The development of an in vitro 3D model of goblet cell hyperplasia using MUC5AC expression and repeated whole aerosol exposures.

Autor: Haswell LE; British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK. Electronic address: Linsey_Haswell@bat.com., Smart D; British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK., Jaunky T; British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK., Baxter A; British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK., Santopietro S; British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK., Meredith S; British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK., Camacho OM; British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK., Breheny D; British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK., Thorne D; British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK., Gaca MD; British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK.
Jazyk: angličtina
Zdroj: Toxicology letters [Toxicol Lett] 2021 Sep 01; Vol. 347, pp. 45-57. Date of Electronic Publication: 2021 Apr 21.
DOI: 10.1016/j.toxlet.2021.04.012
Abstrakt: Goblet cell hyperplasia and overproduction of airway mucin are characteristic features of the lung epithelium of smokers and COPD patients. Tobacco heating products (THPs) are a potentially less risky alternative to combustible cigarettes, and through continued use solus THPs may reduce smoking-related disease risk. Using the MucilAir™ in vitro lung model, a 6-week feasibility study was conducted investigating the effect of repeated cigarette smoke (1R6F), THP aerosol and air exposure. Tissues were exposed to nicotine-matched whole aerosol doses 3 times/week. Endpoints assessed were dosimetry, tight-junction integrity, cilia beat frequency (CBF) and active area (AA), cytokine secretion and airway mucin MUC5AC expression. Comparison of incubator and air exposed controls indicated exposures did not have a significant effect on the transepithelial electrical resistance (TEER), CBF and AA of the tissues. Cytokine secretion indicated clear differences in secretion patterns in response to 1R6F and THP exposure. 1R6F exposure resulted in a significant decrease in the TEER and AA (p=0.000 and p=0.000, respectively), and an increase in MUC5AC positive cells (p=0.002). Repeated THP exposure did not result in a significant change in MUC5AC positive cells. This study demonstrates repeated cigarette smoke whole aerosol exposure can induce these morphological changes in vitro.
Competing Interests: Declaration of Competing Interest The authors were employees of British American Tobacco at the time of the study conduct and have no other conflicts of interest.
(Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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