SYNOVIOCYTES IN CHRONIC SYNOVITIS IN-SITU AND CYTOKINE-STIMULATED SYNOVIAL-CELLS IN-VITRO NEO-EXPRESS ALPHA-1, ALPHA-3 AND ALPHA-5 CHAINS OF BETA-1 INTEGRINS

The expression of the beta 1 integrins was examined immunohistochemica lly in synoviocytes from normal synovial membrane and from chronic syn ovitis of different aetiology and intensity. Normal synoviocytes were alpha 6 beta 1-positive but lacked al through alpha 5. In mild inflamm ation type A synoviocytes neo-expressed alpha 1, alpha 3, and alpha 5 chains. In severe inflammation both type A and B synoviocytes expresse d alpha 3, alpha 4, alpha 5, and alpha 6 chains. The effects of inflam matory cytokines, as single agents or in combination, on the beta 1 in tegrin expression in cultured normal synoviocytes was determined by im munocytochemistry and flow cytometry. The alpha 1 chain, while absent in unstimulated synoviocytes, was induced by interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). This effect was enhanced by combining IL-1 beta and TNF-a lpha. Expression of the alpha 3 chain was up-regulated by IL-1 beta an d, more intensely, by IFN-gamma. Transforming growth factor beta (TGF- beta) inhibited the up-regulating effect of IL-1 beta and antagonized the effect of IFN-gamma on alpha 3 chain expression. Expression of the alpha 5 chain was up-regulated significantly by co-stimulation throug h IL-1 beta together with TGF-beta or TNF-alpha. Thus, the beta 1 inte grin profile of cytokine activated synoviocytes in vitro resembled tha t of synoviocytes in synovitis in situ. These data suggest that IL-1 b eta, TNF-alpha, IFN-gamma, and TGF-beta are likely to be among the eff ecters regulating beta 1 integrin expression in synoviocytes in vivo.