Tumor necrosis factor causes amplification of arachidonic acid metabolism in response to interleukin 1, bradykinin, and other agonists. 1989

R M Burch, and C W Tiffany
Nova Pharmaceutical Corporation, Baltimore, Maryland 21224.

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.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010741 Phospholipases A Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D011451 Prostaglandin-Endoperoxide Synthases Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor. Fatty Acid Cyclo-Oxygenase,PGH Synthase,Prostaglandin H Synthase,Prostaglandin Synthase,Prostaglandin-Endoperoxide Synthase,Arachidonic Acid Cyclooxygenase,Cyclo-Oxygenase,Cyclooxygenase,Cyclooxygenases,Hydroperoxide Cyclase,PGH2 Synthetase,Prostaglandin Cyclo-Oxygenase,Prostaglandin Cyclooxygenase,Prostaglandin Endoperoxide Synthetase,Prostaglandin G-H Synthase,Prostaglandin H2 Synthetase,Prostaglandin Synthetase,Cyclase, Hydroperoxide,Cyclo Oxygenase,Cyclo-Oxygenase, Fatty Acid,Cyclo-Oxygenase, Prostaglandin,Cyclooxygenase, Arachidonic Acid,Cyclooxygenase, Prostaglandin,Endoperoxide Synthetase, Prostaglandin,Fatty Acid Cyclo Oxygenase,G-H Synthase, Prostaglandin,Prostaglandin Cyclo Oxygenase,Prostaglandin Endoperoxide Synthases,Prostaglandin G H Synthase,Synthase, PGH,Synthase, Prostaglandin,Synthase, Prostaglandin G-H,Synthase, Prostaglandin H,Synthase, Prostaglandin-Endoperoxide,Synthases, Prostaglandin-Endoperoxide,Synthetase, PGH2,Synthetase, Prostaglandin,Synthetase, Prostaglandin Endoperoxide,Synthetase, Prostaglandin H2
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D001839 Bombesin A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function. Bombesin 14,Bombesin Dihydrochloride,Dihydrochloride, Bombesin
D001920 Bradykinin A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg,Bradykinin Acetate, (9-D-Arg)-Isomer,Bradykinin Diacetate,Bradykinin Hydrochloride,Bradykinin Triacetate,Bradykinin, (1-D-Arg)-Isomer,Bradykinin, (2-D-Pro)-Isomer,Bradykinin, (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (2-D-Pro-7-D-Pro)-Isomer,Bradykinin, (3-D-Pro)-Isomer,Bradykinin, (3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (5-D-Phe)-Isomer,Bradykinin, (5-D-Phe-8-D-Phe)-Isomer,Bradykinin, (6-D-Ser)-Isomer,Bradykinin, (7-D-Pro)-Isomer,Bradykinin, (8-D-Phe)-Isomer,Bradykinin, (9-D-Arg)-Isomer,Arg Pro Pro Gly Phe Ser Pro Phe Arg
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.

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