title: Resistance to experimental colitis depends on cytoprotective heat shock proteins in macrophage migration inhibitory factor null mice.
abstract: Macrophage migration inhibitory factor plays an important role in inflammatory diseases. We investigated the role of macrophage migration inhibitory factor (MIF) in the development of dextran sulfate sodium (DSS)-induced colitis using MIF null ((-/-)) mice. MIF(-/-) mice given 3% DSS showed no clinical and histological feature of colitis in contrast to wild-type (WT) mice. Lack of MIF suppressed the up-regulation of TNF-alpha and IFN-gamma as Th1-derived cytokines, and increased the level of IL-4 as Th2-derived cytokine in the colon tissues. Moreover, we found that the expressions of heat shock protein (HSP)40 and HSP70 were markedly up-regulated in the colon of MIF(-/-) mice in response to DSS compared with WT mice. Additionally, quercetin, an inhibitor of HSP synthesis, inhibited the up-regulation of HSP40 and 70 expressions and developed DSS-induced colitis in MIF(-/-) mice. Our findings in this study provide more information in the role of MIF in colitis.
authors.affiliation: Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Kita15, Nishi7, Kita-ku, Sapporo 060-8638, Japan. tokawara@med.hokudai.ac.jp
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohkawara
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.forename: Yoh
authors.initials: Y
authors.lastname: Ishiguro
authors.forename: Eiji
authors.initials: E
authors.lastname: Otsubo
authors.forename: Koichi
authors.initials: K
authors.lastname: Nagai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Kato
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshiki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asaka
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D050956:HSP40 Heat-Shock Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D011794:Quercetin / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016264:Dextran Sulfate; D011794:Quercetin