title: Macrophage migration inhibitory factor contributes to development of nonsteroidal anti-inflammatory drugs-induced gastric injury in mice.
abstract: Macrophage migration inhibitory factor (MIF) plays an important role in the development of inflammation. In this study, we evaluated the role of MIF in gastric injury induced by non-steroidal anti-inflammatory drugs (NSAIDs) in mice. To induce gastric injury, mice were intraperitnoneally injected with 35 mg/kg of indomethacin. The level of MIF protein was up-regulated and severe gastric injury with inflammatory infiltrate was observed in the stomach of wild-type (WT) mice treated with indomethacin. The severity of gastric injury in MIF-deficient mice was less than that in WT mice. Increase in TNF-α in gastric tissue of mice treated with indomethacin was suppressed in MIF-deficient mice. The expression of HSP70, which has a cytoprotective role, was remarkably up-regulated in the stomach of MIF-deficient mice compared with WT mice after indomethacin treatment. Our results suggest that MIF is essential for the development of gastric injury-induced by NSAIDs.
authors.affiliation: Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Sapporo 060-8638, Japan. tatsuya-ohkawara@umin.ac.jp
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohkawara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Kato
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007213:Indomethacin / Q000009:adverse effects*; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis* / Q000502:physiology*; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis* / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse; D007213:Indomethacin