MATRIX METALLOPROTEINASES, IL-6, AND NITRIC-OXIDE IN RAT ANTIGEN-INDUCED ARTHRITIS

Objective Degradation of extracellular matrix by matrix metalloprotein ases (MMPs) is believed to be important in processes leading to the pr ogressive destruction of joints in rheumatoid arthritis (RA). We used the model of antigen-induced arthritis (AIA) to study MMP activity and the influence of cytokines on their expression by synoviocytes. Mater ial and methods Procedures used were: mBSA-induced arthritis in rats; investigation of synovial fluids and supernatants of cultured synovioc ytes at different time paints during AIA; estimation of total MMP acti vities by fluorescence assay; zymographic investigations; IL-6 bioassa y with B9 cells; nitric oxide (NO) estimation. Results Total MMP activ ity in the synovial fluids of arthritic joints was higher than in the contralateral joints or in the joints of untreated control animals. Th e maximum was noted between day 7 and day 14 after arthritis induction . Cultured synoviocytes, prepared at different time points after arthr itis induction, secreted MMPs into the media with a maximum time lapse of 14 days after arthritis induction. TNF-alpha increased the total M MP activity released. Moreover, TNF-alpha as well as IL-1 beta induced the expression of MMP9. Finally, TNF-alpha increased the levels of IL -6 and NO in the supernatants of synoviocytes; the extent of stimulati on was dependent on the course of AIA. Conclusions Different MMPs are synthesized in varying concentrations during the course of rat AIA. Cy tokines such as TNF-alpha and IL-1 beta differentially influence the a ctivity and expression of MMPs in cultured synoviocytes. The participa tion of MMPs in tissue degradation during the course of arthritis may be of importance for the development of new therapeutic strategies.