Inhibition of microglial fatty acid amide hydrolase modulates LPS stimulated release of inflammatory mediators

被引：42

作者：

Tham, Chui-Se

Whitaker, John

Luo, Lin

Webb, Michael

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, San Diego, CA 92121 USA

[2] Southmead Gen Hosp, Westbury Trym, Bristol BS10 5NB, Avon, England

来源：

FEBS LETTERS | 2007年 / 581卷 / 16期

关键词：

FAAH; fatty acid amide hydrolase; fatty acid amide; endocannabinoid; microglia; cannabinoid receptor; iNOS; nitric oxide; cyclo-oxygenase; 2; prostaglandin E2; TNF; URB597;

D O I：

10.1016/j.febslet.2007.05.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Anandamide and other fatty acid amides are metabolised by the enzyme fatty acid amide hydrolase (FAAH), which thereby regulates their endogenous levels. Here we demonstrate that cultured rat cortical microglia express FAAH at low levels. The potent FAAH inhibitor URB597 reduced the LPS stimulated microglial expression of cyclo-oxygenase 2 and inducible nitric oxide, with concomitant attenuation of the release of PGE2 and NO. Additional of supplemental exogenous anandamide did not increase the magnitude of attenuation of mediator release. The effect of URB597 on LPS stimulated PGE2 release was not blocked by selective CB1 or CB2 receptor antagonists. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：2899 / 2904

页数：6

共 21 条

[1] Exceptionally potent inhibitors of fatty acid amide hydrolase: The enzyme responsible for degradation of endogenous oleamide and anandamide [J].