Heme oxygenase-1 attenuates interleukin-1 β-induced nitric oxide synthase expression in vascular smooth muscle cells

Nian Chung Yang, Liang Huei Lu, Yung Hsi Kao, Lee Young Chau

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24 Scopus citations

Abstract

Heme oxygenase-1 (HO-1) has been implicated in antioxidant and anti-inflammatory actions. To characterize the role of HO-1 in the vascular inflammatory response, we examined the effect of HO-1 on the expression of inducible nitric oxide synthase (iNOS) induced by interleukin-1β (IL-1β) in rat vascular smooth muscle cells (VSMCs). Western blot analysis demonstrated that IL-1β-induced iNOS expression was significantly reduced by hemin cotreatment or adenovirus-mediated HO-1 gene transfer. Scavenging carbon monoxide (CO), one of the by-products of heme degradation by HO-1, significantly attenuated HO-1-mediated suppression of iNOS gene induction as revealed by Northern blot analysis. Exposure of cells to CO or a CO donor, the tricarbonyldichlororuthenium(II) dimer, also markedly inhibited IL-1β-induced iNOS expression. Transient transfection experiments with a reporter gene construct carrying the rat iNOS gene promoter demonstrated that IL-1β-induced promoter activity was substantially reduced by cotreatment with CO or a CO donor. Furthermore, the effects of CO on iNOS gene promoter activity and protein expression were diminished by cotreatment with the specific guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-(4,3-a)quinoxalin-1-one. These data support the finding that HO-1 attenuates IL-1β-induced iNOS gene expression in VSMCs. CO appears to mediate the suppressive effect of HO-1, at least in part, through downregulating transcriptional activation of the iNOS gene via a cGMP-dependent pathway.

Original languageEnglish
Pages (from-to)799-809
Number of pages11
JournalJournal of Biomedical Science
Volume11
Issue number6
DOIs
StatePublished - 2004

Keywords

  • Carbon monoxide
  • Heme oxygenase-1
  • Interleukin-1β
  • Nitric oxide synthase
  • Smooth muscle cells

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