Basic Research
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World J Gastroenterol. Jun 7, 2006; 12(21): 3352-3358
Published online Jun 7, 2006. doi: 10.3748/wjg.v12.i21.3352
Adiponectin deficiency exacerbates lipopolysaccharide/D-galactosamine-induced liver injury in mice
Hitoshi Matsumoto, Shinji Tamura, Yoshihiro Kamada, Shinichi Kiso, Juichi Fukushima, Akira Wada, Norikazu Maeda, Shinji Kihara, Tohru Funahashi, Yuji Matsuzawa, Iichiro Shimomura, Norio Hayashi
Hitoshi Matsumoto, Shinji Tamura, Yoshihiro Kamada, Shinichi Kiso, Juichi Fukushima, Akira Wada, Norio Hayashi, Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2, K1, Yamada-oka, Suita, Osaka 565-0871, Japan
Norikazu Maeda, Shinji Kihara, Tohru Funahashi, Iichiro Shimomura, Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, 2-2, B5, Yamada-oka, Suita, Osaka 565-0871, Japan
Yuji Matsuzawa, Sumitomo Hospital, 5-3-20, Kita-Ku nakanoshima, Osaka, 530-0005, Japan
Correspondence to: Shinji Tamura, Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2, K1, Yamada-oka, Suita, Osaka 565-0871, Japan. tamura@gh.med.osaka-u.ac.jp
Telephone: +81-6-68793621 Fax: +81-6-68793629
Received: December 22, 2005
Revised: December 28, 2005
Accepted: January 24, 2006
Published online: June 7, 2006
Abstract

AIM: To examine the effects of adiponectin on the functions of Kupffer cells, key modulators of lipopolysaccharide (LPS) -induced liver injury.

METHODS: D-galactosamine (GalN) 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 LPS.

RESULTS: 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-pre-treatment.

CONCLUSION: 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.

Keywords: Adiponectin; Lipopolysaccharide; Kupffer cell; TNF-alpha; IL10