Microbe-Derived Antioxidants Reduce Lipopolysaccharide-Induced Inflammatory Responses by Activating the Nrf2 Pathway to Inhibit the ROS/NLRP3/IL-1β Signaling Pathway
Abstract
:1. Introduction
2. Results
2.1. MA Exhibits Anti-Inflammatory Effects in LPS-Induced RAW264.7 Cells
2.2. MA Attenuates LPS-Induced Inflammatory Effects by Inhibiting NLRP3
2.3. MA Mitigates LPS-Induced Oxidative Stress in RAW264.7 Cells
2.4. MA Inhibits LPS-Induced Cellular Inflammation through Activation of the Nrf2/NLRP3/IL-1β Signaling Pathway
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Cell Culture and Processing
4.3. Cell Viability Assay
4.4. Inflammatory Cytokine Detection
4.5. Measurement of Intracellular ROS
4.6. Determination of Antioxidant Enzyme Activity
4.7. Reverese Transcription-Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR)
4.8. Western Blot Analysis
4.9. RNA Silencing
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Schett, G.; Neurath, M.F. Resolution of chronic inflammatory disease: Universal and tissue-specific concepts. Nat. Commun. 2018, 9, 3261. [Google Scholar] [CrossRef] [PubMed]
- Salas, A.; Hernandez-Rocha, C.; Duijvestein, M.; Faubion, W.; McGovern, D.; Vermeire, S.; Vetrano, S.; Vande Casteele, N. JAK-STAT pathway targeting for the treatment of inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 323–337. [Google Scholar] [CrossRef] [PubMed]
- Liberale, L.; Montecucco, F.; Tardif, J.C.; Libby, P.; Camici, G.G. Inflamm-ageing: The role of inflammation in age-dependent cardiovascular disease. Eur. Heart J. 2020, 41, 2974–2982. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.; Bozec, A.; Ramming, A.; Schett, G. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nat. Rev. Rheumatol. 2019, 15, 9–17. [Google Scholar] [CrossRef]
- Hseu, Y.C.; Tseng, Y.F.; Pandey, S.; Shrestha, S.; Lin, K.Y.; Lin, C.W.; Lee, C.C.; Huang, S.T.; Yang, H.L. Coenzyme Q0 Inhibits NLRP3 Inflammasome Activation through Mitophagy Induction in LPS/ATP-Stimulated Macrophages. Oxid. Med. Cell. Longev. 2022, 2022, 4266214. [Google Scholar] [CrossRef] [PubMed]
- Xie, C.; Ge, M.; Jin, J.; Xu, H.; Mao, L.; Geng, S.; Wu, J.; Zhu, J.; Li, X.; Zhong, C. Mechanism investigation on Bisphenol S-induced oxidative stress and inflammation in murine RAW264.7 cells: The role of NLRP3 inflammasome, TLR4, Nrf2 and MAPK. J. Hazard. Mater. 2020, 394, 122549. [Google Scholar] [CrossRef]
- Xie, Z.; Wang, Y.; Huang, J.; Qian, N.; Shen, G.; Chen, L. Anti-inflammatory activity of polysaccharides from Phellinus linteus by regulating the NF-kappaB translocation in LPS-stimulated RAW264.7 macrophages. Int. J. Biol. Macromol. 2019, 129, 61–67. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.B.; Yang, F.; Wang, Y.; Jiao, F.Z.; Zhang, H.Y.; Wang, L.W.; Gong, Z.J. Inhibition of HDAC6 attenuates LPS-induced inflammation in macrophages by regulating oxidative stress and suppressing the TLR4-MAPK/NF-kappaB pathways. Biomed. Pharmacother. 2019, 117, 109166. [Google Scholar] [CrossRef] [PubMed]
- Tschopp, J.; Schroder, K. NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production? Nat. Rev. Immunol. 2010, 10, 210–215. [Google Scholar] [CrossRef] [PubMed]
- Swanson, K.V.; Deng, M.; Ting, J.P. The NLRP3 inflammasome: Molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 2019, 19, 477–489. [Google Scholar] [CrossRef] [PubMed]
