Tumor necrosis factor causes amplification of arachidonic acid metabolism in response to interleukin 1, bradykinin, and other agonists.
Tumor necrosis factor stimulated prostaglandin E2 synthesis in Swiss 3T3 fibroblasts. Interleukin 1 also stimulated prostaglandin synthesis. Simultaneous addition of tumor necrosis factor and interleukin 1 synergistically stimulated prostaglandin synthesis, even when both growth factors were added at what would be supramaximal concentrations by themselves. Several small peptides and nonpeptides rapidly stimulate prostaglandin synthesis in these cells. Pretreatment with tumor necrosis factor synergistically enhanced prostaglandin synthesis in response to bradykinin, bombesin, thrombin, norepinephrine, and platelet-activating factor. Thus, tumor necrosis factor stimulates prostaglandin synthesis and greatly amplifies prostaglandin synthesis in response to other agonists. This finding may have significance in chronic inflammatory diseases such as rheumatoid arthritis in which several hormones and growth factors may synergistically augment eicosanoid synthesis.
Burch
R M
RM
Nova Pharmaceutical Corporation, Baltimore, Maryland 21224.
Tiffany
C W
CW
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001839:Bombesin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001095:Arachidonic Acids; D007375:Interleukin-1; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D013917:Thrombin; D015232:Dinoprostone; D001839:Bombesin; D001920:Bradykinin; D009638:Norepinephrine