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Adiponectin deficiency exacerbates lipopolysaccharide/ D-galactosamine-induced liver injury in mice

World Journal of Gastroenterology 2006年第21期12卷 3352-3358页

作者： Hitoshi Matsumoto shinji Tamura Yoshihiro Kamada Shinichi Kiso Juichi Fukushima Akira Wada Norikazu Maeda shinji kihara Tohru Funahashi Yuji Matsuzawa Iichiro Shimomura Norio Hayashi Department of Gastroenterology and Hepatology Osaka University Graduate School of Medicine2-2K1Yamada-okaSuitaOsaka 565-0871Japan Department of Metabolic Medicine Osaka University Graduate School of Medicine2-2B5Yamada-okaSuitaOsaka 565-0871Japan Sumitomo Hospital 5-3-20 Kita-Ku nakanoshimaOsaka530-0005Japan

AIM： To examine the effects of adiponectin on the functions of Kupffer cells, key modulators of lipopolysaccharide （LPS） -induced liver ***： D-galactosamine （GAIN） and LPS were injected intraperitoneally into adiponectin-/- mice and wild type mice. Kupffer cells, isolated from Sprague-Dawley rats, were preincubated with or without adiponectin, and then treated with ***： In knockout mice, GalN/LPS injection significantly lowered the survival rate, significantly raised the plasma levels of alanine transaminase and tumor necrosis factor-α （TNF-α） and significantly reduced IL-10 levels compared with wild type mice. TNF-α gene expression in the liver was which higher and those of IL-10 were lower in knockout mice than in wild type mice. In cultured adiponectin-pre-treated Kupffer cells, LPS significantly lowered TNF-α levels and raised IL-10 levels in the culture media and their respective gene expression levels, compared with Kupffer cells without ***： Adiponectin supresses TNF-α production and induces IL-10 production by Kupffer cells in response to LPS stimulation, and a lack of adiponectin enhances LPS-induced liver injury.

关键词： Adiponectin Lipopolysaccharide Kupffer cell TNF-alpha IL10

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Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice

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World Journal of Gastroenterology 2008年第42期14卷 6473-6480页

作者： Tamao Nishihara Miyako Baba Morihiro Matsuda Masahiro Inoue Yasuko Nishizawa Atsunori Fukuhara Hiroshi Araki shinji kihara Tohru Funahashi shinji Tamura Norio Hayashi Hiroyasu Iishi Iichiro Shimomura Department of Gastroenterology and Hepatology Graduate School of Medicine Osaka University 2-2 Yamada-oka Suita Osaka 565-0871 Japan Department of Pathology Osaka Medical Center for Cancer and Cardiovascular Diseases Research Institute 1-3-2 Nakamichi Higashinari-ku Osaka 537-8511 Japan Department of Metabolic Medicine Graduate School of Medicine Osaka University 2-2 Yamada-oka Suita Osaka 565-0871 Japan Department of Biochemistry Osaka MedicaCenter for Cancer and Cardiovascular Diseases ResearchInstitute 1-3-2 Nakamichi Higashinari-ku Osaka 537-8511Japan Department of Gastrointestinal Oncology Osaka Medical Center for Cancer and Cardiovascular Diseases 1-3-3 Nakamichi Higashinari-ku Osaka 537-8511 Japan

AIM:To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model,and to determine the con-tribution of adiponectin defi ciency to colorectal cancer development and ***:We examined the influence of adiponectin defi ciency on colorectal carcinogenesis induced by the administration of azoxymethane(AOM)(7.5 mg/kg,in-traperitoneal injection once a week for 8 wk),by using adiponectin-knockout(KO) ***:At 53 wk after the fi rst AOM treatment,KOmice developed larger and histologically more progres-sive colorectal tumors with greater frequency com-pared with wild-type(WT) mice,although the tumor incidence was not different between WT and KO *** mice showed increased cell proliferation of colorec-tal tumor cells,which correlated with the expression levels of cyclooxygenase-2(COX-2) in the colorectal *** addition,KO mice showed higher incidence and frequency of liver tumors after AOM *** percent of WT mice developed liver tumors,and these WT mice had only a single *** contrast,50% of KO mice developed liver tumors,and 58% of these KO mice had multiple ***:Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in *** study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.

关键词： Adiponectin Colorectal carcinogenesis Azoxymethane Cell proliferation Cyclooxygenase-2 Liver tumor formation

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