S. Nakao et al., Bradykinin potentiates prostaglandin E-2 release in the human gingival fibroblasts pretreated with interleukin-1 beta via Ca2+ mobilization, EUR J PHARM, 395(3), 2000, pp. 247-253
Interleukin-1 beta, a proinflammatory cytokine, causes a slow increase in p
rostaglandin E-2 release. On the other hand, bradykinin, a chemical mediato
r for inflammation, induces a rapid prostaglandin E-2 release. Simultaneous
stimulation with interleukin-1 beta (200 pg/ml) and bradykinin (1 mu M) ev
oked a moderately synergistic increase in prostaglandin E-2 release in huma
n gingival fibroblasts. However, in the human gingival fibroblasts pretreat
ed 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 bradyki
nin-induced prostaglandin E-2 release in the human gingival fibroblasts pre
treated with interleukin-1 beta. Transcriptional and translational inhibito
rs 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 gi
ngival fibroblasts. In the fibroblasts pretreated with interleukin-1 beta,
Ca2+-mobilizing reagents such as ionomycin and thapsigargin mimicked the po
tentiating 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 brad
ykinin in the human gingival fibroblasts primed with interleukin-1 beta is
caused by Ca2+ mobilization. (C) 2000 Elsevier Science B.V. All rights rese
rved.