Artikel
CXCL17 is inducible by INF-γ and inhibits angiogenesis in rheumatoid arthritis
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Veröffentlicht: | 8. Oktober 2019 |
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Gliederung
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Background: CXCL17 is known to attract monocytes and was detected in autoimmune diseases such as idiopathic lung fibrosis and Sjögren’s syndrome so far. Our aim was to study the role of the recently discovered cytokine CXCL17 and its receptor G-protein coupled receptor 35 (GPR35) in rheumatoid arthritis (RA).
Methods: CXCL17/GPR35 immunohistochemistry and in-situ-hybridization/immunofluorescence double-stainings were performed on synovial tissue from joint replacements of RA and osteoarthritis (OA) patients. CXCL17 production of cultured synovial fibroblasts and smooth muscle cells was quantified by qPCR and ELISA after stimulation with TNF-α, INF-γ and IL-1β. CXCL17 in the synovial fluid of RA was quantified by ELISA. A human umbilical vein endothelial cell culture assay was used to evaluate angiogenesis.
Results: CXCL17 is overexpressed in the synovial membrane of RA compared to OA (p=0.006) and detectable in the synovial fluid of RA (mean 310 pg/ml). INF-γ significantly induced CXCL17-mRNA and protein production in RA synovial fibroblasts (1.88-fold, p=0.019 and 2-fold, p=0.0002) and rat smooth muscle cells (67-fold, p=0.02 and 3.7-fold, p<0.001). In vitro angiogenesis was inhibited by CXCL17. Specific GPR35 antagonists reversed this effect.
Conclusion: CXCL17 is expressed in RA synovial tissue and detectable in synovial fluid of RA. Within the synovial membrane it localizes to vascular smooth muscle cells and fibroblasts and is inducible by INF-γ. CXCL17 inhibits angiogenesis, mediated by GPR35. CXCL17 and GPR35 may therefore constitute an unrecognized regulatory protein in RA pathogenesis.