title: Murine colitis is mediated by vimentin.
abstract: Vimentin, an abundant intermediate filament protein, presumably has an important role in stabilizing intracellular architecture, but its function is otherwise poorly understood. In a vimentin knockout (Vim KO) mouse model, we note that Vim KO mice challenged with intraperitoneal Escherichia coli control bacterial infection better than do wild-type (WT) mice. In vitro, Vim KO phagocytes show significantly increased capacity to mediate bacterial killing by abundant production of reactive oxygen species (ROS) and nitric oxides, likely due to interactions with the p47phox active subunit of NADPH oxidase. In acute colitis induced by dextran sodium sulfate (DSS), Vim KO mice develop significantly less gut inflammation than do WT mice. Further, Vim KO mice have markedly decreased bacterial extravasation in the setting of DSS-induced acute colitis, consistent with decreased intestinal disease. Our results suggest that vimentin impedes bacterial killing and production of ROS, thereby contributing to the pathogenesis of acute colitis.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI 48109-5640, USA. morkvak@umich.edu
authors.forename: Nirit
authors.initials: N
authors.lastname: Mor-Vaknin
authors.forename: Maureen
authors.initials: M
authors.lastname: Legendre
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.forename: Carlos H C
authors.initials: CH
authors.lastname: Serezani
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Garg
authors.forename: Anna
authors.initials: A
authors.lastname: Jatzek
authors.forename: Michael D
authors.initials: MD
authors.lastname: Swanson
authors.forename: Marta J
authors.initials: MJ
authors.lastname: Gonzalez-Hernandez
authors.forename: Seagal
authors.initials: S
authors.lastname: Teitz-Tennenbaum
authors.forename: Antonello
authors.initials: A
authors.lastname: Punturieri
authors.forename: N Cary
authors.initials: NC
authors.lastname: Engleberg
authors.forename: Ruma
authors.initials: R
authors.lastname: Banerjee
authors.forename: Marc
authors.initials: M
authors.lastname: Peters-Golden
authors.forename: John Y
authors.initials: JY
authors.lastname: Kao
authors.forename: David M
authors.initials: DM
authors.lastname: Markovitz
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004926:Escherichia coli / Q000472:pathogenicity; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D014746:Vimentin; D009569:Nitric Oxide; D016264:Dextran Sulfate; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1