TNFα Down-Regulates the Fas Ligand and Inhibits Germ Cell Apoptosis in the Human Testis
- 1 September 2001
- journal article
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 86 (9), 4480-4488
- https://doi.org/10.1210/jcem.86.9.7861
Abstract
The cytokine TNFalpha is known to be secreted by testicular germ cells. However, its effect on maturing germ cells is unknown, and its role in the regulation of spermatogenesis is unclear. Here we aimed at characterizing the effects of TNFalpha on germ cell survival in the human testis. We found that TNFalpha effectively and dose-dependently inhibited germ cell apoptosis, which was induced in vitro by incubating segments of human seminiferous tubules under serum-free culture conditions. EMSAs indicated increased activity of nuclear factor kappaB in seminiferous tubules cultured under apoptosis-inducing conditions. However, we did not observe any significant effect of TNFalpha on the activation of this transcription factor, which is often considered to be a mediator of TNFalpha-induced survival signals. As the expression of the TNF receptor protein in the human seminiferous epithelium was predominantly found in the Sertoli cells, the antiapoptotic effect of TNFalpha is probably mediated via these somatic cells. Interestingly, expression of the Fas ligand, a known inductor of testicular apoptosis, was down-regulated by TNFalpha. Thus, in the seminiferous tubules, germ cell-derived TNFalpha may regulate the level of the Fas ligand and thereby control physiological germ cell apoptosis.Keywords
This publication has 31 references indexed in Scilit:
- NF-κB Induces cAMP-response Element-binding Protein Gene Transcription in Sertoli CellsPublished by Elsevier BV ,1999
- Control of apoptosis by Rel/NF-κB transcription factorsOncogene, 1999
- Activation of Jun N-terminal Kinase/Stress-activated Protein Kinase Pathway by Tumor Necrosis Factor α Leads to Intercellular Adhesion Molecule-1 ExpressionJournal of Biological Chemistry, 1999
- In vitro regulation of rat Sertoli cell transferrin expression by tumor necrosis factor α and retinoic acidMolecular and Cellular Endocrinology, 1999
- Mechanism for Biphasic Rel A· NF-κB1 Nuclear Translocation in Tumor Necrosis Factor α-stimulated HepatocytesPublished by Elsevier BV ,1997
- Clinical aspects of male germ cell apoptosis during testis development and spermatogenesisCell Death & Differentiation, 1997
- Apoptosis by Death FactorCell, 1997
- Tumor Necrosis Factor α Receptor p55 Is under Hormonal (Follicle-Stimulating Hormone) Control in Testicular Sertoli CellsBiochemical and Biophysical Research Communications, 1996
- A role for CD95 ligand in preventing graft rejectionNature, 1995
- Tumor necrosis factor Characterization at the molecular, cellular and in vivo levelFEBS Letters, 1991