Suppression of cyclooxygenase-2 and inducible nitric oxide synthase expression by conjugated linoleic acid in murine macrophages.
Activated macrophages express inducible isoforms of cyclooxygenase (COX-2) and nitric oxide synthase (iNOS), and produce excessive amounts of prostaglandin E(2) (PGE(2)) and nitric oxide (NO) which play key roles in cancer pathogenesis. Conjugated linoleic acid (CLA) is an anticarcinogen while arachidonic acid (AA) may be a procarcinogen by increased PGE(2) production. This study examined the effects of CLA and AA on PGE(2) and NO synthesis in endotoxin-activated macrophages. RAW264.7 macrophages were incubated in medium containing no added lipid (control), 30 microM AA (AA medium), or 30 microM CLA (CLA medium) for 24 h followed by activation with bacterial endotoxin lipopolysaccharide (LPS; 100 ng/ml) for 9 h. CLA significantly depressed PGE(2) and NO production by 78% (P=0.003) and 57% (P=0.0001) respectively. Northern blot analysis of COX-2 and iNOS showed significant 33% (P=0.01) and 51% (P=0.04) decreases, respectively, paralleling those seen for PGE(2) and NO production. In contrast, AA significantly increased PGE(2) synthesis by 62% (P=0.02) and also suppressed NO production and iNOS expression in the same manner as observed for CLA. These results suggest that the anticarcinogenic effect of CLA in endotoxin-activated macrophages may be related to its ability to decrease both PGE(2) and NO synthesis by suppressing transcription of COX-2 and iNOS.
Iwakiri
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Y
Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523, USA.
Sampson
D A
DA
Allen
K G D
KG
D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007527:Isoenzymes / Q000235:genetics*; D019787:Linoleic Acid / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D007527:Isoenzymes; D012333:RNA, Messenger; D009569:Nitric Oxide; D019787:Linoleic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone