IL-1 beta amplifies bradykinin-induced prostaglandin E2 production via a phospholipase D-linked mechanism

• Published in: The Journal of immunology (1950) Vol. 152; no. 10; pp. 5032 - 5040
• Main Authors: Angel, J, Audubert, F, Bismuth, G, Fournier, C
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.05.1994; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Bradykinin - pharmacology; Cells, Cultured; Diglycerides - biosynthesis; Dinoprostone - biosynthesis; Drug Synergism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Interleukin-1 - pharmacology; Lymphokines, interleukins ( function, expression); Phospholipase D - physiology; Regulatory factors and their cellular receptors; Synovial Membrane - cytology; Synovial Membrane - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Type C Phospholipases - physiology; Human; Enzyme; Arachidonic acid derivatives; Cytokine; Prostaglandin E2; Interleukin 1β; Stimulation; Esterases; Biosynthesis; Phosphoric diester hydrolases; Synergism; Phospholipase D; Bradykinin; Phosphatidylcholine; Hydrolases
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.152.10.5032

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.