Regulation of heme oxygenase-1 expression in vivo and in vitro in hyperoxic lung injury.

Journal Article (Journal Article)

Using hyperoxia as a model of oxidant-induced lung injury in the rat, we explored the regulation of heme oxygenase-1 (HO-1) expression in vivo and in vitro. We demonstrate marked increase of HO-1 messenger ribonucleic acid (mRNA) levels in rat lungs after hyperoxia. Increased HO-1 mRNA expression correlated with increased HO-1 protein and enzyme activity. Immunohistochemical studies of the rat lung after hyperoxia showed increased HO-1 expression in a variety of cell types, including the bronchoalveolar epithelium and interstitial and inflammatory cells. We then examined the regulation of HO-1 expression in vitro after hyperoxia and observed increased HO-1 gene expression in various cultured cells including epithelial cells, fibroblasts, macrophages, and smooth muscle cells. Increased HO-1 mRNA expression correlated with increased HO-1 protein in vitro, and resulted from increased gene transcription and not from increased mRNA stability. We show that transcriptional activation of the HO-1 gene by hyperoxia requires cooperation between the HO-1 promoter and an enhancer fragment located 4 kb upstream from its transcription site. Increased HO-1 gene transcription was associated with increased activator protein-1 (AP-1) binding activity and supershift of the AP-1 complex by antibodies to c-Fos and c-Jun after hyperoxia. Taken together, our data suggest that AP-1 activation may represent one mechanism mediating hyperoxia-induced HO-1 gene transcription.

Full Text

Duke Authors

Cited Authors

  • Lee, PJ; Alam, J; Sylvester, SL; Inamdar, N; Otterbein, L; Choi, AM

Published Date

  • June 1996

Published In

Volume / Issue

  • 14 / 6

Start / End Page

  • 556 - 568

PubMed ID

  • 8652184

International Standard Serial Number (ISSN)

  • 1044-1549

Digital Object Identifier (DOI)

  • 10.1165/ajrcmb.14.6.8652184

Language

  • eng

Conference Location

  • United States