FAS ANTIGEN SIGNALS PROLIFERATION OF NORMAL HUMAN-DIPLOID FIBROBLAST AND ITS MECHANISM IS DIFFERENT FROM TUMOR-NECROSIS-FACTOR RECEPTOR

Recent cloning of the cDNA for Fas/Apo-1 and its ligand has revealed t hat they belong to the tumor necrosis factor (TNF) receptor and TNF fa mily, respectively, and play an important role in apoptosis (programme d cell death). Like TNF, antibodies against the Fas antigen (anti-Fas) have been shown to be cytotoxic to Fas-expressing cells. Whether Fas, like TNF receptor, also mediates proliferation of normal human diploi d fibroblasts (HDF), is not known. In this study, we show that HDF exp resses Fas antigen and the engagement of this antigen signals prolifer ation of these cells in a dose-dependent manner. Unlike TNF receptor, however, Fas-mediated proliferation of HDF could not be blocked by ort hovanadate, a tyrosine phosphatase inhibitor. The difference in the si gnaling was further evident from our observation that TNF induced the expression of interleukin-6 but anti-Fas did not. Overall, our results demonstrate for the first time that besides cell killing, Fas also me diates proliferation of HDF and that its mechanism is different from t hat of TNF receptor.