Nicotine stimulates the expression of cyclooxygenase-2 mRNA via NFkappaB activation in human gingival fibroblasts.
Nicotine, a major component in tobacco smoke, stimulates the synthesis of prostaglandin E(2). We investigated the involvement of the transcription nuclear factor kappa B (NFkappaB) in the nicotine-induced expression of cyclooxygenase-2 (COX-2), a key enzyme for prostaglandin synthesis, in human gingival fibroblasts. Nicotine-stimulated release of prostaglandin E(2) and expression of COX-2 mRNA in a time- and dose-dependent manner. The nicotine-stimulated release of prostaglandin E(2) and expression of COX-2 mRNA and protein were inhibited by an NFkappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), by approximately 50%. Nicotine stimulation of IkappaBalpha, an inhibitor of NFkappaB degradation, was also characterized by Western blotting. Mecamylamine, a specific antagonist of the nicotinic acetylcholine receptor, failed to inhibit the effect of nicotine on prostaglandin E(2) release. When human gingival fibroblasts were incubated with [3H]-nicotine, uptake of nicotine was observed. These results suggest that nicotine is taken up by human gingival fibroblasts and that it then stimulates COX-2 expression via the activation of NFkappaB and the subsequent release of prostaglandin E(2).
Nakao
Sumi
S
Department of Oral Molecular Pharmacology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan. nakao.sumi@nihon-u.ac.jp
Ogata
Yorimasa
Y
Sugiya
Hiroshi
H
D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008464:Mecamylamine / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D016328:NF-kappa B; D018733:Nicotinic Antagonists; D012333:RNA, Messenger; D008464:Mecamylamine; D009538:Nicotine; D051546:Cyclooxygenase 2; D015232:Dinoprostone