IL-1-IL-17 Signaling Axis Contributes to Fibrosis and Inflammation in Two Different Murine Models of Systemic Sclerosis
Open accessAbstract
OBJECTIVE: Systemic sclerosis (SSc) is a progressive fibrotic disease that affects the skin and internal organs. Despite evidence implicating increased interleukin-17 (IL-17) activity in SSc, the role of IL-17 in SSc remains uncertain. The purpose of this study was to investigate whether IL-17 plays a pathophysiological role in SSc in two different murine models of SSc. METHODS: Bleomycin (BLM)-induced fibrosis and chronic graft-versus-host disease (cGVHD) models were used. Histological analysis was performed using Masson's trichrome and immunohistochemical staining. Quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunoassays were used to quantify the messenger RNA and protein levels of inflammatory mediators in dermal fibroblasts. RESULTS: experiments showed that IL-1 and IL-17 exerted synergistic effects on the expression of profibrotic and inflammatory mediators. In the cGVHD model, C57BL/6 mice receiving splenocytes of IL-1Ra-KO BALB/c mice developed more severe cGVHD than did those receiving cells from WT mice. Knockdown of IL-17 in IL-1Ra-KO donor mice significantly attenuated the IL-1-induced acceleration of cGVHD severity. CONCLUSION: Targeting IL-1 and its downstream IL-17 activity may be a novel treatment strategy for inhibiting inflammation and tissue fibrosis in SSc.
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IL-17A promotes TGF-β production.
“In addition to promoting TGF-β production116,119”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [119]
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Fibrosis: from mechanisms to medicines
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- Authors
- Park, M.-J., Moon, S.-J., Lee, E.-J., Jung, K.-A., Kim, E.-K., Kim, D.-S., Lee, J.-H., Kwok, S.-K., Min, J.-K., Park, S.-H., & Cho, M.-L.
- Affiliations
- Catholic University of Korea (KR)
- Corresponding author
- Park, Sung-Hwan
- Cho, Mi-La
- ORCID
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2018-07-10
- Volume
- 9
- Pages
- 1611-1611
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC6048384
- OpenAlex
- W2810227809
- Cited by
- 89
- References
- 48
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 27 · 2021: 9 · 2020: 18 · 2019: 9
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Korea Health Industry Development Institute (HI15C1062)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Rheumatology › Dupuytren's Contracture and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- systemic sclerosis, interleukin-1, IL-17, IL-17 signaling, fibrosis, chronic graft-versus-host disease, bleomycin-induced fibrosis, dermal fibroblasts, interleukin-1 receptor antagonist, inflammation, mouse model, therapeutic target
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