山梨医科学雑誌 第24巻2号 055-064(2009)

<Original>
Deficiency of Macrophage Colony-Stimulating Factor
Attenuates DSS-Induced Colitis in Mice

Kenichi ISHII, Hiroshi KONO1), Masahito OGIKU1), Naohiro HOSOMURA1),
Masato TSUCHIYA, Blair U BRADFORD, Ivan RUSYN, and Hideki FUJII

Abstract: The purpose of this study was to investigate the role of macrophage colony-stimulating factor (M-CSF)-induced macrophages (Mφs) in dextran sulfate sodium (DSS)-induced colitis. M-CSF deficient (op/op) mice and their control mice were administered with DSS in drinking water for 7 days, and then colonic specimens were harvested. Histopathological findings were evaluated, and distribution of Mφs in the colon was assessed. Moreover, protein concentration of inflammatory cytokines in the colon was determined. In another set of experiments, isolated Mφs from the colonic lamina propria were stimulated with lipopolysaccharide, and then cytokine production was measured. After treatment with DSS, control mice developed severe colitis, and the number of Mφs increased in the colon. In op/op mice, the number of Mφs was reduced, and colitis was inhibited. The protein concentrations of IFN-γ and IL-12 in the colon were increased in control mice but not in op/op mice after treatment with DSS. Furthermore, production of IL-12 by isolated Mφs was increased in control mice but not in op/op mice. Taken together, these results suggested that M-CSFinduced Mφs are most likely involved in the pathogenesis of inflammatory bowel diseases.

Key words: Macrophages, Osteopetroric mouse, Interferon gamma, Interleukin-12, Inflammatory bowel disease




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