CLA isomers inhibit TNFα-induced eicosanoid release from human vascular smooth muscle cells via a PPAR-γ ligand-like action

Conjugated linoleic acids (CLAs) were reported to have anti-atherogenic properties in animal feeding experiments. In an attempt to elucidate the molecular mechanisms of these anti-atherogenic effects, the modulatory potential of CLA on cytokine-induced eicosanoid production from smooth muscle cells (SMCs), which contributes to the chronic inflammatory response associated with atherosclerosis, has been investigated in the present study. cis-9, trans-11 CLA and trans-10, cis-12 CLA were shown to reduce proportions of the eicosanoid precursor arachidonic acid in SMC total lipids and to inhibit cytokine-induced NF-kappa B DNA-binding activity, mRNA levels of inducible enzymes involved in eicosanoid formation (cPLA(2), COX-2, mPGES), and the production of the prostaglandins PGE(2) and PGI(2) by TNF alpha-stimulated SMCs in a dose-dependent manner. The effect of 50 mu mol/L of either CLA isomer was as effective as 10 mu mol/L of the PPAR gamma agonist troglitazone in terms of inhibiting the TNF alpha-stimulated eicosanoid production by SMCs. PPAR gamma DNA-binding activity was increased by both CLA isomers compared to control cells. Moreover, it was shown that the PPAR gamma antagonist T0070907 partially abrogated the inhibitory action of CLA isomers on cytokine-induced eicosanoid production and NF-kappa B DNA-binding activity by vascular SMCs suggesting that PPAR gamma signalling is at least partially involved in the action of CLA in human vascular SMCs. With respect to the effects of CLA on experimental atherosclerosis, our findings suggest that the anti-inflammatory effect of CLA is at least partially responsible for the anti-atherogenic effects of CLA observed in vivo. (c) 2005 Elsevier B.V. All rights reserved.