Role of Fibroblasts in Chronic Inflammatory Signalling in Chronic Rhinosinusitis with Nasal Polyps—A Systematic Review
Abstract
:1. Introduction
2. Methods
2.1. Research Questions and Eligibility Criteria
2.2. Search Strategy
2.3. Data Collection
2.4. Data Analysis
3. Results
3.1. Search Results
3.2. NPDF Cytokines
4. Discussion
4.1. Chemokine C-C Motif Ligand 5 (CCL5)
4.2. Eotaxins
4.3. Interleukin-4 (IL-4)
4.4. Interleukin-6 (IL-6) and (IL-8)
4.5. Interleukin-13 (IL-13)
4.6. Interleukin-17 (IL-17)
4.7. Interleukin-32 (IL-32)
4.8. CXC Motif Chemokine Ligand 10 (CXCL10)
4.9. Chemokine C-C Motif Ligand 2 (CCL2)
4.10. Chemokine C-C Motif Ligand 17 (CCL17)
4.11. Chemokine C-C Motif Ligand 20 (CCL20)
4.12. Thymic Stromal Lymphopoietin (TSLP)
4.13. Overall Effects of Cytokines Produced by NPDF in CRSwNP
5. Limitations
6. Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Criteria | Inclusion Criteria | Exclusion Criteria |
---|---|---|
Population | Patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) | All other diseases |
Intervention/Comparators | Stimulation of nasal-polyp-derived fibroblasts (NPDF) |
|
Outcomes | Cytokines and/or chemokines |
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Study Design |
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Language | Articles in English a | All non-English articles |
Author (Year) | Aim | Features of Patients | Previous Treatment | Control Group Fibroblasts | Stimulation by | ARN Detection | Immunoassay | Cytokine Produced | Outcome |
---|---|---|---|---|---|---|---|---|---|
Saji (2000) | To assess the production of RANTES cytokine by NPDF | No other associated disease | No comment | No | TNF-⍺ IL-1β | RT-PCR | ELISA | CCL5 (RANTES) | RANTES from NPDF was expressed after stimulation with TNF-⍺ and IL-1β |
Yamada (2001) | To assess if Syk is involved in the RANTES production | No comment | No comment | Nasal polyps | TNF-⍺ IL-1β | No | Western Blot | CCL5 (RANTES) | TNF-⍺ induced RANTES production in an independent manner at the Syk-expression level |
Liu (2002) | To evaluate the production of IL-6 and COX-2 by NPDF | No history of nasal allergy, asthma, or aspirin sensitivity | Not regular topical or oral medication within 3 weeks | Inferior turbinate mucosa | IL-1⍺ TNF-⍺ | Northern Blot in situ hybridization | No | IL-6 | IL-6 and COX-2 were expressed with a stimulatory effect of IL-1⍺ and TNF-⍺ |
Olsson (2003) | Proinflammatory functions of NPDF after PBMC mediators | No comment | Not anti-inflammatory treatment 2 weeks before | No | Dp-stimulated PBMC supernatants | No | Flow cytometry ELISA | Il-6 IL-8 | IL-6 and IL-8 were significantly higher in NPDFs cultured with Dp-stimulated PBMC supernatants compared to nonstimulated supernatants |
Yoshikawa (2003) | To assess the expression IL-13Rs | No comment | No comment | Lung and skin | TNF-⍺ IL-4 | RT-PCR | Flow cytometry ELISA | IL-13R⍺2 | TNF-⍺ and IL-4 upregulated the cell surface expression of IL-13R⍺2 in NPDF |
Steinke (2004) | To assess the effect of IL-4 and IL-13 on CysLT receptor expression on NPDF | No comment | No oral steroids or leukotriene modifier within 4 weeks | No | IL-4 IL-13 | RT-PCR | Flow cytometry | IL-6 CCL11 (eotaxin-1) TFG-β1 TFG-β2 | IL-4 induced changes in the mRNA and protein expression of fibrotic (TFG-β1, TFG-β2) and inflammatory cytokines and chemokines (IL-6 and CCL11) by NPDF |
Nonaka (2004) | To assess eotaxin production by NPDF | No comment | No comment | Uncinate process mucosa, lung and skin | IL-4 IL-13 TGF-β1 LPS | RT-PCR | ELISA | Eotaxin | LPS was necessary for IL-4 to strongly induce eotaxin in NPDF |
Shun (2005) | To assess CCL2 expression on NPDF | No history of nasal allergy, asthma, or aspirin sensitivity | Not regular topical or oral medication within 3 weeks | Inferior turbinate mucosa | TNF-⍺ | Northern Blot | Inmunohistochemistry | CCL2 (MCP-1) | CCL2 synthesis by NPDF may promote the macrophage recruitment |
