Late Breaking Abstract-ACE2 Overexpression Modulates Nicotine Receptors In Cell Type Specific Manner: Possible Relevance In Covid-19

The SARS-CoV-2 uses the host cell receptor ACE2 to infect humans. Increased ACE2 levels found in patients with metabolic disorders, obesity and hypertension correlate to an increased risk for SARS-CoV-2 infection. Nicotinic receptors (nAChRs) are involved in the modulation of the inflammatory and immunological responses through the cholinergic system. Based on this, we hypothesize that ACE2 overexpression may modulate nAChRs on lung and kidney cells and this can be relevant for understanding the mechanisms involved in the COVID-19 physiopathology. Aim: To evaluate if ACE2 overexpression modulates the expression of α7-nAChR) and α3-nAChR in three human cells lines derived from bronchial epithelial, lung epithelial, and embryonic kidney. Methods: The overexpression of ACE2 was accomplished by transfecting BEAS-2B, A549, and HEK293 cells with pCEP-ACE2-myc and selecting with hygromycin (125ng/µL) for 15 days. α7nAChR and α3nAChR gene expression was quantified by RT-qPCR (n=3). Results: In BEAS-2B, no significant difference was found in the expression of α3nAChR and α7nAChR, however, in A549, the long-term overexpression of ACE2 significantly increased the expression of α7nAChR (4.8± 0.2) (P<0.001), but did not affect α3nAChR (1.9±0.5) levels compared to control (α7nAChR: 0.8±0.1; α3nAChR: 0.9±0.1). In HEK293 cells, the overexpression of ACE2 diminished the α7nAChR (0.4±0.1) and increased the α3nAChR (2.1±0.2) compared to control (α7nAChR: 1.1±0.1; α3nAChR: 1.1±0.1, P≤0.01). Conclusion: The levels of ACE2 selectively modulates the expression of nAChRs in different cells lineages. This can be relevant for further investigation of the potential roles of nAChR in COVID-19.