Activation of PPAR-gamma by carbon monoxide from CORM-2 leads to the inhibition of iNOS but not COX-2 expression in LPS-stimulated macrophages.
The effect of CO on the expression of iNOS and COX-2 was investigated by using a CO-releasing molecule (CORM)-2 in LPS-activated RAW 264.7 cells in vitro. Interestingly, CORM-2 significantly inhibited iNOS (NO) but not COX-2 (PGE(2)) expression. PPAR-gamma activators such as troglitazone, GW1929, and 15-deoxy-Delta12, 14- prostaglandin J(2) showed preferential inhibitory effect on iNOS over COX-2 expression in LPS-activated macrophages. The same effect was shown in lung tissues (iNOS, COX-2) and serum (NO, PGE(2)) when administered of CORM-2 in LPS-induced septic mice, indicating that CO derived from CORM-2 differentially regulates iNOS and COX-2 through PPAR-gamma activation under inflammation state.
Tsoyi
Konstantin
K
Department of Pharmacology, School of Medicine and Institute of Life Sciences, Biomedical Center (BK21), Gyeongsang National University, Jinju 660-751, Korea.
Ha
Yu Mi
YM
Kim
Young Min
YM
Lee
Young Soo
YS
Kim
Hyo Jung
HJ
Kim
Hye Jung
HJ
Seo
Han Geuk
HG
Lee
Jae Heun
JH
Chang
Ki Churl
KC
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology*; D047495:PPAR gamma / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009942:Organometallic Compounds; D047495:PPAR gamma; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
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