Bradykinin potentiates prostaglandin E2 release in the human gingival fibroblasts pretreated with interleukin-1β via Ca2+ mobilization

Interleukin-1 beta, a proinflammatory cytokine, causes a slow increase in prostaglandin E-2 release. On the other hand, bradykinin, a chemical mediator for inflammation, induces a rapid prostaglandin E-2 release. Simultaneous stimulation with interleukin-1 beta (200 pg/ml) and bradykinin (1 mu M) evoked a moderately synergistic increase in prostaglandin E-2 release in human gingival fibroblasts. However, in the human gingival fibroblasts pretreated with interleukin-1 beta, bradykinin drastically enhanced prostaglandin E-2 release. NS-398, a specific inhibitor of cyclooxygenase-2, inhibited not only interleukin-1 beta-induced prostaglandin E-2 release but also bradykinin-induced prostaglandin E-2 release in the human gingival fibroblasts pretreated with interleukin-1 beta. Transcriptional and translational inhibitors such as actinomycin D, cycloheximide, and dexamethasone also suppressed the interleukin-1 beta-induced prostaglandin E-2 release and the bradykinin-induced prostaglandin E-2 release in interleukin-1 beta-preheated human gingival fibroblasts. In the fibroblasts pretreated with interleukin-1 beta, Ca2+-mobilizing reagents such as ionomycin and thapsigargin mimicked the potentiating effect of bradykinin on prostaglandin E-2 release. These results suggest that interleukin-1 beta- and bradykinin-induced prostaglandin E-2 release is dependent on cyclooxygenase-2 and the potentiated effect of bradykinin in the human gingival fibroblasts primed with interleukin-1 beta is caused by Ca2+ mobilization. (C) 2000 Elsevier Science B.V. All rights reserved.