出版社:American Society for Biochemistry and Molecular Biology
摘要: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 cyclooxygenase-2 (COX-2). Here, we examined the effects of 10t,12c-CLA and 9c,11t-CLA on COX-2 protein/mRNA expression, prostaglandin E2 (PGE2) 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 μM in vitro. PGE2 production was decreased from 5.39 to 1.12 ng/2 × 106 cells by 10t,12c-CLA and from 5.7 to 4.5 ng/2 × 106 cells by 9c,11t-CLA at 100 μM. 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 PGE2 release in the lung. 10t,12c-CLA reduced COX-2 mRNA expression level by 30% at 100 μM in vitro and by 30% in mouse lung in vivo. Reduced COX-2 mRNA was attributable to an inhibition of the nuclear factor κB (NF-κB) pathway by 10t,12c-CLA. These data suggested that the inhibition of NF-κB was one of the mechanisms for the reduced COX-2 expression and PGE2 release by 10t,12c-CLA.