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

Guangming Li,David Barnes,Daniel Butz,Dale Bjorling,Mark E Cook

doi:10.1194/jlr.m500064-jlr200

Guangming Li, David Barnes + Show 3 more

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https://doi.org/10.1194/jlr.m500064-jlr200

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Abstract

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 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 microM 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 microM. 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 microM in vitro and by 30% in mouse lung in vivo. Reduced COX-2 mRNA was attributable to an inhibition of the nuclear factor kappaB (NF-kappaB) pathway by 10t,12c-CLA. These data suggested that the inhibition of NF-kappaB was one of the mechanisms for the reduced COX-2 expression and PGE(2) release by 10t,12c-CLA.

Highlights

Previous data demonstrated that conjugated linoleic acid (CLA) reduced eicosanoid release from select organs
We found that 10t,12c-CLA was the isomer that inhibited COX-2 protein, mRNA level, and prostaglandin E2 (PGE2) release both in vitro and in vivo
After Raw264.7 macrophages were incubated with LA, 10t,12c-CLA, or 9c,11t-CLA isomers for 24 h and stimulated with LPS (100 ng/ml) for 8 h, cell viability exceeded 96%

Summary

Introduction

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). Reduced COX-2 mRNA was attributable to an inhibition of the nuclear factor ␬B (NF-␬B) pathway by 10t,12c-CLA These data suggested that the inhibition of NF-␬B was one of the mechanisms for the reduced COX-2 expression and PGE2 release by 10t,12cCLA.—Li, G., D. 10t,12c-conjugated linoleic acid inhibits lipopolysaccharide-induced cyclooxygenase expression in vitro and in vivo. Mixed or purified isomers of CLA have been demonstrated to inhibit inducible isoforms of cyclooxygenase (COX) mRNA and protein expression in vitro [19,20,21]. Because COX-2 has been shown to play a significant role in many inflammatory diseases, it has been an important pharmacological target for the prevention and/or treatment of arthritis and cancer [23]

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