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TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection
Calcium signaling in phagocytes is essential for cellular activation, migration and the potential resolution of infection or inflammation. The generation of reactive oxygen species (ROS) via activation of NADPH (nicotinamide adenine dinucleotide phosphate-) oxidase activity in macrophages has been l...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5250617/ https://www.ncbi.nlm.nih.gov/pubmed/27435104 http://dx.doi.org/10.1038/mi.2016.60 |
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author | Beceiro, Susana Radin, Jana N. Chatuvedi, Rupesh Piazuelo, M. Blanca Horvarth, Dennis J. Cortado, Hanna Gu, Yuanzheng Dixon, Beverly Gu, Chen Lange, Ingo Koomoa, Dana-Lynn T. Wilson, Keith T. Scott Algood, Holly M. Partida-Sánchez, Santiago |
author_facet | Beceiro, Susana Radin, Jana N. Chatuvedi, Rupesh Piazuelo, M. Blanca Horvarth, Dennis J. Cortado, Hanna Gu, Yuanzheng Dixon, Beverly Gu, Chen Lange, Ingo Koomoa, Dana-Lynn T. Wilson, Keith T. Scott Algood, Holly M. Partida-Sánchez, Santiago |
author_sort | Beceiro, Susana |
collection | PubMed |
description | Calcium signaling in phagocytes is essential for cellular activation, migration and the potential resolution of infection or inflammation. The generation of reactive oxygen species (ROS) via activation of NADPH (nicotinamide adenine dinucleotide phosphate-) oxidase activity in macrophages has been linked to altered intracellular calcium concentrations. Because of its role as an oxidative stress sensor in phagocytes, we investigated the function of the cation channel transient receptor potential melastatin 2 (TRPM2) in macrophages during oxidative stress responses induced by Helicobacter pylori infection. We show that Trpm2(−/−) mice, when chronically infected with H. pylori, exhibit increased gastric inflammation and decreased bacterial colonization compared with WT mice. The absence of TRPM2 triggers greater macrophage production of inflammatory mediators and promotes classically activated macrophage M1 polarization in response to H. pylori. TRPM2-deficient macrophages upon H. pylori stimulation are unable to control intracellular calcium levels, which results in calcium overloading. Furthermore, increased intracellular calcium in TRPM2(−/−) macrophages enhanced MAPK and NADPH oxidase activities, compared to WT macrophages. Our data suggest that augmented production of ROS and inflammatory cytokines with TRPM2 deletion regulates oxidative stress in macrophages, and consequently, decreases H. pylori gastric colonization while increasing inflammation in the gastric mucosa. |
format | Online Article Text |
id | pubmed-5250617 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-52506172017-03-06 TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection Beceiro, Susana Radin, Jana N. Chatuvedi, Rupesh Piazuelo, M. Blanca Horvarth, Dennis J. Cortado, Hanna Gu, Yuanzheng Dixon, Beverly Gu, Chen Lange, Ingo Koomoa, Dana-Lynn T. Wilson, Keith T. Scott Algood, Holly M. Partida-Sánchez, Santiago Mucosal Immunol Article Calcium signaling in phagocytes is essential for cellular activation, migration and the potential resolution of infection or inflammation. The generation of reactive oxygen species (ROS) via activation of NADPH (nicotinamide adenine dinucleotide phosphate-) oxidase activity in macrophages has been linked to altered intracellular calcium concentrations. Because of its role as an oxidative stress sensor in phagocytes, we investigated the function of the cation channel transient receptor potential melastatin 2 (TRPM2) in macrophages during oxidative stress responses induced by Helicobacter pylori infection. We show that Trpm2(−/−) mice, when chronically infected with H. pylori, exhibit increased gastric inflammation and decreased bacterial colonization compared with WT mice. The absence of TRPM2 triggers greater macrophage production of inflammatory mediators and promotes classically activated macrophage M1 polarization in response to H. pylori. TRPM2-deficient macrophages upon H. pylori stimulation are unable to control intracellular calcium levels, which results in calcium overloading. Furthermore, increased intracellular calcium in TRPM2(−/−) macrophages enhanced MAPK and NADPH oxidase activities, compared to WT macrophages. Our data suggest that augmented production of ROS and inflammatory cytokines with TRPM2 deletion regulates oxidative stress in macrophages, and consequently, decreases H. pylori gastric colonization while increasing inflammation in the gastric mucosa. 2016-07-20 2017-03 /pmc/articles/PMC5250617/ /pubmed/27435104 http://dx.doi.org/10.1038/mi.2016.60 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Beceiro, Susana Radin, Jana N. Chatuvedi, Rupesh Piazuelo, M. Blanca Horvarth, Dennis J. Cortado, Hanna Gu, Yuanzheng Dixon, Beverly Gu, Chen Lange, Ingo Koomoa, Dana-Lynn T. Wilson, Keith T. Scott Algood, Holly M. Partida-Sánchez, Santiago TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection |
title | TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection |
title_full | TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection |
title_fullStr | TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection |
title_full_unstemmed | TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection |
title_short | TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection |
title_sort | trpm2 ion channels regulate macrophage polarization and gastric inflammation during helicobacter pylori infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5250617/ https://www.ncbi.nlm.nih.gov/pubmed/27435104 http://dx.doi.org/10.1038/mi.2016.60 |
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