Yoshifuku (2007) | To assess the expression of RANTES and eotaxin in NPDF |
| No treatment administered at least 2 weeks prior to surgery | Unstimulated cells of both groups | TNF-⍺ IL-4 | RT-PCR | ELISA | CCL5 (RANTES) eotaxin | Eotaxin had an important role in the selective recruitment of eosinophils in the eosinophilic group. |
Nonaka (2007) | To assess the production of MCP-4 by NPDF | No associated airway disease | No comment | No | IL-4 TLRs | RT-PCR | ELISA | CCL13 (MCP-4) | The induction of CCL13 by TLRs and IL-4 suggested an important role for NPDF in regulating eosinophilic infiltration |
Lin (2007) | To assess the CCL2 expression on NPDF | No history of nasal allergy, asthma, or aspirin sensitivity | No regular topical or oral medication within 3 weeks | Inferior turbinate mucosa | TNF-⍺ | Northern Blot | Western Blot | CCL2 (MCP-1) | TNF-α contributed to NP through the induction of CCL2 expression in NPDF |
Fukumoto (2008) | To assess if NPDF produced TARC | No comment | No comment | Uncinate process mucosa and lung | IL-4 LPS | RT-PCR | ELISA | CCL17 (TARC) | A combined stimulation with LPS and IL-4 induced CCL17 in NPDF |
Nonaka (2008) | To assess if NPDF produced TARC | Allergic chronic sinusitis but no associated lower airway disease | No comment | No | IL-4 TLRs | RT-PCR | ELISA | CCL17 (TARC) | A combined stimulation with TLR ligands and IL-4 induced TARC in NPDF |
Nonaka (2008) | To assess the expression of TARC by NPDF | Allergic chronic sinusitis | No comment | No | TNF-⍺ IL-4 poly I:C | RT-PCR | ELISA | CCL17 (TARC) | A combined stimulation with poly I:C, IL-4, and TNF-⍺ resulted in substantial amounts of TARC in NPDF |
Nonaka (2009) | To assess the expression of CCL20 by NPDF | Two atopic patients | No comment | No | TNF-α IL-4 IL-17 | RT-PCR | ELISA | CCL20 (MIP-3α) | IL-17A and IL-17E contributed to the infiltration of Th17 cells and DC through the production of CCL20 by NPDF |
Nonaka (2010) | To assess if NPDF produced CCL20 | 3 atopic patients, 2 of which with asthma | No comment | No | IL-1β TNF-α TLRs | RT-PCR | ELISA | CCL20 (MIP-3α) | NPDF recruiting DCs via the TLR/proinflammatory cytokine induced the production of CCL20 |
Nonaka (2010) | To assess the expression of TSLP on NPDF | No comment | No comment | No | IL-4 TNF-α IFN-ɣ IL-10 IL-13 | RT-PCR | ELISA | TSLP | TNF-α and Th2 cytokine (IL-4 or IL-13) synergistically induced TSLP for the development and regulation of Th2 cells |
Shun (2011) | Hypoxia activates NPDF which induce Cyr61, VEGF, and IL-8 | No history of nasal allergy, asthma, or aspirin sensitivity | No regular topical or oral medication within 3 weeks | No | Cyr61 | No | Inmunohistochemistry Western Blot ELISA | IL-8 | Under hypoxia, NPDF may induce VEGF and IL-8 |
Yoshikawa (2013) | To assess the expression of CXCL10 | 3 different groups of CRS patients:
| No comment | Middle turbinate mucosa and middle meatus mucosa | TNF-α IFN-ɣ IFN-β poly I:C | qRT-PCR | ELISA | CXCL10 | The ATA and AIA groups showed a significantly enhanced expression of CXCL 10 after poly IC |
Homma (2013) | To assess the level of cytokine and chemokine release from the NPDF and its effect on IL-17A |
| No systemic or topical corticosteroids or other immune-modulating drugs for at least 1 month before | Sphenoid mucosa | IL-17A | qRT-PCR | Cytokine assay system | IL-6 IL-8 IL-9 CCL2 (MCP-1) G-CSF | NPDF showed an enhanced basal secretion of MCP-1 and IL-17A stimulated secretion of IL-6, IL-9, and G-CSF. |
Niu (2014) | To assess the expression of IL-8 and CXCL1 by NPDF | No comment | Not regular topical or oral medication at least 1 month before | No | IL-17 | RT-PCR | No | CXCL1 IL-8 | NPDF produced CXCL1 and IL-8 which play a role in neutrophil recruitment |
