| First Author | Wang Q | Year | 2020 |
| Journal | Respir Res | Volume | 21 |
| Issue | 1 | Pages | 154 |
| PubMed ID | 32552811 | Mgi Jnum | J:291900 |
| Mgi Id | MGI:6448755 | Doi | 10.1186/s12931-020-01396-y |
| Citation | Wang Q, et al. (2020) E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR alpha7 receptor: role of nAChR alpha7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation. Respir Res 21(1):154 |
| abstractText | Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the alpha7 nicotinic acetylcholine receptor (nAChRalpha7). Adult wild-type (WT), nAChRalpha7 knockout (KO), and lung epithelial cell-specific KO (nAChRalpha7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRalpha7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRalpha7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRalpha7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRalpha7 in a sex-dependent manner. |
