SILICA DIRECTLY INDUCES INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) EXPRESSION IN CULTURED ENDOTHELIAL-CELLS

Silica-induced scleroderma is a disease that does not differ from syst emic scleroderma (SSc). Silica has proved to trigger fibrotic changes in the lung and in the skin. Silica acts in two ways: firstly, it may modulate the function of-endothelial cells (EC) and dermal fibroblasts indirectly via immunological mechanisms by the release of inflammator y cytokines from monocytes; secondly, it could also directly alter the regulation of protein expression in these cells. The aim of the prese nt study was to show a possible response of EC towards the direct acti on of silica. Endothelial cells from different sources were used: huma n dermal microvascular endothelial cells (HDMEC) and human umbilical v ein endothelial cells (HUVEC), The expression of ICAM-1, interleukin-1 beta, IL-6 and interstitial collagenase I was studied at transcriptio nal and post-translational levels by Northern-blot analysis, FACS-anal ysis and ELISA. Incubation of EC with silica in non-toxic concentratio ns increased the steady-state levels of the mRNA for ICAM-1 and the co rresponding levels of this cell surface-protein and soluble protein in a dose- and time-dependent manner. Additionally, we found significant ly increased levels of interleukin-6 in the culture supernatants of EC . On the other hand, we found a significant increase of collagenase I mRNA in HDMEC. In conclusion, silica seems to be a potent activator of EC in vitro.