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Rhein antagonizes P2X(7) receptor in rat peritoneal macrophages
P2X(7) receptor plays important roles in inflammation and immunity, and thereby it serves as a potential therapeutic target for inflammatory diseases. Rhein, an anthraquinone derivative, exhibits significant anti-inflammatory and immunosuppressive activities in therapy. However, the underlying mecha...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564849/ https://www.ncbi.nlm.nih.gov/pubmed/26354875 http://dx.doi.org/10.1038/srep14012 |
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author | Hu, Fen Xing, Fulin Zhu, Ge Xu, Guangxue Li, Cunbo Qu, Junle Lee, Imshik Pan, Leiting |
author_facet | Hu, Fen Xing, Fulin Zhu, Ge Xu, Guangxue Li, Cunbo Qu, Junle Lee, Imshik Pan, Leiting |
author_sort | Hu, Fen |
collection | PubMed |
description | P2X(7) receptor plays important roles in inflammation and immunity, and thereby it serves as a potential therapeutic target for inflammatory diseases. Rhein, an anthraquinone derivative, exhibits significant anti-inflammatory and immunosuppressive activities in therapy. However, the underlying mechanisms are largely unclear. Here, we aimed to investigate the effects of rhein on P2X(7) receptor-mediated responses in vitro. In HEK293 cells expressing rat P2X(7) receptor, we first found that rhein concentration-dependently blocked ATP-induced cytosolic calcium concentration ([Ca(2+)](c)) elevation and pore formation of the plasma membrane, two hallmarks of the P2X(7) receptor activation. These two inhibitory effects of rhein were also observed in rat peritoneal macrophages. Furthermore, rhein counteracted macrophage phagocytosis attenuation and suppressed reactive oxygen species (ROS) production triggered by ATP/BzATP. Meanwhile, rhein reduced ATP/BzATP-induced IL-1β release in lipopolysaccharide-activated macrophages. Prolonged application of ATP caused macrophage apoptosis, while the presence of rhein suppressed this cell cytotoxicity. Such ATP/BzATP-induced cellular reactions were also inhibited by a well-known rat P2X(7) receptor antagonist, brilliant blue G, in a similar way to rhein. Together, our results demonstrate that rhein inhibit ATP/BzATP-induced [Ca(2+)](c) increase, pore formation, ROS production, phagocytosis attenuation, IL-1β release and cell apoptosis by antagonizing the P2X(7) receptor in rat peritoneal macrophages. |
format | Online Article Text |
id | pubmed-4564849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45648492015-09-15 Rhein antagonizes P2X(7) receptor in rat peritoneal macrophages Hu, Fen Xing, Fulin Zhu, Ge Xu, Guangxue Li, Cunbo Qu, Junle Lee, Imshik Pan, Leiting Sci Rep Article P2X(7) receptor plays important roles in inflammation and immunity, and thereby it serves as a potential therapeutic target for inflammatory diseases. Rhein, an anthraquinone derivative, exhibits significant anti-inflammatory and immunosuppressive activities in therapy. However, the underlying mechanisms are largely unclear. Here, we aimed to investigate the effects of rhein on P2X(7) receptor-mediated responses in vitro. In HEK293 cells expressing rat P2X(7) receptor, we first found that rhein concentration-dependently blocked ATP-induced cytosolic calcium concentration ([Ca(2+)](c)) elevation and pore formation of the plasma membrane, two hallmarks of the P2X(7) receptor activation. These two inhibitory effects of rhein were also observed in rat peritoneal macrophages. Furthermore, rhein counteracted macrophage phagocytosis attenuation and suppressed reactive oxygen species (ROS) production triggered by ATP/BzATP. Meanwhile, rhein reduced ATP/BzATP-induced IL-1β release in lipopolysaccharide-activated macrophages. Prolonged application of ATP caused macrophage apoptosis, while the presence of rhein suppressed this cell cytotoxicity. Such ATP/BzATP-induced cellular reactions were also inhibited by a well-known rat P2X(7) receptor antagonist, brilliant blue G, in a similar way to rhein. Together, our results demonstrate that rhein inhibit ATP/BzATP-induced [Ca(2+)](c) increase, pore formation, ROS production, phagocytosis attenuation, IL-1β release and cell apoptosis by antagonizing the P2X(7) receptor in rat peritoneal macrophages. Nature Publishing Group 2015-09-10 /pmc/articles/PMC4564849/ /pubmed/26354875 http://dx.doi.org/10.1038/srep14012 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Hu, Fen Xing, Fulin Zhu, Ge Xu, Guangxue Li, Cunbo Qu, Junle Lee, Imshik Pan, Leiting Rhein antagonizes P2X(7) receptor in rat peritoneal macrophages |
title | Rhein antagonizes P2X(7) receptor in rat peritoneal macrophages |
title_full | Rhein antagonizes P2X(7) receptor in rat peritoneal macrophages |
title_fullStr | Rhein antagonizes P2X(7) receptor in rat peritoneal macrophages |
title_full_unstemmed | Rhein antagonizes P2X(7) receptor in rat peritoneal macrophages |
title_short | Rhein antagonizes P2X(7) receptor in rat peritoneal macrophages |
title_sort | rhein antagonizes p2x(7) receptor in rat peritoneal macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564849/ https://www.ncbi.nlm.nih.gov/pubmed/26354875 http://dx.doi.org/10.1038/srep14012 |
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