- Dai, Y.; Zhang, J.; Xiang, J.; Li, Y.; Wu, D.; Xu, J. Calcitriol inhibits ROS-NLRP3-IL-1beta signaling axis via activation of Nrf2-antioxidant signaling in hyperosmotic stress stimulated human corneal epithelial cells. Redox Biol. 2019, 21, 101093. [Google Scholar] [CrossRef] [PubMed]
- Tonelli, C.; Chio, I.I.C.; Tuveson, D.A. Transcriptional Regulation by Nrf2. Antioxid. Redox Signal. 2018, 29, 1727–1745. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lefaki, M.; Papaevgeniou, N.; Chondrogianni, N. Redox regulation of proteasome function. Redox Biol. 2017, 13, 452–458. [Google Scholar] [CrossRef] [PubMed]
- Cao, J.; Lu, M.; Yan, W.; Li, L.; Ma, H. Dehydroepiandrosterone alleviates intestinal inflammatory damage via GPR30-mediated Nrf2 activation and NLRP3 inflammasome inhibition in colitis mice. Free Radic. Biol. Med. 2021, 172, 386–402. [Google Scholar] [CrossRef]
- Xu, J.J.; Gong, L.L.; Li, Y.Y.; Zhou, Z.B.; Yang, W.W.; Wan, C.X.; Zhang, W.N. Anti-inflammatory effect of a polysaccharide fraction from Craterellus cornucopioides in LPS-stimulated macrophages. J. Food Biochem. 2021, 45, e13842. [Google Scholar] [CrossRef]
- Ciesarova, Z.; Murkovic, M.; Cejpek, K.; Kreps, F.; Tobolkova, B.; Koplik, R.; Belajova, E.; Kukurova, K.; Dasko, L.; Panovska, Z.; et al. Why is sea buckthorn (Hippophae rhamnoides L.) so exceptional? A review. Food Res. Int. 2020, 133, 109170. [Google Scholar] [CrossRef]
- Wang, L.T.; Lv, M.J.; An, J.Y.; Fan, X.H.; Dong, M.Z.; Zhang, S.D.; Wang, J.D.; Wang, Y.Q.; Cai, Z.H.; Fu, Y.J. Botanical characteristics, phytochemistry and related biological activities of Rosa roxburghii Tratt fruit, and its potential use in functional foods: A review. Food Funct. 2021, 12, 1432–1451. [Google Scholar] [CrossRef]
- Luo, Z.; Gao, Q.; Zhang, H.; Zhang, Y.; Zhou, S.; Zhang, J.; Xu, W.; Xu, J. Microbe-derived antioxidants attenuate cobalt chloride-induced mitochondrial function, autophagy and BNIP3-dependent mitophagy pathways in BRL3A cells. Ecotoxicol. Environ. Saf. 2022, 232, 113219. [Google Scholar] [CrossRef]
- Cai, X.; Chen, X.; Yang, F.; Xu, J.; Gu, J.; Zhang, C. A Preliminary Research of Antioxidant Capacity by Micro-Derived Antioxidants in vitro. Biotechnology 2011, 21, 84–87. [Google Scholar]
- Zhu, L.H. Impact of weaning and an antioxidant blend on intestinal barrier function and antioxidant status in pigs (vol 90, pg 2581, 2012). J. Anim. Sci. 2013, 91, 1522. [Google Scholar]
- Luo, Z.; Xu, X.; Zhao, S.; Sho, T.; Luo, W.; Zhang, J.; Xu, W.; Hon, K.; Xu, J. Inclusion of microbe-derived antioxidant during pregnancy and lactation attenuates high-fat diet-induced hepatic oxidative stress, lipid disorders, and NLRP3 inflammasome in mother rats and offspring. Food Nutr. Res. 2019, 63, 3504. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moore, K.J.; Tabas, I. Macrophages in the pathogenesis of atherosclerosis. Cell 2011, 145, 341–355. [Google Scholar] [CrossRef] [PubMed]
- Jenkins, S.J.; Ruckerl, D.; Cook, P.C.; Jones, L.H.; Finkelman, F.D.; van Rooijen, N.; MacDonald, A.S.; Allen, J.E. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science 2011, 332, 1284–1288. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Coll, R.C.; Robertson, A.A.; Chae, J.J.; Higgins, S.C.; Munoz-Planillo, R.; Inserra, M.C.; Vetter, I.; Dungan, L.S.; Monks, B.G.; Stutz, A.; et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 2015, 21, 248–255. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abderrazak, A.; Syrovets, T.; Couchie, D.; El Hadri, K.; Friguet, B.; Simmet, T.; Rouis, M. NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol. 2015, 4, 296–307. [Google Scholar] [CrossRef]
