activation of cytotoxic T cells and promoted the M2 polarization of macrophages, respectively. |
Yu, W. [103] | 2023 | Hepatocellular Carcinoma | NK cell | NR4A1 | deregulation of IRF1 | - | IFN-γ/p-STAT1/IRF1 | NR4A1 was significantly highly expressed in tumor-infiltrating NK cells, which mediated the dysfunction of tumor-infiltrating NK cells by regulating the IFN-γ/p-STAT1/IRF1 signaling pathway, attenuated the anti-tumor function of NK cells, and reduced the efficacy of anti-PD-1 therapy. |
Li, X. [104] | 2023 | Hepatocellular Carcinoma | HCC cells | CHK1 | deregulation of IRF1 | MICA | IRF1-MICA | Overexpressed CHK1 suppresses IRF1 expression through proteolysis. Cisplatin and CHK1 inhibition upregulate MICA expression through IRF1-mediated transcriptional effects. DNA damage regulates the interaction of CHK1 and IRF1 to activate anti-tumor immunity via the IRF1-MICA pathway in HCC. |
Cui, X. [105] | 2023 | Hepatocellular Carcinoma | mice | FOXO1 | upregulation of IRF1 | CD206, IL-6, NO | - | These effects may be partially dependent on FOXO1 transcriptionally modulating the IRF-1/NO axis, exerting effects on macrophages and decreasing IL-6 release from macrophages in the tumor microenvironment indirectly. This feedback suppressed the progression of HCC by inactivating IL-6/STAT3 in HCC. |
Yan, Y. [106] | 2021 | Hepatocellular Carcinoma | HCC cells | IFN-γ | upregulation of IRF4 | miR-195, CHK1 | - | IRF1 induces miR-195 to suppress CHK1 protein expression, which induces apoptosis of HCC cells. IRF1 expression or CHK1 inhibition also upregulates PD-L1 expression via increased STAT3 phosphorylation. |
Yan, Y. [29] | 2021 | Hepatocellular Carcinoma | mice | - | upregulation of IRF1 | CXCL10/CXCR3 | IRF1/CXCL10/CXCR3 | IRF1 increased CD8+ T cells, NK and NKT cells migration, and activated IFN-γ secretion in NK and NKT cells to induce tumor apoptosis through the CXCL10/CXCR3 paracrine axis. |
Dong, K. [107] | 2020 | Hepatocellular Carcinoma | HCC cells | miR-301a | deregulation of IRF1 | - | - | Chronic hypoxia induces miR-301a in HCC in vitro and decreases IRF1 expression. Finally, miR-301a inhibition increases apoptosis and decreases HCC cell proliferation. |
Wan, P.Q. [108] | 2020 | Hepatocellular Carcinoma | HCC cells | miR-31 | deregulation of IRF1 | - | - | IRF1 was negatively correlated with miR-31 in HCC tissues and paired adjacent tissues. The expression level of miR-31 was inversely correlated with IRF1. MiR-31 inhibitor up-regulated the expression levels of IRF-1 in HuH7 cells, whereas the miR-31 mimic down-regulated the expression levels of IRF1. |
Yan, Y. [109] | 2016 | Hepatocellular Carcinoma | HCC cells | miR-23a | deregulation of IRF1 | - | - | MiR-23a mimics down-regulated IFNγ-induced IRF1 protein expression, while the miR-23a inhibitor increased IRF1. MiR-23a promotes HCC growth by downregulating IRF1. |
Kim, G.W. [110] | 2021 | Hepatocellular Carcinoma | HCC cells | PTEN | negative phosphorylation of IRF3 | PI3K/AKT | - | PTEN controlled IRF3 nuclear localization by negative phosphorylation of IRF3 at Ser97, and PTEN reduced carcinogenesis by inhibiting the PI3K/AKT pathway. |
Yuan, J. [48] | 2022 | Hepatocellular Carcinoma | HCC cells | - | upregulation of IRF4 | JAK2/STAT3 | - | In vitro experiments demonstrated that the overexpression of IRF4 inhibited the proliferation and migration capacity of HCC cells by restricting the JAK2/STAT3 signaling pathway and epithelial-mesenchymal transition. |
Cevik, O. [111] | 2017 | Hepatocellular Carcinoma | HCC cells | - | upregulation of IRF5 | HCV protein translation and RNA replication | - | IRF5 re-expression inhibited HCV protein translation and RNA replication. IRF5 re-expression induced apoptosis via loss in mitochondrial membrane potential, down-regulated autophagy, and inhibited hepatocyte cell migration/invasion. |
Fang, Y. [112] | 2023 | Hepatocellular Carcinoma | HCC cells | TRIM35 | deregulation of IRF5 | lactate dehydrogenase A (LDHA) | - | IRF5 was found to upregulate the expression of lactate dehydrogenase A (LDHA) and promote glycolysis. Tripartite motif containing 35 (TRIM35) interacted with IRF5, promoting its ubiquitination and degradation. These findings reveal the oncogenic function of IRF5 in the progression of HCC by enhancing glycolysis, further supporting the potential of IRF5 as a viable target for HCC therapy. |
Wu, H. [66] | 2022 | Hepatocellular Carcinoma | mice | - | upregulation of IRF8 | CCL20 | - | Overexpression of IRF8 in HCC cells significantly enhanced antitumor effects in immune-competent mice, modulating infiltration of tumor-associated macrophages (TAMs) and T cell exhaustion in tumor microenvironment. IRF8 regulated recruitment of TAMs by inhibiting the expression of CCL20. Adeno-associated virus 8-mediated hepatic IRF8 rescue significantly suppressed HCC progression and enhanced the response to anti-PD-1 therapy. |
Feng, L. [113] | 2023 | Hepatocellular Carcinoma | HCC cells | miR-424-3p | deregulation of IRF9 | ISG15, IFITM1, OASL, TRIM21 | SRF-STAT1/2/IRF9 | miR-424-3p reduces the interferon pathway by attenuating the transactivation of SRF on STAT1/2 and IRF9 genes, which in turn enhances the matrix metalloproteinases (MMPs)-mediated ECM remodeling. |
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Zeng, C.; Zhu, X.; Li, H.; Huang, Z.; Chen, M. The Role of Interferon Regulatory Factors in Liver Diseases. Int. J. Mol. Sci. 2024, 25, 6874. https://doi.org/10.3390/ijms25136874
Zeng C, Zhu X, Li H, Huang Z, Chen M. The Role of Interferon Regulatory Factors in Liver Diseases. International Journal of Molecular Sciences. 2024; 25(13):6874. https://doi.org/10.3390/ijms25136874
Chicago/Turabian StyleZeng, Chuanfei, Xiaoqin Zhu, Huan Li, Ziyin Huang, and Mingkai Chen. 2024. "The Role of Interferon Regulatory Factors in Liver Diseases" International Journal of Molecular Sciences 25, no. 13: 6874. https://doi.org/10.3390/ijms25136874