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Pathophysiological significance of the two-pore domain K(+) channel K(2P)5.1 in splenic CD4(+)CD25(−) T cell subset from a chemically-induced murine inflammatory bowel disease model

The alkaline pH-activated, two-pore domain K(+) channel K(2P)5.1 (also known as TASK2/KCNK5) plays an important role in maintaining the resting membrane potential, and contributes to the control of Ca(2+) signaling in several types of cells. Recent studies highlighted the potential role of the K(2P)...

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Autores principales: Nakakura, Sawa, Matsui, Miki, Sato, Aya, Ishii, Mizuki, Endo, Kyoko, Muragishi, Sayaka, Murase, Miki, Kito, Hiroaki, Niguma, Hiroki, Kurokawa, Natsumi, Fujii, Masanori, Araki, Masatake, Araki, Kimi, Ohya, Susumu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621418/
https://www.ncbi.nlm.nih.gov/pubmed/26578971
http://dx.doi.org/10.3389/fphys.2015.00299
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author Nakakura, Sawa
Matsui, Miki
Sato, Aya
Ishii, Mizuki
Endo, Kyoko
Muragishi, Sayaka
Murase, Miki
Kito, Hiroaki
Niguma, Hiroki
Kurokawa, Natsumi
Fujii, Masanori
Araki, Masatake
Araki, Kimi
Ohya, Susumu
author_facet Nakakura, Sawa
Matsui, Miki
Sato, Aya
Ishii, Mizuki
Endo, Kyoko
Muragishi, Sayaka
Murase, Miki
Kito, Hiroaki
Niguma, Hiroki
Kurokawa, Natsumi
Fujii, Masanori
Araki, Masatake
Araki, Kimi
Ohya, Susumu
author_sort Nakakura, Sawa
collection PubMed
description The alkaline pH-activated, two-pore domain K(+) channel K(2P)5.1 (also known as TASK2/KCNK5) plays an important role in maintaining the resting membrane potential, and contributes to the control of Ca(2+) signaling in several types of cells. Recent studies highlighted the potential role of the K(2P)5.1 K(+) channel in the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The aim of the present study was to elucidate the pathological significance of the K(2P)5.1 K(+) channel in inflammatory bowel disease (IBD). The degrees of colitis, colonic epithelial damage, and colonic inflammation were quantified in the dextran sulfate sodium-induced mouse IBD model by macroscopic and histological scoring systems. The expression and functional activity of K(2P)5.1 in splenic CD4(+) T cells were measured using real-time PCR, Western blot, and fluorescence imaging assays. A significant increase was observed in the expression of K(2P)5.1 in the splenic CD4(+) T cells of the IBD model. Concomitant with this increase, the hyperpolarization response induced by extracellular alkaline pH was significantly larger in the IBD model with the corresponding intracellular Ca(2+) rises. The expression of K(2P)5.1 was higher in CD4(+)CD25(−) T cells than in CD4(+)CD25(+) regulatory T cells. The knockout of K(2P)5.1 in mice significantly suppressed the disease responses implicated in the IBD model. Alternations in intracellular Ca(2+) signaling following the dysregulated expression of K(2P)5.1 were associated with the disease pathogenesis of IBD. The results of the present study suggest that the K(2P)5.1 K(+) channel in CD4(+)CD25(−) T cell subset is a potential therapeutic target and biomarker for IBD.
