Regulation of prostaglandin endoperoxide synthase gene expression in rat mesangial cells by interleukin-1 beta.
In primary cultures of rat mesangial cells from passage 3 to 6, interleukin-1 beta (IL-1) induced a time-dependent increase in prostaglandin E2 (PGE2) formation and release into the extracellular medium. This increase was associated with a dramatic upregulation of the steady-state levels of mRNA for the prostaglandin endoperoxide synthetase (PES)-2 gene transcript as demonstrated by Northern analysis. In contrast, there did not appear to be a significant increase in the mRNA levels for a 2.8-kb transcript for the PES-1 gene. At 18 h of exposure to IL-1, the steady-state level of message for PES-2 remained elevated at 50% of the 2-h time point. Culturing the cells in the presence of cycloheximide and IL-1 demonstrated a superinduction of the PES-2 message without any change in PES-1 message. The tumor-promoting phorbol ester, phorbol myristate acetate (PMA), was also associated with an upregulation of the message for the PES-2 gene and did not influence the levels of the message for the PES-1 gene as demonstrated by Northern analysis. Dexamethasone (Dex) inhibited to control levels the induction by PMA, but the induction of the message by IL-1 was only inhibited 30%. Despite 70% of the message being present by 2 h of induction, Dex was capable of totally inhibiting the inductive effect of IL-1 with respect to PGE2 biosynthesis. Immunocytochemical studies demonstrated a dramatic induction of PES-2 protein by IL-1, which was inhibited by Dex. The data suggest that Dex inhibits the translation of the PES-2 protein.
Rzymkiewicz
D
D
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Leingang
K
K
Baird
N
N
Morrison
A R
AR
D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D012333:RNA, Messenger; D003907:Dexamethasone; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate