Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25697137
DOI
10.1016/j.cyto.2015.01.019
PII: S1043-4666(15)00038-1
Knihovny.cz E-zdroje
- Klíčová slova
- Inflammation, Interleukin-35, Rheumatoid arthritis, Synovial tissue,
- MeSH
- fibroblasty účinky léků metabolismus MeSH
- interleukiny metabolismus MeSH
- leukocyty mononukleární účinky léků metabolismus MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- myši MeSH
- podjednotky proteinů metabolismus MeSH
- psoriatická artritida metabolismus patologie MeSH
- revmatoidní artritida metabolismus patologie MeSH
- synoviální membrána patologie MeSH
- TNF-alfa farmakologie MeSH
- up regulace účinky léků genetika MeSH
- vedlejší histokompatibilní antigeny MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- EBI3 protein, human MeSH Prohlížeč
- interleukin-35, human MeSH Prohlížeč
- interleukiny MeSH
- mediátory zánětu MeSH
- podjednotky proteinů MeSH
- TNF-alfa MeSH
- vedlejší histokompatibilní antigeny 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.
Citace poskytuje Crossref.org
