Role of Cigarette Smoke on Angiotensin-Converting Enzyme-2 Protein Membrane Expression in Bronchial Epithelial Cells Using an Air-Liquid Interface Model

Abstract

Prevalence studies of current smoking, among hospitalized COVID-19 patients, demonstrated an unexpectedly low prevalence among patients with COVID-19. The aim of the present study was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 h from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1,012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.

The effect of laboratory-verified smoking on SARS-CoV-2 infection: results from the Troina sero-epidemiological survey

“…The mechanisms by which tobacco use decreases the risk of SARS-CoV-2 infection (and increases the risk of severe prognosis in COVID-19 patients) are not fully understood. Anti-inflammatory properties mediated by α7 nicotinic acetylcholine receptors and reduction in membrane angiotensin-converting enzyme 2 (ACE-2) expression in bronchial cells—which could play a role in SARS-CoV-2 pathology—have been proposed [ 20 , 26 , 28 , 59 – 61 ]. Coronaviruses bind the ACE-2 host cell receptors through homotrimeric spike protein (i.e., S1 and S2 subunit) of their envelope, and, therefore, ACE-2 expression on bronchial tissue is a strong determinant for coronaviruses infectivity.…”

“…Coronaviruses bind the ACE-2 host cell receptors through homotrimeric spike protein (i.e., S1 and S2 subunit) of their envelope, and, therefore, ACE-2 expression on bronchial tissue is a strong determinant for coronaviruses infectivity. Some studies captured a significant decrease of membrane ACE-2 protein expression attributable to cigarette smoking [ 61 – 65 ]. Again, this effect on ACE-2 might be likely attributable to acute smoking exposure, and thus unlikely to be associated with smoking duration, as revealed by our analyses.…”

“…Obviously, even if results of a low infection rate among smokers will be confirmed in further study, smoking must not be perceived as a protective measure for COVID-19, neither encouraged nor recommended. However, the possibility for therapeutic effects of nicotine or nicotinic-cholinergic agonists on COVID-19 warrants further investigation by the research community through experimental in vitro studies and in clinical trials [ 58 , 61 , 70 ].…”

Assessment of Severe COVID-19 Outcomes Using Measures of Smoking Status and Smoking Intensity

“…Similar to prior work, we also observed a high prevalence of severe outcomes in both former smokers and current smokers. It is possible that former smokers remain at risk for continued COVID-19-related sequelae due to the potential modulatory effects of smoking on ACE2 protein expression in former and current smokers since ACE2 serves as a possible receptor by which COVID-19 may enter into epithelial cells [21,22]. Further, it is well-established that former smokers remain at risk for many illnesses, including lung cancer, CVD, and metabolic syndrome [23][24][25].…”

The association between tobacco use and COVID-19 in Qatar

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