{'fraction_non_alphanumeric': 0.04220183486238532, 'fraction_numerical': 0.014678899082568808, 'mean_word_length': 5.292307692307692, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Heme Oxygenase-1 Attenuates Interleukin-1β-Induced Nitric Oxide Synthase Expression in Vascular Smooth Muscle Cells

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.