TNF-a and IFN-g regulate expression and function of the fas system in 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 and Fas ligand (FasL) expression in the testis remains unknown. In the present study, we demonstrate that cultured mouse Sertoli cells constitutively express a low level of membrane-bound Fas protein, but not a soluble form of Fas. Sertoli cells stimulated with TNF-a and IFN-g markedly increase the expression of both soluble and membranebound Fas in a dose-dependent manner. The up-regulated membrane-bound Fas protein is functionally active because it induces a significant level of Sertoli cell death in the presence of Neuro-2a FasL1 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-astimulated Sertoli cell cultures inhibit Neuro-2a FasL1-induced cell death. Taken together, our data suggest a possible regulatory role of TNF-a and IFN-g on Fas-mediated apoptosis in the testis through disruption of the balance between different forms of Fas