Stimulation of macrophage prostaglandin and neutral protease production by phorbol esters as a model for the induction of vascular changes associated with tumor promotion.
A series of phorbol esters stimulates prostaglandin E production from both resident and starch-induced mouse peritoneal macrophages. The relative potencies of these compounds parallel their abilities both to elevate macrophage plasminogen activator levels and to function as tumor promoters in a mouse skin carcinogenesis model. Low concentrations of antiinflammatory glucocorticoids, such as dexamethasone, inhibit the enhanced prostaglandin E synthesis as a result of 12-O-tetradecanoylphorbol-13-acetate action. The same glucocorticoids also inhibit the enhanced plasminogen activator production. On the basis of these observations, it is suggested that there might be a relationship between macrophage phospholipase activation and plasminogen activator synthesis. It is also suggested that these data might be providing insight into how 12-O-tetradecanoylphorbol-13-acetate and certain structural analogs elicit an inflammatory response and behave as tumor promoters in mouse skin.
D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010447:Peptide Hydrolases / Q000096:biosynthesis*; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors / Q000378:metabolism; D015849:Plasminogen Inactivators; D011458:Prostaglandins E / Q000096:biosynthesis*; D013268:Stimulation, Chemical
D010703:Phorbol Esters; D010704:Phorbols; D015849:Plasminogen Inactivators; D011458:Prostaglandins E; D003907:Dexamethasone; D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D007213:Indomethacin