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 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.
Li
Guangming
G
Molecular and Environmental Toxicology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Barnes
David
D
Butz
Daniel
D
Bjorling
Dale
D
Cook
Mark E
ME
D000818:Animals; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020672:I-kappa B Proteins / Q000187:drug effects; D007536:Isomerism; D019787:Linoleic Acid / Q000494:pharmacology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
D052246:Cyclooxygenase 2 Inhibitors; D020672:I-kappa B Proteins; D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D019787:Linoleic Acid; D015232:Dinoprostone