On the signal transducing mechanisms involved in the synergistic interaction between interleukin-1 and bradykinin on prostaglandin biosynthesis in human gingival fibroblasts Available to Purchase

Recombinant human interleukin-1β (IL-1β) and bradykinin (BK) synergistically stimulate prostaglandin E₂ (PGE₂) formation in human gingival fibroblasts cultured for 24 h. Neither BK or IL-1β per se, nor their combinations, caused any acute stimulation of cellular cyclic AMP accumulation. BK, but not IL-1β, 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-1β did not change the effect of BK on [Ca²⁺]_i. Ionomycin and A 23187, two calcium ionophores, synergistically potentiated the stimulatory effect of IL-1β on PGE₂ formation. Three different phorbol esters known to activate protein kinase C also synergistically potentiated the action of IL-1β on PGE₂ formation. Exogenously added arachidonic acid significantly enhanced the basal formation of PGE₂. In IL-1β treated cells, the enhancement of PGE₂ formation seen after addition of arachidonic acid, was synergistically upregulated by IL-1β. These data show that i) the synergistic interaction between IL-1β 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-1β, 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-1β may, at least partly, be due to enhancement of the biosynthesis of prostanoids mediated by an upregulation of cyclooxygenase activity.