title: Interleukin-1 and tumor necrosis factor are not synergistic for human synovial fibroblast PLA2 activation and PGE2 production.
abstract: Patterns of arachidonic acid release and metabolism were altered in human synovial fibroblasts following exposure to cytokines. Recombinant interleukin-1 induced an approximate 3-fold increase in [3H]-AA release, a 7-fold increase in PGE2 production and a 2-fold increase in PLA2 activity in human synovial fibroblasts. Recombinant tumor necrosis factor induced similar responses, however, the magnitude was less than that mediated by interleukin-1. A combination of the two cytokines had an additive effect on [3H]-AA release and PLA2 activity while PGE2 production was similar to that detected using interleukin-1 alone. [3H]-AA, was released in substantial amounts when sodium fluoride was used as a stimulus but PGE2 was not. These data show that tumor necrosis factor and interleukin-1 can both activate synovial cell PLA2 and induce generation of PGE2, but act in an additive rather than a synergistic fashion. Furthermore, the data show that PGE2 production is not always concordant with [3H]-AA release, suggesting that appropriate enzyme(s) must be activated.
mesh_terms: D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone; D004347:Drug Interactions; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010003:Osteoarthritis / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011458:Prostaglandins E / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology*; D012016:Reference Values; D013583:Synovial Membrane / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D001095:Arachidonic Acids; D007375:Interleukin-1; D011458:Prostaglandins E; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone