The development of an in vitro 3D model of goblet cell hyperplasia using MUC5AC expression and repeated whole aerosol exposures. (1st September 2021)

• Record Type: Journal Article
• Authors: Haswell, Linsey E.; Smart, David; Jaunky, Tomasz; Baxter, Andrew; Santopietro, Simone; Meredith, Stuart; Camacho, Oscar M.; Breheny, Damien; Thorne, David; Gaca, Marianna D.
• Is Part Of: Toxicology letters. Volume 347(2021)
• Page Start: 45
• Page End: 57
• Publication Date: 2021-09-01
• Subjects: In vitro -- Lung epithelium -- Cigarette smoke -- Tobacco heating products -- MUC5AC; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2021.04.012
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Highlights importance of repeat exposure assays for modelling disease pathogenesis. Details the development and challenges of complex repeat exposure studies. First publication of repeat whole smoke exposure with increase in MUC5AC expression. MUC5AC increase is a clinically relevant endpoint for smoking related disease. Comparison of repeat tobacco heated product exposures with air and cigarette smoke. Abstract: 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 .