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PMID: 19705266 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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 ·Vol. 32 ·No. 6 ·2009-12-00 ·Pages 364-71

Tsoyi K, Ha YM, Kim YM, Lee YS, Kim HJ, Kim HJ, Seo HG, Lee JH, Chang KC

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.

MeSH Terms
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
Chemicals
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
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Tsoyi Konstantin
Department of Pharmacology, School of Medicine and Institute of Life Sciences, Biomedical Center (BK21), Gyeongsang National University, Jinju 660-751, Korea.
Ha Yu Mi
Kim Young Min
Lee Young Soo
Kim Hyo Jung
Kim Hye Jung
Seo Han Geuk
Lee Jae Heun
Chang Ki Churl
References (28)
28 references, click to expand
  1. Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction.
    Biochem Biophys Res Commun. 2008 Mar 14;367(3):674-9 PMID: 18174021
  2. Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver.
    FASEB J. 2004 May;18(7):854-6 PMID: 15001560
  3. Heme oxygenase-1-derived carbon monoxide enhances the host defense response to microbial sepsis in mice.
    J Clin Invest. 2008 Jan;118(1):239-47 PMID: 18060048
  4. Carbon monoxide-releasing molecules: a pharmacological expedient to counteract inflammation.
    Curr Pharm Des. 2008;14(5):465-72 PMID: 18289073
  5. Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase.
    J Biol Chem. 1994 Feb 18;269(7):4705-8 PMID: 7508926
  6. Prevention of the expression of inducible nitric oxide synthase by a novel positive inotropic agent, YS 49, in rat vascular smooth muscle and RAW 264.7 macrophages.
    Br J Pharmacol. 1999 Sep;128(2):357-64 PMID: 10510445
  7. YS 49, 1-(alpha-naphtylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, regulates angiotensin II-stimulated ROS production, JNK phosphorylation and vascular smooth muscle cell proliferation via the induction of heme oxygenase-1.
    Life Sci. 2008 Mar 12;82(11-12):600-7 PMID: 18262205
  8. Induction of TNF-alpha by LPS in Schwann cell is regulated by MAPK activation signals.
    Cell Mol Neurobiol. 2007 Nov;27(7):909-21 PMID: 17902045
  9. CCAAT/enhancer-binding protein mediates carbon monoxide-induced suppression of cyclooxygenase-2.
    Am J Respir Cell Mol Biol. 2006 Aug;35(2):220-6 PMID: 16543610
  10. The heme oxygenase-1/carbon monoxide pathway suppresses TLR4 signaling by regulating the interaction of TLR4 with caveolin-1.
    J Immunol. 2009 Mar 15;182(6):3809-18 PMID: 19265160
  11. Role of mitogen-activated protein kinase cascades in inducible nitric oxide synthase expression by lipopolysaccharide in a rat Schwann cell line.
    Neurochem Res. 2009 Mar;34(3):430-7 PMID: 18668365
  12. Carbon monoxide protects against ventilator-induced lung injury via PPAR-gamma and inhibition of Egr-1.
    Am J Respir Crit Care Med. 2008 Jun 1;177(11):1223-32 PMID: 18356564
  13. Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation.
    Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2046-50 PMID: 7510883
  14. The CO-releasing molecule CORM-2 is a novel regulator of the inflammatory process in osteoarthritic chondrocytes.
    Rheumatology (Oxford). 2008 Sep;47(9):1323-8 PMID: 18621749
  15. Carbon monoxide-releasing molecule tricarbonyldichlororuthenium (II) dimer induces concentration-dependent alterations in the electrophysiological properties of axons in mammalian spinal cord.
    Neuroscience. 2008 Feb 19;151(4):1104-11 PMID: 18248914
  16. Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli.
    Microbiology (Reading). 2009 Mar;155(Pt 3):813-824 PMID: 19246752
  17. Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages.
    Br J Pharmacol. 2005 Jul;145(6):800-10 PMID: 15880142
  18. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway.
    Nat Med. 2000 Apr;6(4):422-8 PMID: 10742149
  19. Carbon monoxide-releasing molecules: characterization of biochemical and vascular activities.
    Circ Res. 2002 Feb 8;90(2):E17-24 PMID: 11834719
  20. Activation of NFkappaB is necessary for IL-1beta-induced cyclooxygenase-2 (COX-2) expression in human gingival fibroblasts.
    Mol Cell Biochem. 2000 Jun;209(1-2):113-8 PMID: 10942208
  21. A carbon monoxide-releasing molecule (CORM-3) abrogates polymorphonuclear granulocyte-induced activation of endothelial cells and mast cells.
    FASEB J. 2008 Sep;22(9):3380-8 PMID: 18556460
  22. HO-1 and JAK-2/STAT-1 signals are involved in preferential inhibition of iNOS over COX-2 gene expression by newly synthesized tetrahydroisoquinoline alkaloid, CKD712, in cells activated with lipopolysacchride.
    Cell Signal. 2008 Oct;20(10):1839-47 PMID: 18634870
  23. Carbon monoxide orchestrates a protective response through PPARgamma.
    Immunity. 2006 May;24(5):601-10 PMID: 16713977
  24. Role of the soluble guanylyl cyclase alpha1/alpha2 subunits in the relaxant effect of CO and CORM-2 in murine gastric fundus.
    Naunyn Schmiedebergs Arch Pharmacol. 2008 Nov;378(5):493-502 PMID: 18563392
  25. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications.
    Physiol Rev. 2006 Apr;86(2):583-650 PMID: 16601269
  26. Carbon monoxide-releasing antibacterial molecules target respiration and global transcriptional regulators.
    J Biol Chem. 2009 Feb 13;284(7):4516-24 PMID: 19091747
  27. PPARgamma and PPARdelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6712-7 PMID: 12740443
  28. Involvement of anti-inflammatory heme oxygenase-1 in the inhibitory effect of curcumin on the expression of pro-inflammatory inducible nitric oxide synthase in RAW264.7 macrophages.
    Biomed Pharmacother. 2008 Nov;62(9):630-6 PMID: 18325727
Article Info
Journal
Inflammation
Abbr.
Inflammation
ISSN
1573-2576
DOI
10.1007/s10753-009-9144-0
Published
2009-12-00
Pages
364-71
Language
English
Region
United States
NLM ID
7600105
Subset
IM
External Links
PubMed source DOI: 10.1007/s10753-009-9144-0 View journal details
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