Fas antigen (CD95) mediates cell survival signals to regulate functional cellular subpopulations in normal human...

Fas antigen (CD95) is expressed on almost all types of human cells and is believed to mediate receptor-specific apoptotic signals. In human endometrial tissues, high Fas and Fas ligand expressions and Fas-mediated apoptosis in endometrial epithelial cells have been discussed in many reports but no study has examined Fas-mediated signals in endometrial stromal cells. In this study we investigated Fas expression and Fas-mediated signals of normal human endometrial stromal cells. Flow cytometric analysis revealed Fas antigen expression on the stromal cells and their Fas expression was enhanced by 8-Br-cAMP, a strong inducer of decidualization. Neither short-term nor long-term cultures with anti-Fas IgM affected proliferation or viability of the stromal cells. Anti-Fas IgM alone affected neither viable cell numbers nor PRL release of unstimulated stromal cells. However, anti-Fas IgM dose-dependently stimulated viable cell numbers of stromal cells co-stimulated with 8-Br-cAMP and anti-Fas IgM, whereas PRL secretion of the co-stimulated cells was not affected. Anti-Fas IgM dose-dependently stimulated viable cell numbers of 8-Br-cAMP-stimulated cells but did not affect PRL secretion of 8-Br-cAMP-induced decidualized cells. These results indicate that Fas antigen on human endometrial stromal cells cannot mediate receptor-specific apoptotic signals, and that Fas-mediated signals stimulate survival of 8-Br-cAMP-stimulated non-decidualized stromal cells. Thus, stimulation of Fas-antigen on the endometrial stromal cells enhances anti-apoptotic/survival signals in certain stromal cells, autoregulating functional cellular subpopulations of human endometrial stromal cells in a paracrine manner.