Enhancement of tumor necrosis factor-alpha gene expression by low doses of prostaglandin E2 and cyclic GMP.
Macrophage-derived PGE2 is usually considered to be a down-regulator of TNF-alpha production. However, we recently demonstrated that PGE2 may display dual activities in that low concentrations stimulated whereas higher doses suppressed TNF-alpha synthesis in resident peritoneal macrophages. To examine the underlying molecular mechanisms, we studied TNF-alpha gene expression in rat peritoneal macrophages and the murine PU5-1.8 macrophage line. In both macrophage types, PGE2 enhanced TNF-alpha gene transcription and production at an optimal concentration of 1 ng/ml. Furthermore, evidence was obtained that PGE2 may stimulate TNF-alpha mRNA accumulation via a rise of the intracellular messenger cGMP. Both, exogenously added as well as endogenously, by sodium nitroprusside generated cGMP were found to enhance TNF-alpha gene expression and production. These findings lend further support to the concept that cGMP may represent one of the positive signals for TNF-alpha synthesis.
Gong
J H
JH
Institute of Immunology, Philipps University, Marburg, Germany.
Renz
H
H
Sprenger
H
H
Nain
M
M
Gemsa
D
D
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D009599:Nitroprusside / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015290:Second Messenger Systems; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D006152:Cyclic GMP; D015232:Dinoprostone