Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis.
Interleukin (IL-)17 is a T cell-derived pro-inflammatory cytokine produced by RA synovium. We studied the role of IL-17 in the synovium cytokine network to determine whether it can influence the inflammatory and destructive pattern characteristic of RA. Herein, we investigated whether the production and action of MMP-1 and its inhibitor TIMP-1 could be modulated by IL-17 in the presence of pro-inflammatory cytokine (IL-1) and anti-inflammatory cytokines (IL-4, IL-13, IL-10). The effect of the blockade of endogenous IL-17 on the secretion of MMP-1 and TIMP-1 by RA synovium and matrix destruction was also studied. IL-17 increased the spontaneous production of MMP-1 by synoviocytes five-fold. IL-1 was more potent since it increased MMP-1 production nine-fold. Addition of IL-4, IL-13 and IL-10 to synoviocyte cultures reduced the spontaneous production of MMP-1 and induced TIMP-1 production by synoviocytes stimulated with IL-17 or/and IL-1beta. In the presence of anti-IL-17 blocking mAb, MMP-1 production and collagenase activity by RA synovium was reduced by 50% and associated with a 50% reduction in type I collagen C-telopeptide fragments (CTX) released in the supernatants, demonstrating the direct contribution of IL-17 in destruction. IL-17 and its producing T cells appear to contribute to the inflammatory process involved in the rheumatoid lesion.
Chabaud
M
M
Department of Immunology and Rheumatology, Faculté de Médecine Laennec, Hôpital Edouard Herriot, Lyon, France.
Garnero
P
P
Dayer
J M
JM
Guerne
P A
PA
Fossiez
F
F
Miossec
P
P
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D020381:Interleukin-17 / Q000276:immunology*; D015847:Interleukin-4 / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
D018793:Interleukin-13; D020381:Interleukin-17; D019715:Tissue Inhibitor of Metalloproteinase-1; D016753:Interleukin-10; D015847:Interleukin-4; D017364:Collagenases; D020781:Matrix Metalloproteinase 1