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.

Abstract

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.

• Authors: Konstantin Tsoyi, Yu Mi Ha, Young Min Kim, Young Soo Lee, Hyo Jung Kim, Hye Jung Kim, Han Geuk Seo, Jae Heun Lee, Ki Churl Chang
• Journal: Inflammation (Inflammation) Vol. 32 Issue 6 Pg. 364-71 (Dec 2009) ISSN: 1573-2576 [Electronic] United States
• PMID: 19705266 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Lipopolysaccharides
• Organometallic Compounds
• PPAR gamma
• tricarbonyldichlororuthenium (II) dimer
• Carbon Monoxide
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Ptgs2 protein, mouse
• Cyclooxygenase 2

Topics

• Animals
• Carbon Monoxide (pharmacology)
• Cell Line
• Cyclooxygenase 2 (biosynthesis)
• Endotoxemia (chemically induced, metabolism, pathology)
• Enzyme Inhibitors (metabolism, pharmacology)
• Gene Expression Regulation, Enzymologic (drug effects)
• Lipopolysaccharides (physiology)
• Macrophages, Alveolar (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Nitric Oxide Synthase Type II (antagonists & inhibitors, biosynthesis)
• Organometallic Compounds (metabolism, pharmacology)
• PPAR gamma (metabolism)