Effects of repeated cigarette smoke extract exposure over one month on human bronchial epithelial organotypic culture

Cigarette smoke is a known risk factor for inflammatory diseases in the respiratory tract, and inflammatory exacerbation is considered pivotal to the pathogenesis of these diseases. Here, we performed two repeated exposure studies in which we exposed human bronchial epithelial tissues in an organoty...

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Main Authors: Shigeaki Ito, Kanae Ishimori, Shinkichi Ishikawa
Format: Article
Language:English
Published: Elsevier 2018-01-01
Series:Toxicology Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2214750018303755
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author Shigeaki Ito
Kanae Ishimori
Shinkichi Ishikawa
author_facet Shigeaki Ito
Kanae Ishimori
Shinkichi Ishikawa
author_sort Shigeaki Ito
collection DOAJ
description Cigarette smoke is a known risk factor for inflammatory diseases in the respiratory tract, and inflammatory exacerbation is considered pivotal to the pathogenesis of these diseases. Here, we performed two repeated exposure studies in which we exposed human bronchial epithelial tissues in an organotypic culture model to cigarette smoke extract (CSE); the first study was conducted over a four-day period to determine the suitable dose range for the extended exposure period, and the second was a one-month exposure study to elucidate the exposure-by-exposure effects in bronchial tissues. We focused on matrix metalloproteinase (MMP)-9 and -1/3 and the inflammatory cytokines interleukin (IL)-8 and growth factor related oncogene to evaluate the transition into an inflammatory state. Even at CSE doses with no or low toxicity for a single exposure, the repetition of exposure induced cumulative effects on both the inflammatory responses, specifically the IL-8 and MMPs levels, and tissue morphology. Interestingly, untreated controls initially had relatively high baseline levels of these secreted proteins; these levels gradually declined, after which they showed periodic level changes, suggesting an acclimation period may be needed for this system. These results demonstrate the usability of this system for the elucidation of sub-chronic effects in vitro. Keywords: Cigarette smoke extract, Repeated exposure, Organotypic culture
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spelling doaj.art-bdea9b8c96c14bbf9065b0cb83bcc1f62022-12-22T00:47:14ZengElsevierToxicology Reports2214-75002018-01-015864870Effects of repeated cigarette smoke extract exposure over one month on human bronchial epithelial organotypic cultureShigeaki Ito0Kanae Ishimori1Shinkichi Ishikawa2Corresponding author at: Scientific Product Assessment Center, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yokohama, Kanagawa, 227-8512, Japan.; Scientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yokohama, Kanagawa, 227-8512, JapanScientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yokohama, Kanagawa, 227-8512, JapanScientific Product Assessment Center, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yokohama, Kanagawa, 227-8512, JapanCigarette smoke is a known risk factor for inflammatory diseases in the respiratory tract, and inflammatory exacerbation is considered pivotal to the pathogenesis of these diseases. Here, we performed two repeated exposure studies in which we exposed human bronchial epithelial tissues in an organotypic culture model to cigarette smoke extract (CSE); the first study was conducted over a four-day period to determine the suitable dose range for the extended exposure period, and the second was a one-month exposure study to elucidate the exposure-by-exposure effects in bronchial tissues. We focused on matrix metalloproteinase (MMP)-9 and -1/3 and the inflammatory cytokines interleukin (IL)-8 and growth factor related oncogene to evaluate the transition into an inflammatory state. Even at CSE doses with no or low toxicity for a single exposure, the repetition of exposure induced cumulative effects on both the inflammatory responses, specifically the IL-8 and MMPs levels, and tissue morphology. Interestingly, untreated controls initially had relatively high baseline levels of these secreted proteins; these levels gradually declined, after which they showed periodic level changes, suggesting an acclimation period may be needed for this system. These results demonstrate the usability of this system for the elucidation of sub-chronic effects in vitro. Keywords: Cigarette smoke extract, Repeated exposure, Organotypic culturehttp://www.sciencedirect.com/science/article/pii/S2214750018303755
spellingShingle Shigeaki Ito
Kanae Ishimori
Shinkichi Ishikawa
Effects of repeated cigarette smoke extract exposure over one month on human bronchial epithelial organotypic culture
Toxicology Reports
title Effects of repeated cigarette smoke extract exposure over one month on human bronchial epithelial organotypic culture
title_full Effects of repeated cigarette smoke extract exposure over one month on human bronchial epithelial organotypic culture
title_fullStr Effects of repeated cigarette smoke extract exposure over one month on human bronchial epithelial organotypic culture
title_full_unstemmed Effects of repeated cigarette smoke extract exposure over one month on human bronchial epithelial organotypic culture
title_short Effects of repeated cigarette smoke extract exposure over one month on human bronchial epithelial organotypic culture
title_sort effects of repeated cigarette smoke extract exposure over one month on human bronchial epithelial organotypic culture
url http://www.sciencedirect.com/science/article/pii/S2214750018303755
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AT kanaeishimori effectsofrepeatedcigarettesmokeextractexposureoveronemonthonhumanbronchialepithelialorganotypicculture
AT shinkichiishikawa effectsofrepeatedcigarettesmokeextractexposureoveronemonthonhumanbronchialepithelialorganotypicculture