Interleukin-1 and tumor necrosis factor are not synergistic for human synovial fibroblast PLA2 activation and PGE2 production.
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.
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*
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