Downregulation of the Human Heme Oxygenase Gene by Glucocorticoids and Identification of 56b Regulatory Elements

• Published in: Biochemical and biophysical research communications Vol. 218; no. 3; pp. 759 - 765
• Main Authors: Lavrovsky, Yan, Drummond, George S., Abraham, Nader G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.01.1996
• Subjects: Acute-Phase Reaction; Animals; Base Sequence; Dexamethasone - pharmacology; Down-Regulation; Gene Expression Regulation, Enzymologic - drug effects; Glucocorticoids - pharmacology; Heme Oxygenase (Decyclizing) - genetics; Humans; Interleukin-6 - pharmacology; Molecular Sequence Data; Promoter Regions, Genetic; Rabbits; RNA, Messenger - genetics; Transcription Factors - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1996.0135

Several human heme oxygenase-1 promoter-driven chloramphenicol acetyltransferase constructs were examined in order to analyze promoter activity of the heme oxygenase-1 gene in microvessel endothelial cells. Heme oxygenase promoter activity was up-regulated by interleukin-6. This induction was shown to be down-regulated by glucocorticoids. Chloramphenicol acetyltransferase assays revealed that the promoter region (56 base pair) between −180 and −120 was responsible for up-regulation by growth factors, as well as for glucocorticoid-directed down-regulation. The same DNA fragment was shown to bind nuclear factor(s) from endothelial cells treated with dexamethasone. Formation of DNA protein complexes peaked after a 6-hour treatment. The DNA fragment was found to contain a sequence recognized by the STAT 3/acute phase response factor.