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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...

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Autores principales: Hu, Fen, Xing, Fulin, Zhu, Ge, Xu, Guangxue, Li, Cunbo, Qu, Junle, Lee, Imshik, Pan, Leiting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
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.
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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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