title: Interleukin-1 beta stimulates cytosolic phospholipase A2 in rheumatoid synovial fibroblasts.
abstract: Phospholipase A2 (PLA2) activities in rheumatoid synovial fibroblasts (RSF) stimulated with interleukin-1 beta (IL-1 beta) were investigated. RSF incubated in the presence of IL-1 beta (120 pg/ml) for 18 h secreted 35 fold more PGE2 than did those incubated without IL-1 beta. IL-1 beta treatment did not increase the level of secretory PLA2 (sPLA2) activity or sPLA2 protein in the conditioned medium or subcellular fractions of lysed RSF. In contrast, the cell-associated PLA2 activity increased 3 to 4 fold in IL-1 beta stimulated RSF when compared with the control. The IL-1 beta stimulated, cell-associated PLA2 required submicromolar concentrations of calcium for activity, a characteristic consistent with the calcium sensitivity of cytosolic PLA2 (cPLA2) activity reported in other cell types, such as U937 cells. These findings demonstrate that an elevation in a cytosolic PLA2, rather than a sPLA2, is associated with increased PGE2 production in IL-1 beta stimulated RSF.
authors.affiliation: Department of Pharmacology, Hoffmann La-Roche Inc., Nutley, NJ 07110.
authors.forename: K I
authors.initials: KI
authors.lastname: Hulkower
authors.forename: W C
authors.initials: WC
authors.lastname: Hope
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.forename: C M
authors.initials: CM
authors.lastname: Anderson
authors.forename: J W
authors.initials: JW
authors.lastname: Coffey
authors.forename: D W
authors.initials: DW
authors.lastname: Morgan
mesh_terms: D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D002458:Cell Fractionation; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011994:Recombinant Proteins / Q000494:pharmacology; D013347:Subcellular Fractions / Q000201:enzymology; D013583:Synovial Membrane / Q000201:enzymology*
chemical_list: D007375:Interleukin-1; D011994:Recombinant Proteins; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone