title: Deficiency of Group VIA Phospholipase A2 (iPLA2β) Renders Susceptibility for Chemical-Induced Colitis.
abstract: BACKGROUND
  Inflammatory bowel disease results from a combination of dysfunction of intestinal epithelial barrier and dysregulation of mucosal immune system. iPLA2β has multiple homeostatic functions and shown to play a role in membrane remodeling, cell proliferation, monocyte chemotaxis, and apoptosis. The latter may render chronic inflammation and susceptibility for acute injury.
  
  
  OBJECTIVE
  We aim to evaluate whether an inactivation of iPLA2β would enhance the pathogenesis of experimental colitis induced by dextran sodium sulfate.
  
  
  METHODS
  iPLA2β-null male mice were administered dextran sodium sulfate in drinking water for 7 days followed by normal water for 3 days. At day 10, mice were killed, and harvested colon and ileum were subjected for evaluation by histology, immunohistochemistry, and quantitative RT-PCR.
  
  
  RESULTS
  Dextran sodium sulfate administration caused a significant increase in histological scores and cleaved caspase 3 (+) apoptosis concomitant with a decrease in colon length and crypt cell Ki67 (+) proliferation in iPLA2β-null mice in a greater extent than in control littermates. This sensitization by iPLA2β deficiency was associated with an increase in accumulation of F4/80 (+) macrophages, and expression of proinflammatory cytokines and chemokines, while the number of mucin-containing goblet cells and mucus layer thickness was decreased. Some of these abnormalities were also observed in the ileum.
  
  
  CONCLUSIONS
  An inactivation of iPLA2β exacerbated pathogenesis of experimental colitis by promoting intestinal epithelial cell apoptosis, inhibiting crypt cell regeneration, and causing damage to mucus barrier allowing an activation of innate immune response. Thus, iPLA2β may represent a susceptible gene for the development of inflammatory bowel disease.
authors.affiliation: Department of Toxicology, School of Public Health, Jilin University, Changchun, China.|Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany.
authors.forename: Li
authors.initials: L
authors.lastname: Jiao
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Inhoffen
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany.
authors.forename: Hongying
authors.initials: H
authors.lastname: Gan-Schreier
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Tuma-Kellner
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.affiliation: Department of Toxicology, School of Public Health, Jilin University, Changchun, China. zwsun@hotmail.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg Hospital, Heidelberg, Germany. Walee.Chamulitrat@med.uni-heidelberg.de.
authors.forename: Walee
authors.initials: W
authors.lastname: Chamulitrat
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003092:Colitis / Q000139:chemically induced*; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D054522:Group VI Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D016264:Dextran Sulfate; D054522:Group VI Phospholipases A2; C516476:Pla2g6 protein, mouse
keywords: Apoptosis; Colitis; Dextran sodium sulfate; Inflammatory bowel disease; Regeneration; iPLA2β