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Inflammation Regulation via an Agonist and Antagonists of α7 Nicotinic Acetylcholine Receptors in RAW264.7 Macrophages

The α7 nicotinic acetylcholine receptor (nAChR) is widely distributed in the central and peripheral nervous systems and is closely related to a variety of nervous system diseases and inflammatory responses. The α7 nAChR subtype plays a vital role in the cholinergic anti-inflammatory pathway. In vivo...

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Autores principales: Tan, Yao, Chu, Zhaoli, Shan, Hongyu, Zhangsun, Dongting, Zhu, Xiaopeng, Luo, Sulan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955479/
https://www.ncbi.nlm.nih.gov/pubmed/35323499
http://dx.doi.org/10.3390/md20030200
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author Tan, Yao
Chu, Zhaoli
Shan, Hongyu
Zhangsun, Dongting
Zhu, Xiaopeng
Luo, Sulan
author_facet Tan, Yao
Chu, Zhaoli
Shan, Hongyu
Zhangsun, Dongting
Zhu, Xiaopeng
Luo, Sulan
author_sort Tan, Yao
collection PubMed
description The α7 nicotinic acetylcholine receptor (nAChR) is widely distributed in the central and peripheral nervous systems and is closely related to a variety of nervous system diseases and inflammatory responses. The α7 nAChR subtype plays a vital role in the cholinergic anti-inflammatory pathway. In vivo, ACh released from nerve endings stimulates α7 nAChR on macrophages to regulate the NF-κB and JAK2/STAT3 signaling pathways, thereby inhibiting the production and release of downstream proinflammatory cytokines and chemokines. Despite a considerable level of recent research on α7 nAChR-mediated immune responses, much is still unknown. In this study, we used an agonist (PNU282987) and antagonists (MLA and α-conotoxin [A10L]PnIA) of α7 nAChR as pharmacological tools to identify the molecular mechanism of the α7 nAChR-mediated cholinergic anti-inflammatory pathway in RAW264.7 mouse macrophages. The results of quantitative PCR, ELISAs, and transcriptome analysis were combined to clarify the function of α7 nAChR regulation in the inflammatory response. Our findings indicate that the agonist PNU282987 significantly reduced the expression of the IL-6 gene and protein in inflammatory macrophages to attenuate the inflammatory response, but the antagonists MLA and α-conotoxin [A10L]PnIA had the opposite effects. Neither the agonist nor antagonists of α7 nAChR changed the expression level of the α7 nAChR subunit gene; they only regulated receptor function. This study provides a reference and scientific basis for the discovery of novel α7 nAChR agonists and their anti-inflammatory applications in the future.
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spelling pubmed-89554792022-03-26 Inflammation Regulation via an Agonist and Antagonists of α7 Nicotinic Acetylcholine Receptors in RAW264.7 Macrophages Tan, Yao Chu, Zhaoli Shan, Hongyu Zhangsun, Dongting Zhu, Xiaopeng Luo, Sulan Mar Drugs Article The α7 nicotinic acetylcholine receptor (nAChR) is widely distributed in the central and peripheral nervous systems and is closely related to a variety of nervous system diseases and inflammatory responses. The α7 nAChR subtype plays a vital role in the cholinergic anti-inflammatory pathway. In vivo, ACh released from nerve endings stimulates α7 nAChR on macrophages to regulate the NF-κB and JAK2/STAT3 signaling pathways, thereby inhibiting the production and release of downstream proinflammatory cytokines and chemokines. Despite a considerable level of recent research on α7 nAChR-mediated immune responses, much is still unknown. In this study, we used an agonist (PNU282987) and antagonists (MLA and α-conotoxin [A10L]PnIA) of α7 nAChR as pharmacological tools to identify the molecular mechanism of the α7 nAChR-mediated cholinergic anti-inflammatory pathway in RAW264.7 mouse macrophages. The results of quantitative PCR, ELISAs, and transcriptome analysis were combined to clarify the function of α7 nAChR regulation in the inflammatory response. Our findings indicate that the agonist PNU282987 significantly reduced the expression of the IL-6 gene and protein in inflammatory macrophages to attenuate the inflammatory response, but the antagonists MLA and α-conotoxin [A10L]PnIA had the opposite effects. Neither the agonist nor antagonists of α7 nAChR changed the expression level of the α7 nAChR subunit gene; they only regulated receptor function. This study provides a reference and scientific basis for the discovery of novel α7 nAChR agonists and their anti-inflammatory applications in the future. MDPI 2022-03-09 /pmc/articles/PMC8955479/ /pubmed/35323499 http://dx.doi.org/10.3390/md20030200 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tan, Yao
Chu, Zhaoli
Shan, Hongyu
Zhangsun, Dongting
Zhu, Xiaopeng
Luo, Sulan
Inflammation Regulation via an Agonist and Antagonists of α7 Nicotinic Acetylcholine Receptors in RAW264.7 Macrophages
title Inflammation Regulation via an Agonist and Antagonists of α7 Nicotinic Acetylcholine Receptors in RAW264.7 Macrophages
title_full Inflammation Regulation via an Agonist and Antagonists of α7 Nicotinic Acetylcholine Receptors in RAW264.7 Macrophages
title_fullStr Inflammation Regulation via an Agonist and Antagonists of α7 Nicotinic Acetylcholine Receptors in RAW264.7 Macrophages
title_full_unstemmed Inflammation Regulation via an Agonist and Antagonists of α7 Nicotinic Acetylcholine Receptors in RAW264.7 Macrophages
title_short Inflammation Regulation via an Agonist and Antagonists of α7 Nicotinic Acetylcholine Receptors in RAW264.7 Macrophages
title_sort inflammation regulation via an agonist and antagonists of α7 nicotinic acetylcholine receptors in raw264.7 macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955479/
https://www.ncbi.nlm.nih.gov/pubmed/35323499
http://dx.doi.org/10.3390/md20030200
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