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and IFN-
Regulate Expression and Function of the Fas System in the Seminiferous Epithelium
*
Department of Histology and Medical Embryology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome "La Sapienza," Rome, Italy;
Institute of Experimental Medicine, Consiglio Nazionale delle Ricerche, Rome, Italy; and
Department of Experimental Medicine, University of L’Aquila, Aquila, Italy
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-
and IFN-
markedly increase the
expression of both soluble and membrane-bound 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 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--stimulated Sertoli cell cultures inhibit
Neuro-2a FasL+-induced cell death. Taken together, our data
suggest a possible regulatory role of TNF- and IFN- on
Fas-mediated apoptosis in the testis through disruption of the balance
between different forms of Fas.
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