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

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13 引文 斯高帕斯(Scopus)


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.
頁(從 - 到)1520-1525
期刊International Immunopharmacology
出版狀態已發佈 - 12月 2010

ASJC Scopus subject areas

  • 免疫學
  • 免疫學和過敏
  • 藥理


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