Bradykinin potentiates prostaglandin E 2 release in the human gingival fibroblasts pretreated with interleukin-1β via Ca 2+ mobilization

Abstract

Interleukin-1β, 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-1β (200 pg/ml) and bradykinin (1 μM) evoked a moderately synergistic increase in prostaglandin E 2 release in human gingival fibroblasts. However, in the human gingival fibroblasts pretreated with interleukin-1β, bradykinin drastically enhanced prostaglandin E 2 release. NS-398, a specific inhibitor of cyclooxygenase-2, inhibited not only interleukin-1β-induced prostaglandin E 2 release but also bradykinin-induced prostaglandin E 2 release in the human gingival fibroblasts pretreated with interleukin-1β. Transcriptional and translational inhibitors such as actinomycin D, cycloheximide, and dexamethasone also suppressed the interleukin-1β-induced prostaglandin E 2 release and the bradykinin-induced prostaglandin E 2 release in interleukin-1β-pretreated human gingival fibroblasts. In the fibroblasts pretreated with interleukin-1β, Ca 2+-mobilizing reagents such as ionomycin and thapsigargin mimicked the potentiating effect of bradykinin on prostaglandin E 2 release. These results suggest that interleukin-1β- 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-1β is caused by Ca 2+ mobilization.