Differentiation-associated expression of prostaglandin G/H synthase in monocytic cells.
Significant progress in the investigation of the regulation of prostanoid formation has recently been made by cloning a second gene coding for prostaglandin G/H synthase (PGHS; EC 1.14.99.1). In this study we examined the expression of the two PGHS isoforms during phorbol ester induced monocytic differentiation of human myeloid leukemia cells (U937). Murine and ovine PGHS-1 probes hybridized to 2.8- and 5.5-kb mRNA species, whereas the murine PGHS-2 probe hybridized to a 5.3-kb species. Western blot analysis using antisera to mouse PGHS-1 and to a synthetic peptide derived from a mouse PGHS-2-specific region revealed a band of 70 kDa for PGHS-1 and a doublet of about 85 kDa for PGHS-2. Unlike PGHS-2, which was not expressed in U937 control cells, both PGHS-1 protein and mRNA were detected in untreated U937 cells. TPA strongly induced PGHS-2 protein and also increased the amount of PGHS-1 protein. Correspondingly, a marked induction of PGHS-2 mRNA was found, but virtually no change in the expression of the PGHS-1 2.8-kb mRNA occurred. The induction of both PGHS isoforms turned out to be dexamethasone-sensitive. The suppression of PGHS-2 induction was more pronounced. These results suggest that both PGHS-1 and to a larger extent PGHS-2 contribute to the upregulation of prostanoid synthesis during monocytic differentiation.
Hoff
T
T
Institute of Molecular Pharmacology, Medical School Hannover, Germany.
DeWitt
D
D
Kaever
V
V
Resch
K
K
Goppelt-Struebe
M
M
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007951:Leukemia, Myeloid; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012756:Sheep; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D013755:Tetradecanoylphorbol Acetate