Nicotinic Acetylcholine Receptor Subunit α7 Mediates Cigarette Smoke-Induced PD-L1 Expression in Human Bronchial Epithelial Cells

Tobacco smoking is the top risk factor for lung cancer development. Nicotine in cigarettes can induce addiction, and its derivatives become potent carcinogens after metabolic activation and activate oncogenic signaling in lung epithelial cells through their expressed nicotinic acetylcholine receptor...

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Autores principales:	Hoi-Hin Kwok, Boning Gao, Koon-Ho Chan, Mary Sau-Man Ip, John Dorrance Minna, David Chi-Leung Lam
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	lung cancer cigarette smoke PD-L1 <i>CHRNA7</i> bronchial epithelial cells Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/6f3d049dbfe547e492a1d6aef1a24d41
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spelling	oai:doaj.org-article:6f3d049dbfe547e492a1d6aef1a24d412021-11-11T15:28:46ZNicotinic Acetylcholine Receptor Subunit α7 Mediates Cigarette Smoke-Induced PD-L1 Expression in Human Bronchial Epithelial Cells10.3390/cancers132153452072-6694https://doaj.org/article/6f3d049dbfe547e492a1d6aef1a24d412021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5345https://doaj.org/toc/2072-6694Tobacco smoking is the top risk factor for lung cancer development. Nicotine in cigarettes can induce addiction, and its derivatives become potent carcinogens after metabolic activation and activate oncogenic signaling in lung epithelial cells through their expressed nicotinic acetylcholine receptors (nAChRs). However, the effects of smoking on the tumor immune microenvironment are under investigation. In the current study, we investigated whether nicotine activation of nicotinic acetylcholine receptor subunit α7 (nAChRα7, <i>CHRNA7</i>) would induce PD-L1 expression in lung epithelial cells. The expression levels of nAChRα7 and PD-L1 in eight human bronchial epithelial cell (HBEC) lines were measured after treatment with cigarette smoke extract (CSE) or nicotine derivatives. The results showed that PD-L1 expression levels increased in HBECs after exposure to CSE or nicotine derivatives. This induction of PD-L1 expression could be diminished by treatment with <i>CHRNA7</i> small-interfering RNA, and the relevant signaling was mediated via STAT3 phosphorylation and NRF2 expression. In summary, this study demonstrated that the well-known nicotine derivative-activated nAChRα7 could induce STAT3/NRF2 pathways and subsequently promote PD-L1 expression in normal lung epithelial cells. This information provides mechanistic insight into cigarette smoke-induced immune evasion in lung epithelial cells.Hoi-Hin KwokBoning GaoKoon-Ho ChanMary Sau-Man IpJohn Dorrance MinnaDavid Chi-Leung LamMDPI AGarticlelung cancercigarette smokePD-L1<i>CHRNA7</i>bronchial epithelial cellsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5345, p 5345 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lung cancer cigarette smoke PD-L1 <i>CHRNA7</i> bronchial epithelial cells Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	lung cancer cigarette smoke PD-L1 <i>CHRNA7</i> bronchial epithelial cells Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hoi-Hin Kwok Boning Gao Koon-Ho Chan Mary Sau-Man Ip John Dorrance Minna David Chi-Leung Lam Nicotinic Acetylcholine Receptor Subunit α7 Mediates Cigarette Smoke-Induced PD-L1 Expression in Human Bronchial Epithelial Cells
description	Tobacco smoking is the top risk factor for lung cancer development. Nicotine in cigarettes can induce addiction, and its derivatives become potent carcinogens after metabolic activation and activate oncogenic signaling in lung epithelial cells through their expressed nicotinic acetylcholine receptors (nAChRs). However, the effects of smoking on the tumor immune microenvironment are under investigation. In the current study, we investigated whether nicotine activation of nicotinic acetylcholine receptor subunit α7 (nAChRα7, <i>CHRNA7</i>) would induce PD-L1 expression in lung epithelial cells. The expression levels of nAChRα7 and PD-L1 in eight human bronchial epithelial cell (HBEC) lines were measured after treatment with cigarette smoke extract (CSE) or nicotine derivatives. The results showed that PD-L1 expression levels increased in HBECs after exposure to CSE or nicotine derivatives. This induction of PD-L1 expression could be diminished by treatment with <i>CHRNA7</i> small-interfering RNA, and the relevant signaling was mediated via STAT3 phosphorylation and NRF2 expression. In summary, this study demonstrated that the well-known nicotine derivative-activated nAChRα7 could induce STAT3/NRF2 pathways and subsequently promote PD-L1 expression in normal lung epithelial cells. This information provides mechanistic insight into cigarette smoke-induced immune evasion in lung epithelial cells.
format	article
author	Hoi-Hin Kwok Boning Gao Koon-Ho Chan Mary Sau-Man Ip John Dorrance Minna David Chi-Leung Lam
author_facet	Hoi-Hin Kwok Boning Gao Koon-Ho Chan Mary Sau-Man Ip John Dorrance Minna David Chi-Leung Lam
author_sort	Hoi-Hin Kwok
title	Nicotinic Acetylcholine Receptor Subunit α7 Mediates Cigarette Smoke-Induced PD-L1 Expression in Human Bronchial Epithelial Cells
title_short	Nicotinic Acetylcholine Receptor Subunit α7 Mediates Cigarette Smoke-Induced PD-L1 Expression in Human Bronchial Epithelial Cells
title_full	Nicotinic Acetylcholine Receptor Subunit α7 Mediates Cigarette Smoke-Induced PD-L1 Expression in Human Bronchial Epithelial Cells
title_fullStr	Nicotinic Acetylcholine Receptor Subunit α7 Mediates Cigarette Smoke-Induced PD-L1 Expression in Human Bronchial Epithelial Cells
title_full_unstemmed	Nicotinic Acetylcholine Receptor Subunit α7 Mediates Cigarette Smoke-Induced PD-L1 Expression in Human Bronchial Epithelial Cells
title_sort	nicotinic acetylcholine receptor subunit α7 mediates cigarette smoke-induced pd-l1 expression in human bronchial epithelial cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6f3d049dbfe547e492a1d6aef1a24d41
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Nicotinic Acetylcholine Receptor Subunit α7 Mediates Cigarette Smoke-Induced PD-L1 Expression in Human Bronchial Epithelial Cells

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