Regional heterogeneity in response of airway epithelial cells to cigarette smoke

Abstract

BackgroundCigarette smoke (CS) exposure causes an abnormal inflammatory response, which can result in chronic obstructive pulmonary disease (COPD). Previous studies show that this disorder predominantly occurs in peripheral or small-airway areas, whereas the same condition has not been identified in the larger airways during the course of COPD. However, the different biochemical and genetic alterations occurring in response to CS exposure among airway epithelial cells from different sites in the lungs have not been fully investigated.MethodsHuman small airway epithelial cells (SAECs) and normal human bronchial epithelial cells (NHBEs) were exposed to CS extract (CSE), and microarray analysis was used to determine gene- and protein-expression profiles and identify alterations following CSE exposure in both cell types. An in vivo smoking experiment was also performed to confirm differential responses to CS between sites in the lung.ResultsMicroarray analysis of SAECs and NHBEs following 24 h of CSE exposure showed that inflammatory related pathways and terms, including the tumor necrosis factor-signaling pathway, were overrepresented, especially in SAECs. Clustering analysis highlighted prostaglandin-endoperoxide synthase-2 [also known as cyclooxygenase (COX)-2] as a gene specifically upregulated in SAECs, with COX-2 mRNA and protein expression significantly elevated by CSE exposure in SAECs (3.1- and 3.1-fold, respectively), but not in NHBEs. Furthermore, time-course analysis of COX-2 expression revealed earlier increases in SAECs compared with NHBEs following CS exposure. Short-term exposure of mouse lungs to CS was found to predominantly induce COX-2 expression in the small airway.ConclusionsThe small airway is more susceptible to CSE than the large airway and could be the initial site of development of CS-related respiratory diseases, such as COPD.Electronic supplementary materialThe online version of this article (10.1186/s12890-018-0715-4) contains supplementary material, which is available to authorized users.

Characterisation of Aspergillus fumigatus Endocytic Trafficking within Airway Epithelial Cells Using High-Resolution Automated Quantitative Confocal Microscopy

“…Direct comparisons of Aspergillus fate in A549 and 16HBE cell lines have not been previously addressed (for review [70]), despite differential activation with lipopolysaccharide [46], Fusobacterium [71], glucocorticoids [72] and cigarette smoke [73] exposure. Overall, 16HBE cells were able to take up the A. fumigatus strains ∆pksp and ∆rodA more efficiently than A549, which may be linked with increased expression of mucus on the epithelia [74].…”

Tobacco Smoke and Inhaled Drugs Alter Expression and Activity of Multidrug Resistance-Associated Protein-1 (MRP1) in Human Distal Lung Epithelial Cells in vitro

“…Moreover, the pulmonary clearance of inhaled [ 99 m Tc] methoxyisobutyl isonitrile ([ 99 m Tc] sestamibi), a radiolabeled MRP1 substrate, has been recorded to decrease in smokers and the decrement was attributed to modulation in MRP1 activity and expression profile ( Mohan et al, 2019 ). The distal lung epithelium has been reported to be the initial site of development of tobacco smoke-induced diseases such as COPD ( Baskoro et al, 2018 ). Thus, we investigated the potential impact of CSE on MRP1 activity and/or abundance in human AT1-like and NCI-H441 cells.…”

Cigarette Smoke Condensate Exposure Changes RNA Content of Extracellular Vesicles Released from Small Airway Epithelial Cells

“…The different type of airway epithelia cells and cigarette smoke sources could be responsible for the differences in our results. For example, Baskoro demonstrated that SAE cells exhibit a different proinflammatory response to cigarette smoke exposure compared to HBEs [49].…”