10t,12c-conjugated linoleic acid inhibits lipopolysaccharide-induced cyclooxygenase expression in vitro and in vivo

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 [micro]M in vitro. PGE₂ production was decreased from 5.39 to 1.12 ng/2 x 10⁶ cells by 10t,12c-CLA and from 5.7 to 4.5 ng/2 x 10⁶ cells by 9c,11t-CLA at 100 [micro]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 PGE₂ release in the lung. 10t,12c-CLA reduced COX-2 mRNA expression level by 30% at 100 [micro]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 PGE₂ release by 10t,12c-CLA.