AIM:
Activation of cyclooxygenase-2 (COX-2) expression by nicotine suggests a potential role for nicotine in the pathogenesis of smoking-associated periodontal disease. The aim of this study was to investigate whether chemical interactions can modulate nicotine-induced COX-2 expression in human gingival fibroblasts (HGF).
METHODS:
Cytotoxicity was investigated by using lactate dehydrogenase leakage assays and Western blotting was used to assess COX-2 expression. Furthermore, buthionine sulfoximine (BSO; an intracellular glutathione synthesis inhibitor), 2-oxothiazolidine-4-carboxylic acid (OTZ; the precursor of cysteine), and PD98059 (extracellular signal-regulated protein kinase inhibitor) were added to search for the possible regulation mechanisms of nicotine-induced COX-2 expression.
RESULTS:
Nicotine was found to elevate lactate dehydrogenase leakage in a dose-dependent manner (P<0.05). Treatment of HGF with nicotine was shown to mediate COX-2 protein expression. Pretreatment with OTZ decreased nicotine-induced COX-2 protein level by approximately 60 % (P<0.05). However, BSO enhanced nicotine-induced COX-2 protein level up to approximately 3-fold (P<0.05). Treatment of HGF with PD98059 decreased nicotine-induced COX-2 protein expression. In addition, nicotine induced extracellular signal-regulated protein kinase phosphorylation in a time-dependent manner (P<0.05).
CONCLUSION:
Nicotine may play a significant role in the pathogenesis of cigarette smoking associated-periodontitis via the activation of COX-2 which is augmented by oxidative stress and mediated by extracellular signal-regulated protein kinase signaling.
