Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2005; 11(4): 573-576
Published online Jan 28, 2005. doi: 10.3748/wjg.v11.i4.573
Effect of 2-amino-2-[2-(4-octylphenyl) ethyl] propane-1,3-diol hydrochloride (FTY 720) on immune liver injury in mice
Jing-Hua He, Hui-Na Zhang, Zhi-Bin Lin
Jing-Hua He, Hui-Na Zhang, Zhi-Bin Lin, Department of Pharmacology, Basic Medical School, Peking University Health Science Center, Beijing 100083, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Zhin-Bin Lin, Department of Pharmacology, Basic Medical School, Peking University Health Science Center, Xueyuan Road, Haidian District, Beijing 100083, China. linzb@public3.bta.net.cn
Telephone: +86-10-62091686 Fax: +86-10-62091686
Received: November 13, 2003
Revised: November 14, 2003
Accepted: April 13, 2004
Published online: January 28, 2005
Abstract

AIM: To investigate the protective effect against two immune liver injury models in mice by 2-amino-2-[2-(4-octylphenyl) ethyl] propane-1,3-diol hydrochloride and its possible mechanisms in Con A-induced liver damage.

METHODS: Liver tissue or hepatocyte injury was monitored biochemically by measuring alanine aminotransferase (sALT) and aspartate aminotransferase (sAST) activity. Hematoxylin & eosin (HE) staining was used for histopathological examination. To evaluate the role of IFN-γ and IL-4 in the liver injury, serum levels of IFN-γ and IL-4 were determined using commercially available ELISA kit at 12 h after Con A challenge. We also determined FTY 720-induced spleen cell apoptosis by flow cytometry analysis or spleen cell proliferation test.

RESULTS: Different doses of FTY 720 treatment dramatically reduced circulating markers of hepatocyte injury in two kinds of immunological liver injury models. FTY 720 dramatically reduced the elevated serum IFN-γ and IL-4 levels after Con A injection. Effect of spleen cell supernatants treated with Con A or FTY 720 on hepatocytes showed that ALT activities in cultured hepatocyte supernatants in Con A treatment group increased markedly and FTY 720 could reduce this elevated ALT activities in FTY 720 treatment group. FTY 720 dose-dependently increased the percentage of apoptotic cells in T cells and inhibited splenocyte proliferation induced by Con A.

CONCLUSION: Pretreatment with FTY 720 was shown to produce protective effect on the immune liver injury in mice. The possible mechanism of FTY 720 on Con A-induced liver damage is that it could inhibit lymphocyte proliferation and induce lymphocyte apoptosis, resulting in the reduction of IL-4 or IFN-γ release, and subsequently protecting liver from being damaged by Con A.

Keywords: Immune liver injury; FTY 720; Apoptosis; Cell proliferation