title: A chemical enterocolitis model in zebrafish larvae that is dependent on microbiota and responsive to pharmacological agents.
abstract: Inflammatory bowel disease (IBD) results from dysfunctional interactions between the intestinal immune system and microbiota, influenced by host genetic susceptibility. Because a key feature of the pathology is intestinal epithelial damage, potential disease factors have been traditionally analyzed within the background of chemical colitis models in mice. The zebrafish has greatly complemented the mouse for modeling aspects of disease processes, with an advantage for high content drug screens. Larval zebrafish exposed to the haptenizing agent trinitrobenzene sulfonic acid (TNBS) displayed impaired intestinal homeostasis and inflammation reminiscent of human IBD. There was a marked induction of pro-inflammatory cytokines, the degradative enzyme mmp9 and leukocytosis. Enterocolitis was dependent on microbiota and Toll-like receptor signaling, that can be ameliorated by antibiotic and anti-inflammatory drug treatments. This system will be useful to rapidly interrogate in vivo the biological significance of the IBD candidate genes so far identified and to carry out pharmacological modifier screens.
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Oehlers
authors.forename: Maria Vega
authors.initials: MV
authors.lastname: Flores
authors.forename: Kazuhide S
authors.initials: KS
authors.lastname: Okuda
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hall
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Crosier
authors.forename: Philip S
authors.initials: PS
authors.lastname: Crosier
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian; D004760:Enterocolitis / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control*; D041981:Gastrointestinal Tract / Q000098:blood supply / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology; D006241:Haptens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007814:Larva; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D054892:Metagenome / Q000502:physiology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid; D015027:Zebrafish / Q000196:embryology / Q000254:growth & development
chemical_list: D000893:Anti-Inflammatory Agents; D006241:Haptens; D053594:Myeloid Differentiation Factor 88; D014302:Trinitrobenzenesulfonic Acid