Macrophage derived growth factors modulate Fas ligand expression in cultured endometrial stromal cells: a role in endometriosis

Fas-Fas ligand (Fast) interactions play a significant role in the immune privilege status of cel-tain cell populations, and several cytokines and growth factors can modulate their expression. When a Fast-expressing cell binds a Fas-bearing immune cell, it triggers its death by apoptosis. In this study, we demonstrate that normal human endometrial epithelial but not stromal cells express Fast. Moreover, we showed that macrophage-conditioned media induced Fast expression by endometrial stromal cells in a dose-dependent manner. To elucidate which macrophage product was responsible for the up-regulation of Fast, endometrial stromal cell cultures were treated with the macrophage products platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta(1) and basic fibroblast growth factor (bFGF). The first two (which are known to be elevated in the peritoneal; fluid of women with endometriosis) induced a dose-dependent upregulation of Fast expression, which was specifically inhibited by the antibody. Interestingly, bFGF (which is not elevated in peritoneal fluid of women with endometriosis) did not induce any response. These results suggest that the pro-inflammatory nature of the peritoneal fluid of women with endometriosis induces the Fast expression by regurgitated endometrial cells, and signals Fas-mediated cell death of activated immune cells. This could be a mechanism for endometrial cells to escape immune surveillance, implant and grow.