Loss of collagen type IV in rheumatoid synovia and cytokine effect on the collagen type-IV gene expression in fibroblast-like synoviocytes from rheumatoid arthritis

Collagen type IV is a structural matrix protein which contributes to the st ructural organization of the synovia. In order to characterize the distribu tion of this protein in synovia with chronic synovitis, collagen type IV wa s detected by immunochemistry in normal synovia and in synovia from patient s with osteoarthritis (OA) and rheumatoid arthritis (RA). A decrease of col lagen type IV was observed in synovial layers of rheumatoid synovia, which statistically correlated with the grade of inflammation and with the thickn ess of the synovial layer. In vitro, we found no differences in the gene ex pression of collagen type IV in cultures of fibroblast-like synoviocytes (F LS) derived from OA and RA using a reverse-transcriptase polymerase chain r eaction. Nevertheless, we observed a downregulating effect of tumor necrosi s factor-alpha and interleukin (IL)-1 beta on the gene expression of collag en type IV only in FLS isolated from patients with RA. The effect of IL-I b eta was dose dependent. In summary, we observed an inflammation-associated decrease of collagen type IV in the synovial layer of rheumatoid synovia. I nflammatory cytokines may play a role in regulating the synthesis of collag en type IV in the rheumatoid process in vivo.