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Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis
M. Filková, Z. Vernerová, H. Hulejová, K. Prajzlerová, D. Veigl, K. Pavelka, J. Vencovský, L. Šenolt,
Language English Country England, Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT12440
MZ0
CEP Register
- MeSH
- Fibroblasts drug effects metabolism MeSH
- Interleukins metabolism MeSH
- Leukocytes, Mononuclear drug effects metabolism MeSH
- Humans MeSH
- Inflammation Mediators metabolism MeSH
- Mice MeSH
- Protein Subunits metabolism MeSH
- Arthritis, Psoriatic metabolism pathology MeSH
- Arthritis, Rheumatoid metabolism pathology MeSH
- Synovial Membrane pathology MeSH
- Tumor Necrosis Factor-alpha pharmacology MeSH
- Up-Regulation drug effects genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
OBJECTIVE: Interleukin-35 (IL-35) is a heterodimeric member of the IL-12 family consisting of p35/IL-12a and EBI3/IL-27b subunits. Expressed in murine Treg cells, IL-35 controls inflammatory diseases in mouse models. However, human IL-35 is expressed in Teff cells rather than in Treg cells and is shown to be upregulated under inflammatory conditions. Our aim was to examine the involvement of IL-35 in the pathogenesis of rheumatoid arthritis (RA). METHODS: Immunohistochemical and immunofluorescence analysis was used to determine the expression and localization of IL-35 and its subunits (p35/EBI3) and IL-35 receptor (IL12Rβ2/gp130) in RA, osteoarthritis (OA) and psoriatic arthritis (PsA) synovial tissues. Expression of p35/EBI3 subunits and release of inflammatory cytokines upon stimulation with IL-35 were assessed in RA synovial fibroblasts (SFs) and peripheral blood mononuclear cells (PBMCs). RESULTS: Both IL-35 and its subunits were upregulated in RA in comparison with OA or PsA synovium. Using cell-specific markers, p35 and EBI3 were identified in macrophages, dendritic cells, SFs, and T as well as B cells in RA synovium. Both p35 and EBI3 were induced by TNFα in RASFs and PBMCs. IL-35 dose-dependently upregulated release of pro-inflammatory mediators IL-1β, IL-6 and MCP-1 in PBMCs. While gp130 receptor subunit was upregulated in RA synovium and was expressed in RASFs and PBMCs, there was no difference in IL12Rβ2 expression subunit among tissues and its presence in RASFs was lacking. CONCLUSION: Upregulation of IL-35 at sites of inflammation in RA and its pro-inflammatory potential suggests that IL-35 might play an important role in RA pathogenesis.
References provided by Crossref.org
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