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J. Lipid Res.
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A more recent version of this article appeared on October 1, 2005

Papers In Press, published online ahead of print August 1, 2005
J. Lipid Res., doi:10.1194/jlr.M500064-JLR200
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Submitted on February 18, 2005
Revised on July 20, 2005
Accepted on July 27, 2005

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

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

University of Wisconsin-Madison, Madison, Wisconsin 53706

Corresponding Author: mcook{at}wisc.edu

Previous data demonstrated CLA reduced eicosanoid release from select organs. We hypothesized that one active CLA isomer was responsible for the reduced prostaglandin release and the mechanism was through the inhibition of inducible cyclooxygenase (COX-2). Here we examined 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. COX-2 protein expression level was inhibited 80% by 10t, 12c-CLA and 26% by 9c, 11t-CLA at 100 µM in vitro. PGE2 production was decreased from 5.39 ng to 1.12 ng/2×106 cells by 10t, 12c-CLA and from 5.7 ng to 4.5 ng/2×106 cells by 9c, 11t-CLA at 100 µM. 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 µM in vitro and 30% in mice lung in vivo. Reduced COX-2 mRNA was due to an inhibition of NF-B pathway by 10t, 12c-CLA. The data suggested inhibition of NF-B was one of the mechanisms for the reduced COX-2 expression and PGE2 release by 10t, 12c-CLA.


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