Resistance to experimental colitis depends on cytoprotective heat shock proteins in macrophage migration inhibitory factor null mice.
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.
Ohkawara
Tatsuya
T
Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Kita15, Nishi7, Kita-ku, Sapporo 060-8638, Japan. tokawara@med.hokudai.ac.jp
Nishihira
Jun
J
Ishiguro
Yoh
Y
Otsubo
Eiji
E
Nagai
Koichi
K
Takeda
Hiroshi
H
Kato
Mototsugu
M
Yoshiki
Takashi
T
Iwanaga
Toshihiko
T
Asaka
Masahiro
M
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
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