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Histone Deacetylases Enhance Ca(2+)-Activated K(+) Channel K(Ca)3.1 Expression in Murine Inflammatory CD4(+) T Cells

The up-regulated expression of the Ca(2+)-activated K(+) channel K(Ca)3.1 in inflammatory CD4(+) T cells has been implicated in the pathogenesis of inflammatory bowel disease (IBD) through the enhanced production of inflammatory cytokines, such as interferon-γ (IFN-γ). However, the underlying mechan...

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Autores principales: Matsui, Miki, Terasawa, Kyoko, Kajikuri, Junko, Kito, Hiroaki, Endo, Kyoko, Jaikhan, Pattaporn, Suzuki, Takayoshi, Ohya, Susumu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213394/
https://www.ncbi.nlm.nih.gov/pubmed/30262728
http://dx.doi.org/10.3390/ijms19102942
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author Matsui, Miki
Terasawa, Kyoko
Kajikuri, Junko
Kito, Hiroaki
Endo, Kyoko
Jaikhan, Pattaporn
Suzuki, Takayoshi
Ohya, Susumu
author_facet Matsui, Miki
Terasawa, Kyoko
Kajikuri, Junko
Kito, Hiroaki
Endo, Kyoko
Jaikhan, Pattaporn
Suzuki, Takayoshi
Ohya, Susumu
author_sort Matsui, Miki
collection PubMed
description The up-regulated expression of the Ca(2+)-activated K(+) channel K(Ca)3.1 in inflammatory CD4(+) T cells has been implicated in the pathogenesis of inflammatory bowel disease (IBD) through the enhanced production of inflammatory cytokines, such as interferon-γ (IFN-γ). However, the underlying mechanisms have not yet been elucidated. The objective of the present study is to clarify the involvement of histone deacetylases (HDACs) in the up-regulation of K(Ca)3.1 in the CD4(+) T cells of IBD model mice. The expression levels of K(Ca)3.1 and its regulators, such as function-modifying molecules and transcription factors, were quantitated using a real-time polymerase chain reaction (PCR) assay, Western blotting, and depolarization responses, which were induced by the selective K(Ca)3.1 blocker TRAM-34 (1 μM) and were measured using a voltage-sensitive fluorescent dye imaging system. The treatment with 1 μM vorinostat, a pan-HDAC inhibitor, for 24 h repressed the transcriptional expression of K(Ca)3.1 in the splenic CD4(+) T cells of IBD model mice. Accordingly, TRAM-34-induced depolarization responses were significantly reduced. HDAC2 and HDAC3 were significantly up-regulated in the CD4(+) T cells of IBD model mice. The down-regulated expression of K(Ca)3.1 was observed following treatments with the selective inhibitors of HDAC2 and HDAC3. The K(Ca)3.1 K(+) channel regulates inflammatory cytokine production in CD4(+) T cells, mediating epigenetic modifications by HDAC2 and HDAC3.
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spelling pubmed-62133942018-11-14 Histone Deacetylases Enhance Ca(2+)-Activated K(+) Channel K(Ca)3.1 Expression in Murine Inflammatory CD4(+) T Cells Matsui, Miki Terasawa, Kyoko Kajikuri, Junko Kito, Hiroaki Endo, Kyoko Jaikhan, Pattaporn Suzuki, Takayoshi Ohya, Susumu Int J Mol Sci Article The up-regulated expression of the Ca(2+)-activated K(+) channel K(Ca)3.1 in inflammatory CD4(+) T cells has been implicated in the pathogenesis of inflammatory bowel disease (IBD) through the enhanced production of inflammatory cytokines, such as interferon-γ (IFN-γ). However, the underlying mechanisms have not yet been elucidated. The objective of the present study is to clarify the involvement of histone deacetylases (HDACs) in the up-regulation of K(Ca)3.1 in the CD4(+) T cells of IBD model mice. The expression levels of K(Ca)3.1 and its regulators, such as function-modifying molecules and transcription factors, were quantitated using a real-time polymerase chain reaction (PCR) assay, Western blotting, and depolarization responses, which were induced by the selective K(Ca)3.1 blocker TRAM-34 (1 μM) and were measured using a voltage-sensitive fluorescent dye imaging system. The treatment with 1 μM vorinostat, a pan-HDAC inhibitor, for 24 h repressed the transcriptional expression of K(Ca)3.1 in the splenic CD4(+) T cells of IBD model mice. Accordingly, TRAM-34-induced depolarization responses were significantly reduced. HDAC2 and HDAC3 were significantly up-regulated in the CD4(+) T cells of IBD model mice. The down-regulated expression of K(Ca)3.1 was observed following treatments with the selective inhibitors of HDAC2 and HDAC3. The K(Ca)3.1 K(+) channel regulates inflammatory cytokine production in CD4(+) T cells, mediating epigenetic modifications by HDAC2 and HDAC3. MDPI 2018-09-27 /pmc/articles/PMC6213394/ /pubmed/30262728 http://dx.doi.org/10.3390/ijms19102942 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Matsui, Miki
Terasawa, Kyoko
Kajikuri, Junko
Kito, Hiroaki
Endo, Kyoko
Jaikhan, Pattaporn
Suzuki, Takayoshi
Ohya, Susumu
Histone Deacetylases Enhance Ca(2+)-Activated K(+) Channel K(Ca)3.1 Expression in Murine Inflammatory CD4(+) T Cells
title Histone Deacetylases Enhance Ca(2+)-Activated K(+) Channel K(Ca)3.1 Expression in Murine Inflammatory CD4(+) T Cells
title_full Histone Deacetylases Enhance Ca(2+)-Activated K(+) Channel K(Ca)3.1 Expression in Murine Inflammatory CD4(+) T Cells
title_fullStr Histone Deacetylases Enhance Ca(2+)-Activated K(+) Channel K(Ca)3.1 Expression in Murine Inflammatory CD4(+) T Cells
title_full_unstemmed Histone Deacetylases Enhance Ca(2+)-Activated K(+) Channel K(Ca)3.1 Expression in Murine Inflammatory CD4(+) T Cells
title_short Histone Deacetylases Enhance Ca(2+)-Activated K(+) Channel K(Ca)3.1 Expression in Murine Inflammatory CD4(+) T Cells
title_sort histone deacetylases enhance ca(2+)-activated k(+) channel k(ca)3.1 expression in murine inflammatory cd4(+) t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213394/
https://www.ncbi.nlm.nih.gov/pubmed/30262728
http://dx.doi.org/10.3390/ijms19102942
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