title: Interleukin 1alpha-induced disruption of the Sertoli cell cytoskeleton affects gap junctional communication.
abstract: Gap junctions (GJ) are transmembrane channels that connect the cytoplasms of adjacent cells, thereby facilitating the rapid exchange of ions, second messengers, and metabolites smaller than 1kDa. Connexin 43, the best-studied GJ protein, is a component of the Sertoli cell barrier/blood-testis barrier (BTB). To gain insight into the biology of the BTB, we investigated the effects of interleukin 1alpha (IL1A), a pro-inflammatory cytokine that disrupts BTB function, on gap junctional communication (GJC) in Sertoli cells. Compared with controls, the levels of connexin 43 and connexin 43 (Ser 368) increased ~30- and 20-fold, respectively, at 24 h after IL1A treatment. To assess GJ function, we investigated fluorescence recovery in photobleached Sertoli cells after vehicle or IL1A treatment. Compared with the control, IL1A affected the ability of calcein to return to photobleached cells, indicating that GJC was compromised. To explain the effects of IL1A on GJ function, the involvement of the Sertoli cell cytoskeleton was investigated. Stress fibers aggregated at the periphery of Sertoli cells treated with IL1A. These results were substantiated by a biochemical assay that showed IL1A to disrupt the bundling of exogenous F-actin by Sertoli cells. In summary, IL1A regulates GJC in Sertoli cells, which is critical for BTB restructuring.
authors.affiliation: Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY, USA.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Chojnacka
authors.affiliation: Department of Endocrinology, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bilinska
authors.affiliation: Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY, USA. Electronic address: mruk@popcbr.rockefeller.edu.
authors.forename: Dolores D
authors.initials: DD
authors.lastname: Mruk
mesh_terms: D000818:Animals; D001814:Blood-Testis Barrier / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D053582:Interleukin-1alpha / Q000494:pharmacology*; D008297:Male; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D022502:Stress Fibers / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D002227:Carbazoles; D018031:Connexin 43; D053582:Interleukin-1alpha; D047428:Protein Kinase Inhibitors; C081021:Go 6976; D051571:Protein Kinase C-alpha
keywords: Cytoskeleton; Gap junction; Interleukin 1alpha; Sertoli cell; Testis