- 作者: Nian-Chung Yang; Liang-Huei Lu; Yung-Hsi Kao; Lee-Young Chau
- 作者服務機構: Division of Cardiovascular Research Institute of Biomedical Sciences, Academia Sinica, Taipei and Department Life Science, National Central Universtiy, Taoyuan, Taiwan, ROC
- 中文摘要: --
- 英文摘要: Heme oxygenase-1 (HO-1) has been implicated in anti-oxidant and anti-inflammatory actions. To characterizethe role of HO-1 in the vascular inflammatory response,we examined the effect of HO-1 on the expression ofinducible nitric oxide synthase (iNOS) induced by inter-leukin-1 (IL-1 ) in rat vascular smooth muscle cells(VSMCs). Western blot analysis demonstrated that IL-1 -induced iNOS expression was significantly reduced byhemin cotreatment or adenovirus-mediated HO-1 genetransfer. Scavenging carbon monoxide(CO), one of theby-products of heme degradation by HO-1, significantlyattenuated HO-1-mediated suppression of iNOS gene in-duction as revealed by Northern blot analysis. Exposureof cells to CO or a CO donor, the tricarbonyldichlororu-thenium (II) dimer, also markedly inhibited IL-1 -inducediNOS expression. Transient transfection experimentswith a reporter gene construct carrying the rat iNOS genepromoter demonstrated that IL-1 -induced promoter ac-tivity was substantially reduced by cotreatment with COor a CO donor. Furthermore, the effects of CO on iNOSgene promoter activity and protein expression were di-minished by cotreatment with the specific guanylate cy-clase inhibitor, 1 H-[1,2,4]oxadiazolo-(4,3-a)quinoxalin-1-one. These data support the finding that HO-1 attenuatesIL-1 -induced iNOS gene expression in VSMCs.CO ap-pears to mediate the suppressive effect of HO-1, at leastin part, through downregulating transcriptional activa-tion of the iNOS gene via a cGMP-dependent pathway.
- 中文關鍵字: --
- 英文關鍵字: --