Einfluss von Interleukin 17 auf chondrogene Vorläuferzellen in der rheumatoiden Arthritis

Abstract

Rheumatoid Arthritis is a chronic inflammatory joint disease of still unknown etiology leading to progressive joint destruction. Immunoregulatory cells, synoviocytes and cartilage cells were previously shown to play an important pathogenic role in rheumatoid arthritis. Further it was shown that the amount of the proinflammatory cytokine Interleukin 17 (IL17) is increased in synovial fluid of patient with rheumatoid arthritis. Therefore it is suggested that IL17 is playing an important role in the pathology of rheumatoid arthritis. Recently, a novel chondrogenic progenitor cell population were isolated from cartilage tissue of patient with rheumatoid arthritis.. It was shown that chondrogenic progenitor cell populations are expressing an IL17 receptor complex on its surface. Therefore we suggest to see an effect of IL17 stimulation on this specialized cell population . Method: Chondrogenic progenitor cells could be generated from human cartilage tissue of patient with rheumatoid arthritis. The cells were incubated with IL17 and further analysis were demonstrated by cell culter analysis, real-time PCR, fluorescence microscopy and western blot. Results: We could show an effect of IL17 stimulation on cell growth of chondrogenic progenitor cells in the first days of cell culture. The gene expression of chondrogenic progenitor cells revealed the following mRNA-molecules: IL6, IL1, MMPs (MMP3, MMP14,MMP15, MMP17) and following: NFkB, , MAPK1, IL1, Aggrecan, ADAMTS-5 and TIMP3. After IL17 stimulation we could show increased expression of MMP3, IL6, MMP17 and NFKb in chondrogenic progenitor cells, whereas there was no significant change in expression of MMP14, MMP15. We could demonstrate the expression of IL6 and MMP3 within the chondrogenic progenitor cells on protein level due to western blot and fluorescence microscopy. An interleukin 17 antibody was capeable of blocking the previously shown effects of IL17 stimulation on IL 6 expression in chondrogenic progenitor cells. Conclusion:IL17 seems to play an important role in the pathology of rheumatoid arthritis. Chondrogenic progenitor cells happen to have a certain reaction pattern on IL17 stimulation, which seems to results in further progression of rheumatoid arthritis. Blocking this shown IL17 effects in rheumatoid arthritis could be one further target in the rheumatoid arthritis therapy. But that has to be proofed in further studies.