title: Opposite effects of interleukin-1alpha and transforming growth factor-beta2 induce stage-specific regulation of junctional adhesion molecule-B gene in Sertoli cells.
abstract: In the mammalian testis, junctional adhesion molecule-B (JAM-B) is found at the blood-testis barrier between Sertoli cells and the apical ectoplasmic specializations between Sertoli and germ cells. The expression of JAM-B is tightly regulated to allow the transit of developing germ cells across the blood-testis barrier and the timely release of mature spermatids at stage VIII. In this study, the basal transcription of JAM-B in the mouse Sertoli cell line, MSC-1 cells, was examined. We found that the constitutive expression of JAM-B is carried out by the binding of specificity proteins (Sps), ETS domain transcription factor Elk-1 (Elk1), neuron-restrictive silencer factor (NRSF), and E2F transcription factor 3 (E2F3) to various cis-acting elements including TG interacting factor (TGIF), Elk-1, NRSF, and proximal Sp1 (pSp1) + E2F binding motifs. We also investigated the effects of two cytokines IL-1alpha and TGF-beta2 on JAM-B expression. IL-1alpha promotes JAM-B expression by facilitating the binding of Elk-1 to TGIF and pSp1 + E2F motifs in a p38-dependent manner, which leads to an additive effect on Sp1- and NRSF-mediated JAM-B transactivation. TGF-beta2 inhibits JAM-B transcription via the activation of mothers against decapentaplegic (Smad) proteins and activated Smads compete with specificity proteins (Sp1 and Sp3) for the TGIF motif, resulting in JAM-B repression. IL-1alpha and Smad3 expression have been reported to be stage specific. IL-1alpha is absent in the seminferous epithelium at stages VII-VIII, whereas a high level of nuclear Smad3 level is found at the same stages. This study shows for the first time that IL-1alpha and TGF-beta2 regulate JAM-B expression in an opposite manner, and in vitro data obtained herein provide some clues on how junctions are regulated in the testis.
authors.affiliation: Division of Endocrinology, School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: Lui
mesh_terms: D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004336:Drug Antagonism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007136:Immunoglobulins / Q000235:genetics* / Q000378:metabolism; D053582:Interleukin-1alpha / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017422:Sequence Analysis, DNA; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology*; D062765:Junctional Adhesion Molecule B
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D053582:Interleukin-1alpha; D014157:Transcription Factors; D053781:Transforming Growth Factor beta2; C498781:Jam2 protein, mouse; D062765:Junctional Adhesion Molecule B; C509042:Tgfb2 protein, mouse