10t, 12c-conjugated linoleic acid inhibits lipopolysaccharide-induced cyclooxygenase expression in vitro and in vivo
10t, 12c-conjugated linoleic acid inhibits lipopolysaccharide-induced cyclooxygenase expression in vitro and in vivo
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DOI：
10.1194/jlr.m500064-jlr200
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发表时间：
2005-10-01
影响因子：
6.5
通讯作者：
Cook, ME
中科院分区：
文献类型：
--
作者：
Li, GM;Barnes, D;Cook, ME
以前的数据表明，共轭亚油酸(CLA)减少了选定器官中二十烷类化合物的释放。我们假设，一个活性的CLA异构体是前列腺素释放减少的原因，其机制是通过抑制诱导性环氧合酶2(COX-2)。在此，我们研究了10t，12c-CLA和9c，11t-CLA对COX-2蛋白/mRNA表达和前列腺素E2(PGE2)产生的影响，以及CLA影响COX-2表达和前列腺素释放的机制。10t，12c-CLA和9c，11t-CLA分别抑制COX-2蛋白表达的80%和26%。10t，12c-CLA组小鼠肺组织COX-2蛋白表达减少34%，PGE2释放减少43%，9c，11t-CLA组小鼠肺组织中PGE2的释放量减少43%。10T，12c-CLA在体外100mU M时可使COX-2mRNA表达水平降低30%，体内可使小鼠肺组织COX-2mRNA表达水平降低30%。COX-2mRNA的降低与10t，12c-CLA抑制核因子-kappaB(NF-kappa B)途径有关。提示10t，12c-CLA抑制NF-kappaB可能是其降低COX-2表达和PGE2释放的机制之一。
Previous data demonstrated that conjugated linoleic acid ( CLA) reduced eicosanoid release from select organs. We hypothesized that one active CLA isomer was responsible for the reduced prostaglandin release and that the mechanism was through the inhibition of inducible cyclooxygenase2 ( COX- 2). Here, we examined the effects of 10t, 12c- CLA and 9c, 11t- CLA on COX- 2 protein/ mRNA expression, prostaglandin E 2 ( PGE 2) production, and the mechanism by which CLA affects COX- 2 expression and prostaglandin release. The COX- 2 protein expression level was inhibited 80% by 10t, 12c- CLA and 26% by 9c, 11t- CLA at 100 mu M in vitro. PGE 2 production was decreased from 5.39 to 1.12 ng/ 2 x 10(6) cells by 10t, 12c- CLA and from 5.7 to 4.5 ng/ 2 x 10(6) cells by 9c, 11t-CLA at 100 mu M. Mice fed 10t, 12c- CLA but not 9c, 11t- CLA were found to have a 34% decrease in COX- 2 protein and a 43% reduction of PGE 2 release in the lung. 10t, 12c- CLA reduced COX- 2 mRNA expression level by 30% at 100 mu M in vitro and by 30% in mouse lung in vivo. Reduced COX- 2 mRNA was attributable to an inhibition of the nuclear factor kappa B ( NF-kappa B) pathway by 10t, 12c- CLA. These data suggested that the inhibition of NF- kappa B was one of the mechanisms for the reduced COX- 2 expression and PGE 2 release by 10t, 12c-CLA.