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ImmunoAnalysis. 2021;1: 10.
doi: 10.34172/ia.2021.10
  Abstract View: 533
  PDF Download: 203

Original Research

Nicotinic Acetylcholine Receptor Subunit Alpha-7 Mediates PD-L1 and CTLA-4 Expression in HepG2 Cells

Mina Afrashteh Nour 1, 2 ORCID logo, Fatemeh Kheradmand 2 ORCID logo, Yousef Rasmi 2 ORCID logo, Zahra Asadzadeh 1 ORCID logo, Mohammad Amin Doustvandi 1 ORCID logo, Mahdi Jafarlou 1 ORCID logo, Khalil Hajiasgharzadeh 1, 3* ORCID logo, Behzad Baradaran 1* ORCID logo

1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Clinical Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
3 Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
*Corresponding Authors: Email: hajiasgharzadeh@tbzmed.ac.ir; Email: baradaranb@tbzmed.ac.ir

Abstract

Background: The liver is the largest solid organ in the body and has several unique immunological roles. The alpha7 subtype of nicotinic acetylcholine receptor (α7nAChR) is expressed in the liver and has different immunoregulatory effects. Programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two major checkpoints that act as a negative regulator of the immune system. In this study, we examined the effects of activation (with nicotine) and inhibition (with specific siRNA) of α7nAChR on the PD-L1 and CTLA-4 genes expression.

Methods: Human hepatocellular carcinoma (HepG2) cell line was used to investigate the effects of treatment with low dose (1 μM) and high dose (10 μM) of nicotine on the PD-L1 and CTLA-4 expression. In addition to this, the effects of treatment with 100 nM concentration of specific siRNA targeting α7nAChR (α7-siRNA) were examined using quantitative real-time PCR.

Results: Compared to untreated cells, the HepG2 cells treated with nicotine exhibited significant dose-dependent decreases in PD-L1 expression. Furthermore, nicotine has a biphasic effect on the CTLA-4 expression and decreased its expression in 10 μM concentration. The qRT-PCR revealed that α7-siRNA significantly reduced the mRNA levels of α7nAChR (P < 0.01). Also, compared to control cells, α7-siRNA treated cells exhibited significant increases in both PD-L1 and CTLA-4 expression.

Conclusion: These experiments determined that nicotine treatment leads to decreases in PD-L1 and CTLA-4 expression. These effects are reversed by treatment with α7-siRNA, which indicates the involvement of α7nAChR related mechanisms in these processes.

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Submitted: 30 Nov 2021
Revision: 18 Dec 2021
Accepted: 20 Dec 2021
ePublished: 28 Dec 2021
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