INCREASED EXPRESSION OF INTERSTITIAL COLLAGENASE IN SILICA-TREATED FIBROBLASTS

Silica-associated scleroderma is a disease that does not differ from s ystemic sclerodema (SSc). Silica proved to be an inducer of fibrotic c hanges in the lung and in skin which may lead to the development of SS c. Besides the influence of silica on mononuclear blood cells investig ated previously, we found a direct influence of silica on dermal fibro blasts. Incubation of dermal fibroblasts with silica in non-toxic conc entrations increased the steady-state-level of mRNA for interstitial c ollagenase I in a dose-dependent manner. The expression of collagen ty pe I and III mRNAs was unaffected. In addition, the protein levels of these collagens also remained unchanged. Furthermore, we could demonst rate a decreased contractile force of silica-treated fibroblasts when seeded into three-dimensional collagen gels. These data support the id ea, that silica exerts a direct influence on fibroblasts, as shown by the synthesis rate of interstitial collagenase I and the functional ca pacity to contract collagen gels.