On the signal transducing mechanisms involved in the synergistic interaction between interleukin-1 and bradykinin on prostaglandin biosynthesis in human gingival fibroblasts.
Recombinant human interleukin-1 beta (IL-1 beta) and bradykinin (BK) synergistically stimulate prostaglandin E2 (PGE2) formation in human gingival fibroblasts cultured for 24 h. Neither BK or IL-1 beta per se, nor their combinations, caused any acute stimulation of cellular cyclic AMP accumulation. BK, but not IL-1 beta, caused a rapid, transient rise of intracellular Ca2+ concentration ([Ca2+]i), as assessed by recordings of fura-2 fluorescence in monolayers of prelabelled gingival fibroblasts. IL-1 beta did not change the effect of BK on [Ca2+]i. Ionomycin and A23187, two calcium ionophores, synergistically potentiated the stimulatory effect of IL-1 beta on PGE2 formation. Three different phorbol esters known to activate protein kinase C also synergistically potentiated the action of IL-1 beta on PGE2 formation. Exogenously added arachidonic acid significantly enhanced the basal formation of PGE2. In IL-1 beta treated cells, the enhancement of PGE2 formation seen after addition of arachidonic acid, was synergistically upregulated by IL-1 beta. These data show that i) the synergistic interaction between IL-1 beta and BK on PGE2 formation is not due to an effect linked to an upregulation of cyclic AMP or [Ca2+]i; ii) the signal transducing mechanism by which BK interacts with IL-1 beta, however, may be linked to a BK induced stimulation of [Ca2+]i and/or protein kinase C; iii) the mechanism involved in the action of IL-1 beta may, at least partly, be due to enhancement of the biosynthesis of prostanoids mediated by an upregulation of cyclooxygenase activity.
Lerner
U H
UH
Department of Oral Cell Biology, University of Umeå, Sweden.
Brunius
G
G
Modeer
T
T
D016718:Arachidonic Acid / Q000494:pharmacology; D001920:Bradykinin / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis*; D004357:Drug Synergism; D004789:Enzyme Activation; D005881:Gingiva / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology*; D007476:Ionophores / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D018002:Receptors, Bradykinin; D017472:Receptors, Interleukin-1 / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000502:physiology; D015290:Second Messenger Systems; D015398:Signal Transduction
D007375:Interleukin-1; D007476:Ionophores; D010703:Phorbol Esters; D018002:Receptors, Bradykinin; D017472:Receptors, Interleukin-1; D017981:Receptors, Neurotransmitter; D016718:Arachidonic Acid; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium