肝损伤
刀豆蛋白A
体内
环氧合酶
药理学
前列腺素E
前列腺素
免疫系统
炎症
前列腺素E2
发病机制
医学
免疫学
体外
化学
内科学
生物
酶
生物化学
生物技术
作者
Hao Yin,Linling Cheng,Robert Langenbach,Cynthia Ju
出处
期刊:Hepatology
[Lippincott Williams & Wilkins]
日期:2006-12-22
卷期号:45 (1): 159-169
被引量:50
摘要
Studies of the molecular and cellular mechanisms of concanavalin A (ConA)-induced liver injury have provided important knowledge on the pathogenesis of many liver diseases involving hepatic inflammation. However, studies identifying hepato-protective factors based on the mechanistic understanding of this model are lacking. Evidence suggests that certain prostaglandin (PG) products of cyclooxygenase (COX)-1 and COX-2 provide important anti-inflammatory and cytoprotective functions in some pathophysiological states. In the present study, we demonstrate a protective role of COX-2 derived PGs in ConA-induced liver injury. COX-2−/− mice developed much more severe liver damage upon ConA treatment compared with wild-type and COX-1−/− mice. Treatment of COX-2−/− mice with misoprostol (a PGE1/2 analog) or beraprost (a PGI2 analog) significantly decreased ConA-induced liver injury. Data from both in vivo and in vitro experiments demonstrated that misoprostol and beraprost acted directly on hepatic leukocytes, including natural killer (NK)T and T cells, and down-regulated their production of interferon (IFN)-γ, which are critical in mediating ConA-induced tissue damage. Collectively, the results provide strong evidence that the protective effects of COX-2 within the liver are mediated through the production of PGE2 and PGI2, which exert anti-inflammatory functions. These findings suggest that COX-2-derived PGs may have great therapeutic potentials in treating patients with inflammatory liver diseases. (Hepatology 2007;45:159–169.)
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