Carbon monoxide induces cyclooxygenase-2 expression through MAPKs and PKG in phagocytes

Li Ching Lin, Feng Ming Ho, Shish Jung Yen, Pei Yi Wu, Ling Fang Hung, Wei Jan Huang, Yu Chih Liang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Many biological functions of heme oxygenase (HO) have been attributed to its enzymatic byproduct carbon monoxide (CO). CO has been demonstrated to play an important role in down-regulation of pro-inflammatory cytokines, but few studies have investigated the effects of CO on the cyclooxygenase-2 (COX-2) expression in macrophage. Here, we assessed the induction of COX-2 by CO in macrophage with or without lipopolysaccharide (LPS) stimulation. Tricarbonyldichloro ruthenium (II) dimmer (CORM-2) is a well known CO-releasing molecule, and exhibits anti-inflammatory activity in several cell types. In this study, both CORM-2 and CO gas were used to investigate the induction of COX-2 and the underlying molecular mechanisms in macrophage. Western blot and RT-PCR analysis demonstrated that CORM-2 and CO gas (500 ppm) significantly inhibited the protein and mRNA expression of iNOS in LPS-activated macrophages. In contrast, CORM-2 and CO gas up-regulated COX-2 expression and prostaglandin E2 (PGE2) production in the macrophage with or without LPS. CORM-2 time-dependently induced the phosphorylation of Akt and MAPKs, and the induction of COX-2 could be blocked by Akt, PKG, and MAPKs inhibitors. Indomethacin was used to decrease CORM-2-induced PGE2 production by inhibiting COX-2 enzyme activity. Indomethacin was unable to reverse the decrease of iNOS, but it could restore the IL-1β expression and decrease the IL-10 expression in CORM-2-treated cells. The results suggest that CO induced COX-2 expression and PGE2 production through activating the Akt, PKG, and MAPK pathways, and CO-induced PGE2 may modulate inflammation during macrophage activation by suppressing IL-1β expression and inducing IL-10 production.

Original languageEnglish
Pages (from-to)1520-1525
Number of pages6
JournalInternational Immunopharmacology
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Carbon monoxide
  • Cyclooxygenase-2
  • Inflammation
  • Macrophage
  • Prostaglandin E

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

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