Contribution of interleukin 17 to human cartilage degradation and synovial inflammation in osteoarthritis.
OBJECTIVE
To compare the effect of interleukin (IL)-17, IL-1beta and TNF-alpha on chemokine production by human chondrocytes and synovial fibroblasts isolated from patients with osteoarthritis (OA). The expression of IL-1beta mRNA by OA chondrocytes was also assessed, as well as the presence and expression of IL-17 receptor (IL-17R) in OA chondrocytes and synovial fibroblasts after stimulation with IL-17, IL-1beta and TNF-alpha.


METHODS
Synovial fibroblasts and chondrocytes isolated from patients with OA were stimulated in vitro with IL-17, IL-1beta or TNF-alpha. Supernatants were collected and immunoassayed for the presence of IL-8, GRO-alpha (CXC chemokines) and MCP-1, RANTES (CC chemokines). The cells were used to detect the presence of IL-17R and the expression of IL-17R mRNA. Stimulated chondrocytes were also used to detect IL-1beta production and mRNA expression.


RESULTS
IL-17 upregulated the release of IL-8 and GRO-alpha both by synovial fibroblasts and chondrocytes, and the release of MCP-1 only by chondrocytes. IL-17 was a weaker stimulator than IL-1beta and TNF-alpha, except for GRO-alpha release which was maximally upregulated by IL-1beta, less by IL-17 and minimally by TNF-alpha. When compared to IL-1beta, IL-17 was more active on chondrocytes than on fibroblasts. In chondrocytes the expression of IL-1beta mRNA was enhanced by IL-17 and TNF-alpha, with a maximum level reached by IL-1beta. IL-17 and TNF-alpha stimulated IL-1beta release in few subjects. Neither IL-17, IL-1beta nor TNF-alpha modulated the presence of IL-17R and the expression of IL-17R mRNA.


CONCLUSIONS
These data suggest that IL-17 could contribute to cartilage breakdown and synovial infiltration in OA by inducing both the release of chemokines by chondrocytes and synovial fibroblasts and, in a less extent, the synthesis of IL-1beta by chondrocytes.
D000328:Adult; D000368:Aged; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism / Q000494:pharmacology*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000187:drug effects* / Q000378:metabolism
D018925:Chemokines; D007375:Interleukin-1; D020381:Interleukin-17; D012333:RNA, Messenger