Bradykinin induces a rapid cyclooxygenase-2 mRNA expression via Ca2+ mobilization in human gingival fibroblasts primed with interleukin-1 beta.
We have previously demonstrated that bradykinin potentiates prostaglandin E(2)release in human gingival fibroblasts pretreated with interleukin-1 beta (priming). In this study, we demonstrate a potentiating effect of bradykinin on cyclooxygenase-2 mRNA expression in the interleukin-1 beta-primed fibroblasts. Interleukin-1 beta (200 pg/ml) induced cyclooxygenase-2 mRNA expression, but not bradykinin (1 microM). However, bradykinin rapidly and markedly increased the cyclooxygenase-2 mRNA expression in the fibroblasts primed with interleukin-1 beta. In the primed fibroblasts, ionomycin and thapsigargin mimicked the potentiating effect of bradykinin on the cyclooxygenase-2 mRNA expression. Dexamethasone and actinomycin D completely suppressed not only the interleukin-1 beta-induced cyclooxygenase-2 mRNA expression, but also the bradykinin-induced cyclooxygenase-2 mRNA expression in the interleukin-1 beta-primed fibroblasts, although cycloheximide did not inhibit the effects of interleukin-1 beta and bradykinin. These results suggest that bradykinin-induced prostaglandin E2 synthesis is regulated at the level of the transcription of cyclooxygenase-2 mRNA via Ca2+ mobilization in the interleukin-1 beta-primed human gingival fibroblasts.
Nakao
S
S
Departments of Pharmacology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, 271-8587, Japan.
Ogata
Y
Y
Modéer
T
T
Segawa
M
M
Furuyama
S
S
Sugiya
H
H
D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000819:agonists / Q000378:metabolism*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000378:metabolism / Q000494:pharmacology; D051546:Cyclooxygenase 2; D003609:Dactinomycin / Q000378:metabolism / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005881:Gingiva / Q000166:cytology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D015759:Ionomycin / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019284:Thapsigargin / Q000378:metabolism / Q000494:pharmacology
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D003609:Dactinomycin; D015759:Ionomycin; D019284:Thapsigargin; D003907:Dexamethasone; D003513:Cycloheximide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001920:Bradykinin; D002118:Calcium