- Xu, Y.; Yuan, Q.; Cao, S.; Cui, S.; Xue, L.; Song, X.; Li, Z.; Xu, R.; Yuan, Q.; Li, R. Aldehyde dehydrogenase 2 inhibited oxidized LDL-induced NLRP3 inflammasome priming and activation via attenuating oxidative stress. Biochem. Biophys Res. Commun. 2020, 529, 998–1004. [Google Scholar] [CrossRef]
- Back, M.; Yurdagul, A., Jr.; Tabas, I.; Oorni, K.; Kovanen, P.T. Inflammation and its resolution in atherosclerosis: Mediators and therapeutic opportunities. Nat. Rev. Cardiol. 2019, 16, 389–406. [Google Scholar] [CrossRef]
- Long, Y.; Liu, X.; Tan, X.Z.; Jiang, C.X.; Chen, S.W.; Liang, G.N.; He, X.M.; Wu, J.; Chen, T.; Xu, Y. ROS-induced NLRP3 inflammasome priming and activation mediate PCB 118- induced pyroptosis in endothelial cells. Ecotoxicol. Environ. Saf. 2020, 189, 109937. [Google Scholar] [CrossRef]
- Zhang, X.-N.; Zhao, N.; Guo, F.-F.; Wang, Y.-R.; Liu, S.-X.; Zeng, T. Diallyl disulfide suppresses the lipopolysaccharide-driven inflammatory response of macrophages by activating the Nrf2 pathway. Food Chem. Toxicol. 2022, 159, 112760. [Google Scholar] [CrossRef]
- Li, S.; Zheng, L.; Zhang, J.; Liu, X.; Wu, Z. Inhibition of ferroptosis by up-regulating Nrf2 delayed the progression of diabetic nephropathy. Free Radic. Biol. Med. 2021, 162, 435–449. [Google Scholar] [CrossRef]
- Ren, J.; Su, D.; Li, L.; Cai, H.; Zhang, M.; Zhai, J.; Li, M.; Wu, X.; Hu, K. Anti-inflammatory effects of Aureusidin in LPS-stimulated RAW264.7 macrophages via suppressing NF-kappaB and activating ROS- and MAPKs-dependent Nrf2/HO-1 signaling pathways. Toxicol. Appl. Pharmacol. 2020, 387, 114846. [Google Scholar] [CrossRef] [PubMed]
- Luo, J.F.; Shen, X.Y.; Lio, C.K.; Dai, Y.; Cheng, C.S.; Liu, J.X.; Yao, Y.D.; Yu, Y.; Xie, Y.; Luo, P.; et al. Activation of Nrf2/HO-1 Pathway by Nardochinoid C Inhibits Inflammation and Oxidative Stress in Lipopolysaccharide-Stimulated Macrophages. Front. Pharmacol. 2018, 9, 911. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bao, L.; Li, J.; Zha, D.; Zhang, L.; Gao, P.; Yao, T.; Wu, X. Chlorogenic acid prevents diabetic nephropathy by inhibiting oxidative stress and inflammation through modulation of the Nrf2/HO-1 and NF-kB pathways. Int. Immunopharmacol. 2018, 54, 245–253. [Google Scholar] [CrossRef] [PubMed]
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Shen, C.; Luo, Z.; Ma, S.; Yu, C.; Gao, Q.; Zhang, M.; Zhang, H.; Zhang, J.; Xu, W.; Yao, J.; et al. Microbe-Derived Antioxidants Reduce Lipopolysaccharide-Induced Inflammatory Responses by Activating the Nrf2 Pathway to Inhibit the ROS/NLRP3/IL-1β Signaling Pathway. Int. J. Mol. Sci. 2022, 23, 12477. https://doi.org/10.3390/ijms232012477
Shen C, Luo Z, Ma S, Yu C, Gao Q, Zhang M, Zhang H, Zhang J, Xu W, Yao J, et al. Microbe-Derived Antioxidants Reduce Lipopolysaccharide-Induced Inflammatory Responses by Activating the Nrf2 Pathway to Inhibit the ROS/NLRP3/IL-1β Signaling Pathway. International Journal of Molecular Sciences. 2022; 23(20):12477. https://doi.org/10.3390/ijms232012477
Chicago/Turabian StyleShen, Cheng, Zhen Luo, Sheng Ma, Chengbing Yu, Qingying Gao, Meijuan Zhang, Hongcai Zhang, Jing Zhang, Weina Xu, Jianbo Yao, and et al. 2022. "Microbe-Derived Antioxidants Reduce Lipopolysaccharide-Induced Inflammatory Responses by Activating the Nrf2 Pathway to Inhibit the ROS/NLRP3/IL-1β Signaling Pathway" International Journal of Molecular Sciences 23, no. 20: 12477. https://doi.org/10.3390/ijms232012477