title: Activation of transcription factors in human bronchial epithelial cells exposed to aqueous extracts of mainstream cigarette smoke in vitro.
abstract: This study aimed to identify the most sensitive transcription factor activated by cigarette smoke extract (CSE) and to explore cigarette smoke components that have high biological activities in a cell-base assay. Previously, we found evidence that implicated 10 different transcription factors as having a high biological activity to CSE in vitro, based on the results of a comprehensive gene expression profile. For this study, luciferase reporter assays for each transcription factor were developed in two types of human bronchial epithelial cells: NCI-H292 and BEAS-2B cells. The results demonstrated that the nuclear factor erythroid 2-related factor 2 (NRF2)/anti-oxidant response element (ARE) pathway was the most sensitive in response to CSE. Consistently, hemo oxygenase-1 (HO-1), a downstream target gene of NRF2, was effectively up-regulated in BEAS-2B cells exposed to CSE. Moreover, among 1395 cigarette smoke components, naphthoquinones including 9,10-phenaotrenquinone, quinones, benzenediols and α, β-unsaturated carbonyls, were identified as major smoke components that contribute to activating the NRF2/ARE pathway, as indicated by the ARE-reporter assay in BEAS-2B cells. Taken together, NRF2 appears to be a key molecule in the CSE-induced cellular response, and the employed methodology is helpful for the analysis of molecular and cellular effects by CSE.
authors: a R&D Group, Tobacco Business Headquarters, Scientific Product Assessment Center, Japan Tobacco Inc. , Yohohama , Japan.
authors: Takashi
authors: T
authors: Sekine
authors: a R&D Group, Tobacco Business Headquarters, Scientific Product Assessment Center, Japan Tobacco Inc. , Yohohama , Japan.
authors: Tadashi
authors: T
authors: Hirata
authors: a R&D Group, Tobacco Business Headquarters, Scientific Product Assessment Center, Japan Tobacco Inc. , Yohohama , Japan.
authors: Toshiki
authors: T
authors: Mine
authors: a R&D Group, Tobacco Business Headquarters, Scientific Product Assessment Center, Japan Tobacco Inc. , Yohohama , Japan.
authors: Yasuo
authors: Y
authors: Fukano
mesh_terms: D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045424:Complex Mixtures / Q000737:chemistry / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009499:Neutral Red; D017382:Reactive Oxygen Species; D012906:Smoke / Q000009:adverse effects* / Q000032:analysis; D062789:Tobacco Products; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014867:Water / Q000737:chemistry
chemical_list: D045424:Complex Mixtures; D017382:Reactive Oxygen Species; D012906:Smoke; D014157:Transcription Factors; D014867:Water; D009499:Neutral Red
keywords: 9,10-phenanthraquinone; BEAS-2B; NCI-H292; anti-oxidant response element; nuclear factor erythroid 2-related factor 2