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We previously reported that nuclear factor erythroid 2\u2010related 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\u2010dimensional (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\u2010cultured 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\u2010kappa B (NF\u2010\u03baB) pathways. The 3D\u2010cultured 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\u2010cultured 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\u2010\u03baB were not increased, although proinflammatory genes were upregulated. However, another inflammation\u2010related 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\u2010\u03baB.<\/jats:p>","DOI":"10.1002\/jat.3761","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T12:54:47Z","timestamp":1545396887000},"page":"717-725","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Regulation of NRF2, AP\u20101 and NF\u2010\u03baB by cigarette smoke exposure in three\u2010dimensional human bronchial epithelial cells"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4513-0768","authenticated-orcid":false,"given":"Takashi","family":"Sekine","sequence":"first","affiliation":[{"name":"Scientific Product Assessment Center R&amp;D Group, Japan Tobacco Inc.  6\u20102, Umegaoka, Aoba\u2010ku Yohohama Kanagawa 227\u20108512 Japan"},{"name":"Laboratory of Cellular Pharmacology, School of Pharmacy Aichi\u2010Gakuin University  1\u2010100 Kusumoto, Chikusa Nagoya 464\u20108650 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Hirata","sequence":"additional","affiliation":[{"name":"Scientific Product Assessment Center R&amp;D Group, Japan Tobacco Inc.  6\u20102, Umegaoka, Aoba\u2010ku Yohohama Kanagawa 227\u20108512 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinkichi","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Scientific Product Assessment Center R&amp;D Group, Japan Tobacco Inc.  6\u20102, Umegaoka, Aoba\u2010ku Yohohama Kanagawa 227\u20108512 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Ito","sequence":"additional","affiliation":[{"name":"Scientific Product Assessment Center R&amp;D Group, Japan Tobacco Inc.  6\u20102, Umegaoka, Aoba\u2010ku Yohohama Kanagawa 227\u20108512 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanae","family":"Ishimori","sequence":"additional","affiliation":[{"name":"Scientific Product Assessment Center R&amp;D Group, Japan Tobacco Inc.  6\u20102, Umegaoka, Aoba\u2010ku Yohohama Kanagawa 227\u20108512 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazushi","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Scientific Product Assessment Center R&amp;D Group, Japan Tobacco Inc.  6\u20102, Umegaoka, Aoba\u2010ku Yohohama Kanagawa 227\u20108512 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Muraki","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Pharmacology, School of Pharmacy Aichi\u2010Gakuin University  1\u2010100 Kusumoto, Chikusa Nagoya 464\u20108650 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1352.026"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2017.01.015"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41562-017-0189-z"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00390.2007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.540633"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.02.00272002"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2008.09.003"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-984-0_1"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2016.09.004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-017-0680-0"},{"key":"e_1_2_8_12_1","unstructured":"ISO. 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