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

Inflammation. 2009 Dec;32(6):364-71. doi: 10.1007/s10753-009-9144-0.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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