Cho (2014) | To determine PGE2 effect on the levels of IL-6 and IL-8 | No comment | No comment | No | PGE2 | RT-PCR | Western blot ELISA | IL-6 IL-8 | PGE2 increased IL-6 expression via the EP2 and EP4 receptors and IL-8 expression via the EP4 receptor in NPDF |
Cho (2014) | To assess proinflammatory cytokines and MMPs | No history of allergy, asthma, or aspirin sensitivity | No oral antiallergic agents for at least 2 months | No | LPS | Microarray RT-PCR | Western blot ELISA | IL-6 IL-8 | LPS induced the production and expression of IL-6, IL-8, and MMPs in NPDF |
Shin (2016) | To assess the role of PPRs and TLRs in the production of cytokines by NPDF stimulated with airborne fungi | No history of allergy or asthma | No oral or topical medications at least 4 weeks before | No | Alternaria and Aspergillus | RT-PCR | ELISA | IL-6 IL-8 | Alternaria induced the production of IL-6 and IL-8 from NPDF, through the interaction of TLRs |
Shin (2016) | To assess if airborne fungi activate NPDF to produce TSLP | No history of allergy or asthma | No oral or topical medications at least 4 weeks before | No | Alternaria and Aspergillus | RT-PCR | No | TSLP | Fungi induced TSLP production by NPDF |
Cho (2016) | To investigate the mechanism of IL-32 expression induced by LPS in NPDF | No history of allergy, asthma, or aspirin sensitivity | No oral or topical medications during the previous 8 weeks before | Inferior turbinate mucosa | TNF-α IFN-ɣ TGF-β1 IL-1β LPS | RT-PCR | Western blot | IL-32 | LPS induced IL-32 expression in NPDF through the TLR4-JNK-AKT-CREB signalling pathway |
Shimizu (2017) | To assess if coagulation factors can produce the release of cytokines and extracellular matrix proteins from NPDF | No comment | No comment | No | Thrombin FXa PAR agonist peptides | RT-PCR | Inmunoassay kit | TGF-β1 CCL11(eotaxin-1) IL-6 IL-8 | Coagulation factors induced the release of cytokines and ECM protein by NPDF |
Imoto (2022) | To assess if leptin release is related to severity of eosinophilic CRSwNP | Eosinophilic CRSwNP | No oral steroids intake for at least 4 weeks before | No CRS | Leptin IL-4 IL-13 | RT-PCR | Western blot ELISA | CCL26 (eotaxin-3) | Leptin significantly augmented eotaxin-3 expression in NPDF |
Cheng (2022) | To assess the role of IL-17 in pathogenesis od CRSwNP | No comment | No nasal decongestants or antihistamines were administered for 4 weeks before | Untreated fibroblasts | TNF-α | RT-PCR | Western blot ELISA | IL-17A | TNF-α increased levels of IL-17A in NPDF through the PI3K/Akt/HIF-1 α pathway |
Lee (2022) | To assess the inflammatory effects of PM10 in NPDF | No comment | No oral or nasal corticosteroids or antibiotics for 4 weeks before | No | PM10 | RT-PCR | Western blot ELISA | IL-4 IL-6 IL-33 CXCL1 | Increased expression of IL-6, IL-4, IL-33, and CXCL1 on PM10-treated human NPDF |
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Palacios-García, J.; Porras-González, C.; Moreno-Luna, R.; Maza-Solano, J.; Polo-Padillo, J.; Muñoz-Bravo, J.L.; Sánchez-Gómez, S. Role of Fibroblasts in Chronic Inflammatory Signalling in Chronic Rhinosinusitis with Nasal Polyps—A Systematic Review. J. Clin. Med. 2023, 12, 3280. https://doi.org/10.3390/jcm12093280
Palacios-García J, Porras-González C, Moreno-Luna R, Maza-Solano J, Polo-Padillo J, Muñoz-Bravo JL, Sánchez-Gómez S. Role of Fibroblasts in Chronic Inflammatory Signalling in Chronic Rhinosinusitis with Nasal Polyps—A Systematic Review. Journal of Clinical Medicine. 2023; 12(9):3280. https://doi.org/10.3390/jcm12093280
Chicago/Turabian StylePalacios-García, José, Cristina Porras-González, Ramón Moreno-Luna, Juan Maza-Solano, Juan Polo-Padillo, José Luis Muñoz-Bravo, and Serafín Sánchez-Gómez. 2023. "Role of Fibroblasts in Chronic Inflammatory Signalling in Chronic Rhinosinusitis with Nasal Polyps—A Systematic Review" Journal of Clinical Medicine 12, no. 9: 3280. https://doi.org/10.3390/jcm12093280