Regulation of heme oxygenase mRNA in mesangial cells: prostaglandin E2 negatively modulates interleukin-1-induced heme oxygenase-1 mRNA.
Heme oxygenase (EC 1.14.99.3) is the rate-limiting enzyme in heme catabolism. Several lines of evidence suggest a possible role for heme oxygenase in the inflammatory process and in cellular signaling. We have evaluated the regulation of heme oxygenase-1 mRNA induction by the inflammatory stimuli, phorbol 12,13-myristate acetate, heat shock and interleukin-1 beta in cultured rat mesangial cells. Phorbol 12,13-myristate acetate and heat shock rapidly (maximal at 2-3 hrs) induced heme oxygenase-1 mRNA. The effect of interleukin-1 beta on heme oxygenase-1 mRNA induction was slower (maximal at 12 hrs) and modest. However, in the presence of a cyclooxygenase inhibitor, indomethacin, interleukin-1 beta strongly induced heme oxygenase-1 mRNA. The addition of exogenous PGE2 reversed the effect of indomethacin. These data suggest that pro-inflammatory stimuli increase heme oxygenase-1 mRNA expression in rat mesangial cells and that interleukin-1 beta-induced heme oxygenase-1 mRNA level is negatively modulated by PGE2.
Tetsuka
T
T
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Daphna-Iken
D
D
Srivastava
S K
SK
Morrison
A R
AR
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000201:enzymology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007375:Interleukin-1; D012333:RNA, Messenger; D005576:Colforsin; D006419:Heme Oxygenase (Decyclizing); D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin