title: IL-3 and IL-5 enhance the production of LTB4 stimulated by calcium ionophore in rat basophilic leukemia cells.
abstract: To determine the regulatory mechanism of Leukotriene (LT) B4 synthesis by cytokines, we investigated the regulation of LTB4 generation by short-term (30 min) priming and long-term (15 h) enzyme-inducing actions of the four cytokines interleukin (IL)-3, IL-5, tumor necrosis factor alpha (TNF-alpha), and transforming growth factor alpha (TGF-alpha) in rat basophilic leukemia-1 (RBL-1) cells. Pretreatment of cells with IL-3 or IL-5 for 30 min increased A23187- (5x10(-9)M) stimulated synthesis of LTB4 by three to four times over control levels. However, IL-3 or IL-5 lacked this effect when stimulated with exogenous arachidonic acid A at 10(-4)M. TNF-alpha and TGF-alpha had no priming effect on LTB4 synthesis following stimulation with either A23187 (5x10(-9)M) or AA(10(-4)M). Stimulation with the calcium ionophore (A23187)(10(-5)M) or AA(10(-4)M) following 15-h exposure to these cytokines had no effect. These results suggest that IL-3 and IL-5 increase the production of LTB4 by priming the activity of phospholipase A2(PLA2) without inducing enzymes in the arachidonate 5-lipoxygenase pathway. Such a priming effect may be important in regulating the development of allergic and other diseases involving the inflammatory reaction.
authors.affiliation: Department of Pediatrics, Saga Medical School, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: T
authors.initials: T
authors.lastname: Ichimaru
authors.forename: S
authors.initials: S
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D000001:Calcimycin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007377:Interleukin-3 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D015471:Leukemia, Basophilic, Acute; D007975:Leukotriene B4 / Q000096:biosynthesis*; D051381:Rats; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D007377:Interleukin-3; D015848:Interleukin-5; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin; D002118:Calcium