Bradykinin potentiates prostaglandin E(2) release in the human gingival fibroblasts pretreated with interleukin-1beta via Ca(2+) mobilization.
Interleukin-1beta, 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-1beta (200 pg/ml) and bradykinin (1 microM) evoked a moderately synergistic increase in prostaglandin E(2) release in human gingival fibroblasts. However, in the human gingival fibroblasts pretreated with interleukin-1beta, bradykinin drastically enhanced prostaglandin E(2) release. NS-398, a specific inhibitor of cyclooxygenase-2, inhibited not only interleukin-1beta-induced prostaglandin E(2) release but also bradykinin-induced prostaglandin E(2) release in the human gingival fibroblasts pretreated with interleukin-1beta. Transcriptional and translational inhibitors such as actinomycin D, cycloheximide, and dexamethasone also suppressed the interleukin-1beta-induced prostaglandin E(2) release and the bradykinin-induced prostaglandin E(2) release in interleukin-1beta-pretreated human gingival fibroblasts. In the fibroblasts pretreated with interleukin-1beta, 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-1beta- 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-1beta is caused by Ca(2+) mobilization.
Nakao
S
S
Department of Pharmacology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Ogata
Y
Y
Modéer
T
T
Furuyama
S
S
Sugiya
H
H
D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D007476:Ionophores; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D003609:Dactinomycin; D015759:Ionomycin; D003513:Cycloheximide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium