IL-1 beta amplifies bradykinin-induced prostaglandin E2 production via a phospholipase D-linked mechanism.
The proinflammatory cytokine IL-1 was shown to increase the responsiveness of synovial cells to the potent inflammatory peptide bradykinin (BK). We have investigated the biochemical events linked to this amplifying action of IL-1. Stimulation of synoviocytes with only BK elicited a rapid increase in inositol phosphates and a concomitant accumulation of diacylglycerol (DAG), monoacylglycerol, and free arachidonic acid (AA). In contrast, IL-1 did not stimulate any of these events. Thus, BK can induce AA release via the hydrolysis of phosphatidylinositols by a phospholipase C (PLC). BK also activated a phospholipase D (PLD) to cleave phosphatidylcholine (PC), because it caused an increase in phosphatidic acid (PA) content and a sustained DAG formation, which both were inhibited by ethanol in [3H]myristic acid-labeled cells. Moreover, the addition of ethanol diverted PLD into the formation of phosphatidylethanol (PEt) thus inhibiting the amounts of PA and DAG formed. Priming of synovial cells with rIL-1 beta 24 h before exposure to BK in the presence of ethanol further enhanced the BK-induced formation of PEt. Conversely, preincubation with IL-1 did not influence the BK-induced PLC activation nor did it alter the liberation of AA. Finally, we demonstrated that the IL-1-mediated amplification of PGE2 release in response to BK was reduced by the presence of ethanol in the culture medium, suggesting that part of the synergistic action of IL-1 and BK on prostanoid production was dependent on the activation of the PC-specific PLD pathway.
Angel
J
J
INSERM U 283, Cochin Hospital, Paris, France.
Audubert
F
F
Bismuth
G
G
Fournier
C
C
D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D004075:Diglycerides / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis*; D004357:Drug Synergism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010739:Phospholipase D / Q000502:physiology*; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology
D004075:Diglycerides; D007375:Interleukin-1; D010738:Type C Phospholipases; D010739:Phospholipase D; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin