PMID- 30575053 OWN - NLM STAT- MEDLINE DCOM- 20200817 LR - 20231213 IS - 1099-1263 (Electronic) IS - 0260-437X (Linking) VI - 39 IP - 5 DP - 2019 May TI - Regulation of NRF2, AP-1 and NF-kappaB by cigarette smoke exposure in three-dimensional human bronchial epithelial cells. PG - 717-725 LID - 10.1002/jat.3761 [doi] AB - Cigarette smoke (CS) is a complex mixture of chemicals and interacts with various physiological processes. We previously reported that nuclear factor erythroid 2-related factor 2 (NRF2) was the most sensitive transcription factor to aqueous CS extract (AqCSE) exposure in monolayer cultured human bronchial epithelial cell lines. Recently, in vitro three-dimensional (3D) culture models have been used to supplement pharmacological and toxicological assessments. Bronchial epithelium models in particular are useful for the evaluation of substances that directly contact the respiratory tract, such as CS. In the present study, we used 3D-cultured human bronchial epithelial cells (HBECs) to assess activation of transcription factors and relevant gene expression in response to AqCSE, primarily focusing on NRF2 and nuclear factor-kappa B (NF-kappaB) pathways. The 3D-cultured HBECs exposed to AqCSE showed expression of NRF2 and its nuclear translocation in addition to upregulation of genes related to oxidative stress. Our results suggest that the NRF2 pathway was the dominant pathway when 3D-cultured HBECs were exposed to AqCSE at a low dose, supporting our previous findings that NRF2 was the most sensitive transcription factor in response to AqCSE. Expression and nuclear translocation of NF-kappaB were not increased, although proinflammatory genes were upregulated. However, another inflammation-related transcription factor, activation protein 1, was induced by AqCSE. Gene classification analysis suggested that induction of the inflammatory response by AqCSE was dependent on NRF2 and activation protein 1 rather than NF-kappaB. CI - (c) 2018 John Wiley & Sons, Ltd. FAU - Sekine, Takashi AU - Sekine T AUID- ORCID: 0000-0003-4513-0768 AD - Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yohohama, Kanagawa, 227-8512, Japan. AD - Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya, 464-8650, Japan. FAU - Hirata, Tadashi AU - Hirata T AD - Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yohohama, Kanagawa, 227-8512, Japan. FAU - Ishikawa, Shinkichi AU - Ishikawa S AD - Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yohohama, Kanagawa, 227-8512, Japan. FAU - Ito, Shigeaki AU - Ito S AD - Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yohohama, Kanagawa, 227-8512, Japan. FAU - Ishimori, Kanae AU - Ishimori K AD - Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yohohama, Kanagawa, 227-8512, Japan. FAU - Matsumura, Kazushi AU - Matsumura K AD - Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yohohama, Kanagawa, 227-8512, Japan. FAU - Muraki, Katsuhiko AU - Muraki K AD - Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya, 464-8650, Japan. LA - eng PT - Journal Article DEP - 20181221 PL - England TA - J Appl Toxicol JT - Journal of applied toxicology : JAT JID - 8109495 RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (NFE2L2 protein, human) RN - 0 (Smoke) RN - 0 (Transcription Factor AP-1) SB - IM MH - Adult MH - Bronchi/*drug effects/metabolism MH - Cell Survival/drug effects MH - Cells, Cultured MH - Epithelial Cells/*drug effects/metabolism MH - Gene Expression Regulation/drug effects MH - Humans MH - Male MH - NF-E2-Related Factor 2/genetics/*metabolism MH - NF-kappa B/genetics/*metabolism MH - Oxidative Stress/drug effects MH - Smoke/*adverse effects MH - Smoking/adverse effects MH - Nicotiana/*toxicity MH - Transcription Factor AP-1/genetics/*metabolism OTO - NOTNLM OT - activator protein 1 OT - cigarette smoke OT - human bronchial epithelial cells OT - inflammation OT - nuclear factor erythroid 2-related factor 2 OT - nuclear factor-kappa B OT - oxidative stress OT - three-dimensional culture EDAT- 2018/12/24 06:00 MHDA- 2020/08/18 06:00 CRDT- 2018/12/22 06:00 PHST- 2018/10/03 00:00 [received] PHST- 2018/11/07 00:00 [revised] PHST- 2018/11/08 00:00 [accepted] PHST- 2018/12/24 06:00 [pubmed] PHST- 2020/08/18 06:00 [medline] PHST- 2018/12/22 06:00 [entrez] AID - 10.1002/jat.3761 [doi] PST - ppublish SO - J Appl Toxicol. 2019 May;39(5):717-725. doi: 10.1002/jat.3761. Epub 2018 Dec 21.