Downregulation of the human heme oxygenase gene by glucocorticoids and identification of 56b regulatory elements.
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 fragments 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.
Lavrovsky
Y
Y
Rockefeller University, New York, New York 10021, USA.
Drummond
G S
GS
Abraham
N G
NG
D000210:Acute-Phase Reaction; D000818:Animals; D001483:Base Sequence; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D014157:Transcription Factors / Q000502:physiology*
D005938:Glucocorticoids; D015850:Interleukin-6; D012333:RNA, Messenger; D014157:Transcription Factors; D003907:Dexamethasone; D006419:Heme Oxygenase (Decyclizing)