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spelling pubmed-46214182015-11-17 Pathophysiological significance of the two-pore domain K(+) channel K(2P)5.1 in splenic CD4(+)CD25(−) T cell subset from a chemically-induced murine inflammatory bowel disease model Nakakura, Sawa Matsui, Miki Sato, Aya Ishii, Mizuki Endo, Kyoko Muragishi, Sayaka Murase, Miki Kito, Hiroaki Niguma, Hiroki Kurokawa, Natsumi Fujii, Masanori Araki, Masatake Araki, Kimi Ohya, Susumu Front Physiol Physiology The alkaline pH-activated, two-pore domain K(+) channel K(2P)5.1 (also known as TASK2/KCNK5) plays an important role in maintaining the resting membrane potential, and contributes to the control of Ca(2+) signaling in several types of cells. Recent studies highlighted the potential role of the K(2P)5.1 K(+) channel in the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The aim of the present study was to elucidate the pathological significance of the K(2P)5.1 K(+) channel in inflammatory bowel disease (IBD). The degrees of colitis, colonic epithelial damage, and colonic inflammation were quantified in the dextran sulfate sodium-induced mouse IBD model by macroscopic and histological scoring systems. The expression and functional activity of K(2P)5.1 in splenic CD4(+) T cells were measured using real-time PCR, Western blot, and fluorescence imaging assays. A significant increase was observed in the expression of K(2P)5.1 in the splenic CD4(+) T cells of the IBD model. Concomitant with this increase, the hyperpolarization response induced by extracellular alkaline pH was significantly larger in the IBD model with the corresponding intracellular Ca(2+) rises. The expression of K(2P)5.1 was higher in CD4(+)CD25(−) T cells than in CD4(+)CD25(+) regulatory T cells. The knockout of K(2P)5.1 in mice significantly suppressed the disease responses implicated in the IBD model. Alternations in intracellular Ca(2+) signaling following the dysregulated expression of K(2P)5.1 were associated with the disease pathogenesis of IBD. The results of the present study suggest that the K(2P)5.1 K(+) channel in CD4(+)CD25(−) T cell subset is a potential therapeutic target and biomarker for IBD. Frontiers Media S.A. 2015-10-27 /pmc/articles/PMC4621418/ /pubmed/26578971 http://dx.doi.org/10.3389/fphys.2015.00299 Text en Copyright © 2015 Nakakura, Matsui, Sato, Ishii, Endo, Muragishi, Murase, Kito, Niguma, Kurokawa, Fujii, Araki, Araki and Ohya. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Nakakura, Sawa
Matsui, Miki
Sato, Aya
Ishii, Mizuki
Endo, Kyoko
Muragishi, Sayaka
Murase, Miki
Kito, Hiroaki
Niguma, Hiroki
Kurokawa, Natsumi
Fujii, Masanori
Araki, Masatake
Araki, Kimi
Ohya, Susumu
Pathophysiological significance of the two-pore domain K(+) channel K(2P)5.1 in splenic CD4(+)CD25(−) T cell subset from a chemically-induced murine inflammatory bowel disease model
title Pathophysiological significance of the two-pore domain K(+) channel K(2P)5.1 in splenic CD4(+)CD25(−) T cell subset from a chemically-induced murine inflammatory bowel disease model
title_full Pathophysiological significance of the two-pore domain K(+) channel K(2P)5.1 in splenic CD4(+)CD25(−) T cell subset from a chemically-induced murine inflammatory bowel disease model
title_fullStr Pathophysiological significance of the two-pore domain K(+) channel K(2P)5.1 in splenic CD4(+)CD25(−) T cell subset from a chemically-induced murine inflammatory bowel disease model
title_full_unstemmed Pathophysiological significance of the two-pore domain K(+) channel K(2P)5.1 in splenic CD4(+)CD25(−) T cell subset from a chemically-induced murine inflammatory bowel disease model
title_short Pathophysiological significance of the two-pore domain K(+) channel K(2P)5.1 in splenic CD4(+)CD25(−) T cell subset from a chemically-induced murine inflammatory bowel disease model
title_sort pathophysiological significance of the two-pore domain k(+) channel k(2p)5.1 in splenic cd4(+)cd25(−) t cell subset from a chemically-induced murine inflammatory bowel disease model
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621418/
https://www.ncbi.nlm.nih.gov/pubmed/26578971
http://dx.doi.org/10.3389/fphys.2015.00299
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