MODULATION OF INTERSTITIAL COLLAGENASE IN SCLERODERMA AND NORMAL FIBROBLASTS

Systemic sclerosis (SSc) is characterized by excessive deposition of c ollagen in the extracellular matrix (ECM). In vitro, SSc fibroblasts a re often distinguished from normal fibroblasts by an increased collage n production. A decreased collagenase activity supports the resulting accumulation of collagen in the ECM. However, in other studies unalter ed collagen and/or collagenase expression in SSc fibroblasts have been described, Currently, the participation of collagenase in the maintai nance of SSc is being debated. We have analysed the expression of coll agen type I and interstitial collagenase in fibroblasts derived from e leven SSc patients and three healthy people. Most of the SSc fibroblas ts cultures were characterized by increased collagen type I production at the mRNA and protein level. The interstitial collagenase expressio n was increased in eight SSc fibroblast cultures. SSc fibroblasts char acterized as collagen ''low producers'' show maximally elevated collag enase mRNA and protein levels. TGF-beta(1) treatment stimulated collag en type I production in ''low and high collagen producers'', but colla genase expression was down-regulated as expected only in ''high produc ers'' and up-regulated in ''low producers''. Therefore, we cannot impl icate TGF-beta alone as the only essential factor in the pathogenesis of SSc. A simultaneous incubation of fibroblasts with TGF-beta and TNF -alpha demonstrates that a concerted action of these cytokines is able to produce a quite different situation in SSc fibroblasts. Our result s suggest that SSc fibroblasts represent a heterogenous group, which i s characterized by a positive collagen net balance and not necessarily with increased collagen and decreased collagenase expression.