title: Elevated expression of NF-kappaB in oral submucous fibrosis--evidence for NF-kappaB induction by safrole in human buccal mucosal fibroblasts.
abstract: Nuclear factor-kappa B (NF-kappaB) is considered to be important in many inflammatory and immune responses. The aim of this study was to compare NF-kappaB expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induction of NF-kappaB expression. Seventeen OSF and six normal buccal mucosa specimens were examined by immunohistochemistry. Primary human buccal mucosal fibroblasts (BMFs) were established and challenged with safrole, a major polyphenolic compound in the influorescence of Piper betel, by cytotoxicity and western blot assays. Furthermore, glutathione precursor N-acetyl-L-cysteine (NAC), extracellular signal-regulated protein kinase (ERK) inhibitor PD98059, cyclooxygenase-2 (COX-2) inhibitor NS-398, dexamethasone, and cyclosporin A were added to find the possible mechanism. NF-kappaB expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. Safrole was cytotoxic to BMFs in a dose-dependent manner (p<0.05). Western blot demonstrated highly elevated NF-kappaB protein expression in BMFs stimulated by safrole (p<0.05). In addition, pretreatment with pharmacological agents markedly inhibited the safrole induced-NF-kappaB expression (p<0.05). The result suggests that chewing areca quid may activate NF-kappaB expression that may be involved in the pathogenesis of OSF. NF-kappaB expression induced by safrole in fibroblasts may be mediated by ERK activation and COX-2 signal transduction pathway.
authors.affiliation: Institute of Stomatology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Ni
authors.forename: Chung-Hung
authors.initials: CH
authors.lastname: Tsai
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Yu-Chao
authors.initials: YC
authors.lastname: Chang
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D002610:Cheek; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009914:Oral Submucous Fibrosis / Q000378:metabolism*; D012451:Safrole / Q000633:toxicity*
chemical_list: D016328:NF-kappa B; D012451:Safrole