Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV-2 Infection Severity

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 1; p. 101
• Main Authors: Lupacchini, Leonardo, Maggi, Fabrizio, Tomino, Carlo, De Dominicis, Chiara, Mollinari, Cristiana, Fini, Massimo, Bonassi, Stefano, Merlo, Daniela, Russo, Patrizia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.12.2020; MDPI
• Subjects: ACE2; Acetylcholine receptors (nicotinic); alpha7 Nicotinic Acetylcholine Receptor - metabolism; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; ATP; Binding sites; Calcium (intracellular); Calcium ions; Cell growth; Cell Line; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; Cloning; Coronaviruses; COVID-19; COVID-19 - pathology; COVID-19 - virology; EMT; Enzyme-linked immunosorbent assay; Epidemiology; Epidermal growth factor receptors; Epithelial Cells - drug effects; Epithelial Cells - virology; Gene expression; Homeostasis; Humans; Hypotheses; Infections; Ligands; Mimicry; mitochondrial dysfunction; mRNA; nAChR; Nicotine; Nicotine - adverse effects; Overexpression; p53 Protein; Phenotypes; Proteins; Receptors, Nicotinic - metabolism; Respiratory System - drug effects; Respiratory System - virology; SARS-CoV-2; SARS-CoV-2 - pathogenicity; Senescence; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Signal Transduction - drug effects; Smoking - adverse effects; Smoking cessation; Substrates; Tobacco; Vaping; Vascular endothelial growth factor; Viral diseases; Western blotting; SARS-CoV-2; nicotine; mitochondrial dysfunction; cell proliferation; EMT; nAChR
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26010101

(1) Background: Nicotine is implicated in the SARS-COV-2 infection through activation of the α7-nAChR and over-expression of ACE2. Our objective was to clarify the role of nicotine in SARS-CoV-2 infection exploring its molecular and cellular activity. (2) Methods: HBEpC or si-mRNA-α7-HBEpC were treated for 1 h, 48 h or continuously with 10 M nicotine, a concentration mimicking human exposure to a cigarette. Cell viability and proliferation were evaluated by trypan blue dye exclusion and cell counting, migration by cell migration assay, senescence by SA-β-Gal activity, and anchorage-independent growth by cloning in soft agar. Expression of Ki67, p53/phospho-p53, VEGF, EGFR/pEGFR, phospho-p38, intracellular Ca , ATP and EMT were evaluated by ELISA and/or Western blotting. (3) Results: nicotine induced through α7-nAChR (i) increase in cell viability, (ii) cell proliferation, (iii) Ki67 over-expression, (iv) phospho-p38 up-regulation, (v) EGFR/pEGFR over-expression, (vi) increase in basal Ca concentration, (vii) reduction of ATP production, (viii) decreased level of p53/phospho-p53, (ix) delayed senescence, (x) VEGF increase, (xi) EMT and consequent (xii) enhanced migration, and (xiii) ability to grow independently of the substrate. (4) Conclusions: Based on our results and on evidence showing that nicotine potentiates viral infection, it is likely that nicotine is involved in SARS-CoV-2 infection and severity.