CLA isomers inhibit TNFalpha-induced eicosanoid release from human vascular smooth muscle cells via a PPARgamma 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-kappaB DNA-binding activity, mRNA levels of inducible enzymes involved in eicosanoid formation (cPLA2, COX-2, mPGES), and the production of the prostaglandins PGE2 and PGI2 by TNFalpha-stimulated SMCs in a dose-dependent manner. The effect of 50 micromol/L of either CLA isomer was as effective as 10 micromol/L of the PPARgamma agonist troglitazone in terms of inhibiting the TNFalpha-stimulated eicosanoid production by SMCs. PPARgamma DNA-binding activity was increased by both CLA isomers compared to control cells. Moreover, it was shown that the PPARgamma antagonist T0070907 partially abrogated the inhibitory action of CLA isomers on cytokine-induced eicosanoid production and NF-kappaB DNA-binding activity by vascular SMCs suggesting that PPARgamma 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.
Ringseis
Robert
R
Institut für Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Emil-Abderhaldenstrasse 26, D-06108 Halle/Saale, Germany. robert.ringseis@landw.uni-halle.de
Müller
André
A
Herter
Christian
C
Gahler
Susan
S
Steinhart
Hans
H
Eder
Klaus
K
D000328:Adult; D001549:Benzamides / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003600:Cytosol / Q000201:enzymology; D015232:Dinoprostone / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000502:physiology; D047495:PPAR gamma / Q000502:physiology*; D010741:Phospholipases A / Q000096:biosynthesis; D011725:Pyridines / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D001549:Benzamides; D002839:Chromans; D044243:Linoleic Acids, Conjugated; D016328:NF-kappa B; D047495:PPAR gamma; D011725:Pyridines; C458508:T 0070907; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; C503589:cis-9, trans-11-conjugated linoleic acid; C496197:trans-10,cis-12-conjugated linoleic acid; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D010741:Phospholipases A; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D000077288:Troglitazone; D015232:Dinoprostone