PMID- 26862668 OWN - NLM STAT- MEDLINE DCOM- 20161214 LR - 20161230 IS - 1537-6524 (Electronic) IS - 1537-6516 (Linking) VI - 26 IP - 1 DP - 2016 TI - Activation of transcription factors in human bronchial epithelial cells exposed to aqueous extracts of mainstream cigarette smoke in vitro. PG - 22-31 LID - 10.3109/15376516.2015.1123788 [doi] AB - 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 alpha, beta-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. FAU - Sekine, Takashi AU - Sekine T AD - a R&D Group, Tobacco Business Headquarters, Scientific Product Assessment Center, Japan Tobacco Inc. , Yohohama , Japan. FAU - Hirata, Tadashi AU - Hirata T AD - a R&D Group, Tobacco Business Headquarters, Scientific Product Assessment Center, Japan Tobacco Inc. , Yohohama , Japan. FAU - Mine, Toshiki AU - Mine T AD - a R&D Group, Tobacco Business Headquarters, Scientific Product Assessment Center, Japan Tobacco Inc. , Yohohama , Japan. FAU - Fukano, Yasuo AU - Fukano Y AD - a R&D Group, Tobacco Business Headquarters, Scientific Product Assessment Center, Japan Tobacco Inc. , Yohohama , Japan. LA - eng PT - Journal Article DEP - 20160210 PL - England TA - Toxicol Mech Methods JT - Toxicology mechanisms and methods JID - 101134521 RN - 0 (Complex Mixtures) RN - 0 (Reactive Oxygen Species) RN - 0 (Smoke) RN - 0 (Transcription Factors) RN - 059QF0KO0R (Water) RN - 261QK3SSBH (Neutral Red) SB - IM MH - Bronchi/cytology MH - Cell Line MH - Cell Survival/drug effects MH - Complex Mixtures/chemistry/*toxicity MH - Epithelial Cells/*drug effects MH - Gene Expression Regulation/drug effects MH - Humans MH - Neutral Red MH - Reactive Oxygen Species MH - Smoke/*adverse effects/analysis MH - *Tobacco Products MH - Transcription Factors/genetics/*metabolism MH - Water/chemistry OTO - NOTNLM OT - 9,10-phenanthraquinone OT - BEAS-2B OT - NCI-H292 OT - anti-oxidant response element OT - nuclear factor erythroid 2-related factor 2 EDAT- 2016/02/11 06:00 MHDA- 2016/12/15 06:00 CRDT- 2016/02/11 06:00 PHST- 2016/02/11 06:00 [entrez] PHST- 2016/02/11 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - 10.3109/15376516.2015.1123788 [doi] PST - ppublish SO - Toxicol Mech Methods. 2016;26(1):22-31. doi: 10.3109/15376516.2015.1123788. Epub 2016 Feb 10.