NF-kappaB induces cAMP-response element-binding protein gene transcription in sertoli cells.
Spermatogenesis is dependent upon Sertoli cells, which relay hormonal signals and provide factors required for the differentiation and proliferation of germ cells. NF-kappaB transcription factors are constitutively expressed in the nuclei of Sertoli cells in rodent testis. Electrophoretic mobility shift assays demonstrated that Sertoli NF-kappaB proteins specifically bind to kappaB enhancer motifs within the promoter of the cAMP-response element-binding protein (CREB) gene, an important mediator of hormonal signals that control spermatogenesis. Overexpression of NF-kappaB proteins in primary Sertoli and NIH 3T3 fibroblast cells induced the CREB promoter in transient transfection assays. Stimulation of Sertoli cells with tumor necrosis factor-alpha, an NF-kappaB-activating cytokine produced by round spermatids located adjacent to Sertoli cells, stimulated the elimination of IkappaB, the translocation of additional NF-kappaB to the nucleus, and increased NF-kappaB binding to CREB promoter kappaB enhancer elements. Tumor necrosis factor-alpha also stimulated transcription from the CREB promoter. These data demonstrate that NF-kappaB contributes to the up-regulation of CREB expression in Sertoli cells and raises the possibility that NF-kappaB may induce other Sertoli genes required for spermatogenesis. Furthermore, the CREB promoter is also inducible by NF-kappaB in NIH 3T3 cells suggesting that NF-kappaB may be a general regulator of CREB in non-testis tissues.
Delfino
F J
FJ
Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Walker
W H
WH
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney; D008156:Luciferases / Q000235:genetics; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases