title: Interleukin-1 potentiates bradykinin- and TNF alpha-induced PGE2 release.
abstract: The ability of interleukin-1 (IL-1 alpha), IL-1 beta, tumour necrosis factor alpha (TNF alpha) and bradykinin to cause prostaglandin E2 (PGE2) release from human synovial cells was examined. IL-1 alpha and IL-beta proved equipotent in their effect, and were up to four orders of magnitude more potent than TNF alpha after incubation for 24 h. Bradykinin proved the weakest of all the agonists examined. When the cells were pretreated with IL-1 alpha or IL-1 beta for 24 h, their ability to release PGE2 in response to a short incubation (1 h) with bradykinin, TNF alpha or a second dose of IL-1 was potentiated. In addition, TNF alpha and bradykinin were shown to increase the level of free arachidonic acid (AA) in the cells. Furthermore, a similar potentiation in the response of pretreated cells was observed with exogenous AA. It is already known that pretreatment with IL-1 for 24 h results in an induction of cyclo-oxygenase (CO). It seems likely, therefore, that activation of phospholipase A2 which occurs during a short incubation with IL-1, TNF alpha or bradykinin releases substrate, AA, which is more rapidly converted to PGE2 by cells in which CO has been induced. The result of these events might indicate a sustained release of PGE2 at sites of inflammation where such mediators are released.
authors.affiliation: Department of Pharmacology, Royal College of Surgeons, London, U.K.
authors.forename: L A
authors.initials: LA
authors.lastname: O'Neill
authors.forename: G P
authors.initials: GP
authors.lastname: Lewis
mesh_terms: D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D013582:Synovial Fluid / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D001095:Arachidonic Acids; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D015232:Dinoprostone; D001920:Bradykinin