P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain

Yucui Jiang,1,2,&ast; Fan Ye,1,&ast; Ying Du,1 Yingxin Zong,1 Zongxiang Tang1 1School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2School of Chinese Medicine & School of Integrated Chinese and West...

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Autores principales:	Jiang Y, Ye F, Du Y, Zong Y, Tang Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	p2x7r mast cells salicylates analgesia inflammatory pain Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/9b1a6159cdaf4c608572a19465a7a50b
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spelling	oai:doaj.org-article:9b1a6159cdaf4c608572a19465a7a50b2021-12-02T16:13:41ZP2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain1178-7031https://doaj.org/article/9b1a6159cdaf4c608572a19465a7a50b2021-07-01T00:00:00Zhttps://www.dovepress.com/p2x7r-in-mast-cells-is-a-potential-target-for-salicylic-acid-and-aspir-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Yucui Jiang,1,2,&ast; Fan Ye,1,&ast; Ying Du,1 Yingxin Zong,1 Zongxiang Tang1 1School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongxiang TangSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu Province Tel +86 25 85811802Email zongxiangtang@njutcm.edu.cnBackground: Mast cells are well known for their role in inflammatory pain. P2X7 receptor (P2X7R) has attracted much attention due to its prominent role in inflammatory diseases. Salicylates are commonly used anti-inflammatory and analgesic drugs. Until now, little has been known about whether P2X7R in mast cells is involved in inflammatory pain and whether it is a potential target for salicylates.Methods: First, the expression of P2X receptors in mouse peritoneal mast cells was detected by using RT-PCR, immunofluorescence, calcium imaging and electrophysiological technique. In addition, the functions of P2X receptors, especially P2X7R, in mast cells were studied by using QPCR, ELISA and behavioral tests. Furthermore, P2X7R was used as a target to screen for some anti-inflammatory monomers that could inhibit its activity. At last, the effect of salicylic acid (SA) and aspirin (ASA) on the activity of P2X7R was studied by using calcium imaging, electrophysiological technique, ELISA, real-time PCR, behavioral tests, immunofluorescence and molecular docking.Results: We found that P2X1, P2X3, P2X4 and P2X7 receptors were expressed in mouse peritoneal mast cells. The functions of different P2X receptors were various. Activation of P2X7R in mouse mast cells induced the release of inflammatory mediators, such as histamine, IL-1β, and CCL3. In addition, inflammation pain induced by high concentrations of ATP could be alleviated by P2X7R blockers or mast cell defects. Interestingly, SA or ASA could reduce high concentrations of ATP-induced inward current, P2X7R upregulation, mediators release, and inflammatory pain. SA or ASA also inhibited the inward current evoked by P2X7R agonist, BZATP. Molecular docking showed that SA or ASA had affinity for the cytoplasmic GDP-binding region of P2X7R.Conclusion: P2X7R in mast cells was involved in inflammation pain by releasing inflammatory mediators, and P2X7R might be a potential target for SA and ASA analgesia.Keywords: P2X7R, mast cells, salicylates, analgesia, inflammatory painJiang YYe FDu YZong YTang ZDove Medical Pressarticlep2x7rmast cellssalicylatesanalgesiainflammatory painPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 2913-2931 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	p2x7r mast cells salicylates analgesia inflammatory pain Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	p2x7r mast cells salicylates analgesia inflammatory pain Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Jiang Y Ye F Du Y Zong Y Tang Z P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain
description	Yucui Jiang,1,2,&ast; Fan Ye,1,&ast; Ying Du,1 Yingxin Zong,1 Zongxiang Tang1 1School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongxiang TangSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu Province Tel +86 25 85811802Email zongxiangtang@njutcm.edu.cnBackground: Mast cells are well known for their role in inflammatory pain. P2X7 receptor (P2X7R) has attracted much attention due to its prominent role in inflammatory diseases. Salicylates are commonly used anti-inflammatory and analgesic drugs. Until now, little has been known about whether P2X7R in mast cells is involved in inflammatory pain and whether it is a potential target for salicylates.Methods: First, the expression of P2X receptors in mouse peritoneal mast cells was detected by using RT-PCR, immunofluorescence, calcium imaging and electrophysiological technique. In addition, the functions of P2X receptors, especially P2X7R, in mast cells were studied by using QPCR, ELISA and behavioral tests. Furthermore, P2X7R was used as a target to screen for some anti-inflammatory monomers that could inhibit its activity. At last, the effect of salicylic acid (SA) and aspirin (ASA) on the activity of P2X7R was studied by using calcium imaging, electrophysiological technique, ELISA, real-time PCR, behavioral tests, immunofluorescence and molecular docking.Results: We found that P2X1, P2X3, P2X4 and P2X7 receptors were expressed in mouse peritoneal mast cells. The functions of different P2X receptors were various. Activation of P2X7R in mouse mast cells induced the release of inflammatory mediators, such as histamine, IL-1β, and CCL3. In addition, inflammation pain induced by high concentrations of ATP could be alleviated by P2X7R blockers or mast cell defects. Interestingly, SA or ASA could reduce high concentrations of ATP-induced inward current, P2X7R upregulation, mediators release, and inflammatory pain. SA or ASA also inhibited the inward current evoked by P2X7R agonist, BZATP. Molecular docking showed that SA or ASA had affinity for the cytoplasmic GDP-binding region of P2X7R.Conclusion: P2X7R in mast cells was involved in inflammation pain by releasing inflammatory mediators, and P2X7R might be a potential target for SA and ASA analgesia.Keywords: P2X7R, mast cells, salicylates, analgesia, inflammatory pain
format	article
author	Jiang Y Ye F Du Y Zong Y Tang Z
author_facet	Jiang Y Ye F Du Y Zong Y Tang Z
author_sort	Jiang Y
title	P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain
title_short	P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain
title_full	P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain
title_fullStr	P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain
title_full_unstemmed	P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain
title_sort	p2x7r in mast cells is a potential target for salicylic acid and aspirin in treatment of inflammatory pain
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/9b1a6159cdaf4c608572a19465a7a50b
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P2X7R in Mast Cells is a Potential Target for Salicylic Acid and Aspirin in Treatment of Inflammatory Pain

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