title: Interleukin-1β Mediates β-Catenin-Driven Downregulation of Claudin-3 and Barrier Dysfunction in Caco2 Cells.
abstract: IL-1β is a cytokine involved in mediating epithelial barrier dysfunction in the gut. It is known that IL-1β mediates activation of non-muscle myosin light chain kinase in epithelial cells, but the precise mechanism by which epithelial barrier dysfunction is induced by IL-1β is not understood.
  
  
  
  Using a Caco2 cell model, we show that the expression of the tight junction protein, claudin-3, is transcriptionally downregulated by IL-1β treatment. In addition, after assessing protein and mRNA expression, and protein localization, we show that inhibition of nmMLCK rescues IL-1β-mediated decrease in claudin-3 expression as well as junction protein redistribution. Using chromatin immunoprecipitation assays, we also show that β-catenin targeting of the claudin-3 promoter occurs as a consequence of IL-1β-mediated epithelial barrier dysfunction, and inhibition of nmMLCK interferes with this interaction.
  
  
  
  Taken together, these data represent the first line of evidence demonstrating nmMLCK regulation of claudin-3 expression in response to IL-1β-treated epithelial cells.
authors.affiliation: Department of Surgery, University of South Florida, Morsani College of Medicine, 12901 Bruce B. Downs Blvd., MDC 8, Office MDC 2012, Tampa, FL, 33612, USA.|James A. Haley Veterans' Hospital, Tampa, FL, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Haines
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida, Morsani College of Medicine, Tampa, FL, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Beard
authors.affiliation: Department of Surgery, University of South Florida, Morsani College of Medicine, 12901 Bruce B. Downs Blvd., MDC 8, Office MDC 2012, Tampa, FL, 33612, USA.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Surgery, University of South Florida, Morsani College of Medicine, 12901 Bruce B. Downs Blvd., MDC 8, Office MDC 2012, Tampa, FL, 33612, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Eitnier
authors.affiliation: Department of Surgery, University of South Florida, Morsani College of Medicine, 12901 Bruce B. Downs Blvd., MDC 8, Office MDC 2012, Tampa, FL, 33612, USA. mwu1@health.usf.edu.|James A. Haley Veterans' Hospital, Tampa, FL, USA. mwu1@health.usf.edu.
authors.forename: M H
authors.initials: MH
authors.lastname: Wu
mesh_terms: D001381:Azepines / Q000494:pharmacology; D018938:Caco-2 Cells; D047369:Chromatin Immunoprecipitation; D062465:Claudin-3 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D051176:beta Catenin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D001381:Azepines; C568122:CLDN3 protein, human; D062465:Claudin-3; D004791:Enzyme Inhibitors; C508585:IL1B protein, human; D053583:Interleukin-1beta; D009281:Naphthalenes; D012333:RNA, Messenger; D051176:beta Catenin; C070571:ML 7; D009219:Myosin-Light-Chain Kinase; C000593292:non-muscle myosin light-chain kinase, human
keywords: Claudin-3; Epithelial barrier; Interleukin-1β; Non-muscle myosin light chain kinase; Permeability; β Catenin