title: Induction of matrix metalloproteinases and TLR2 and 6 in murine colon after oral exposure to Mycobacterium avium subsp. paratuberculosis.
abstract: Mycobacterium avium subspecies paratuberculosis (MAP) is suspected to be a causative agent in Crohn's disease. Recent evidence suggests that MAP can induce the expression of Matrix Metalloproteinases (MMPs), which are the main proteases in the pathogenesis of mucosal ulcerations in inflammatory bowel disease (IBD). Within the present study, we analysed whether oral MAP exposure can induce colonic MMP expression in vivo. In MAP exposed mice MAP and spheroplasts were visualized in intramucosal leukocyte aggregates. MAP exposed mice exhibited a higher colonic expression of Mmp-2, -9, -13, -14, Timp-1, Tlr2, Tlr6, Il-1β, and Tnf-α. Cell clusters of MMP-9 positive cells adjacent to intramucosal leukocyte aggregates and CD45(+) leukocytes were identified as the major cellular sources of MMP-9. Enhanced TLR2 expression was visualized on the luminal side of colonic enterocytes. Although MAP exposure did not lead to macroscopic intestinal inflammation, the observed MAP spheroplasts in intramucosal leukocyte aggregates together with increased colonic expression of toll-like receptors, pro-inflammatory cytokines, and MMPs upon MAP exposure represents a part of the host immune response towards MAP.
authors.affiliation: Department of Gastroenterology, Medical Clinic II, Justus-Liebig-University, Klinikstrasse 33, D-35385 Giessen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Roderfeld
authors.forename: Arzu
authors.initials: A
authors.lastname: Koc
authors.forename: Timo
authors.initials: T
authors.lastname: Rath
authors.forename: Sonja
authors.initials: S
authors.lastname: Blöcher
authors.forename: Annette
authors.initials: A
authors.lastname: Tschuschner
authors.forename: Ömer
authors.initials: Ö
authors.lastname: Akineden
authors.forename: Marta
authors.initials: M
authors.lastname: Fischer
authors.forename: Susanne
authors.initials: S
authors.lastname: von Gerlach
authors.forename: Ralph
authors.initials: R
authors.lastname: Goethe
authors.forename: Elke
authors.initials: E
authors.lastname: Eckelt
authors.forename: Jochen
authors.initials: J
authors.lastname: Meens
authors.forename: Michael
authors.initials: M
authors.lastname: Bülte
authors.forename: Tina
authors.initials: T
authors.lastname: Basler
authors.forename: Elke
authors.initials: E
authors.lastname: Roeb
mesh_terms: D000818:Animals; D003106:Colon / Q000382:microbiology*; D003424:Crohn Disease / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D005786:Gene Expression Regulation; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016927:Mycobacterium avium subsp. paratuberculosis / Q000472:pathogenicity*; D010283:Paratuberculosis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000235:genetics / Q000378:metabolism*
chemical_list: C493486:Tlr2 protein, mouse; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D020782:Matrix Metalloproteinases