TNF-alpha and IFN-gamma regulate expression and function of the Fas systemin the seminiferous epithelium

Sertoli cells have long been considered to be involved in the regulation of the immune response in the testis, More recently, the Fas system has been implicated in the maintenance of the immune privilege in the testis as well as in the regulation of germ cell apoptosis, However, the control of Fas a nd Fas ligand (FasL) expression in the testis remains unknown. In the prese nt study, we demonstrate that cultured mouse Sertoli cells constitutively e xpress a low level of membrane-bound Fas protein, but not a soluble form of Fas, Sertoli cells stimulated with TNF-alpha and IFN-gamma markedly increa se the expression of both soluble and membrane-bound Fas in a dose-dependen t manner. The up-regulated membrane-bound Fas protein is functionally activ e because it induces a significant level of Sertoli cell death in the prese nce of Neuro-2a FasL(+) effector cells. Interestingly, the soluble form of Fas, which is induced by the same cytokines but has an antiapoptotic effect , is also functional. In fact, conditioned media from TNF-alpha-stimulated Sertoli cell cultures inhibit Neuro-2a FasL(+)-induced cell death. Taken to gether, our data suggest a possible regulatory role of TNF-alpha and IFN-ga mma on Fas-mediated apoptosis in the testis through disruption of the balan ce between different forms of Fas.