Upregulation of KCa3.1 K+ channel in mesenteric lymph node CD4+ T lymphocytes from a mouse model of dextran sodium sulfate-induced inflammatory bowel disease

Susumu Ohya, Yuka Fukuyo, Hiroaki Kito, Rina Shibaoka, Miki Matsui, Hiroki Niguma, Yasuhiro Maeda, Hisao Yamamura, Masanori Fujii, Kazunori Kimura, Yuji Imaizumi

研究成果: Article査読

26 被引用数 (Scopus)

抄録

The intermediate-conductance Ca2+-activated K+ channel KCa3.1/KCNN4 plays an important role in the modulation of Ca2+ signaling through the control of the membrane potential in T lymphocytes. Here, we study the involvement of KCa3.1 in the enlargement of the mesenteric lymph nodes (MLNs in a mouse model of inflammatory bowel disease (IBD. The mouse model of IBD was prepared by exposing male C57BL/6J mice to 5% dextran sulfate sodium for 7 days. Inflammation-induced changes in KCa3.1 activity and the expressions of KCa3.1 and its regulators in MLN CD4+ T lymphocytes were monitored by real-time PCR, Western blot, voltage-sensitive dye imaging, patch-clamp, and flow cytometric analyses. Concomitant with an upregulation of KCa3.1a and nucleoside diphosphate kinase B (NDPK-B, a positive KCa3.1 regulator, an increase in KCa3.1 activity was observed in MLN CD4+ T lymphocytes in the IBD model. Pharmacological blockade of KCa3.1 elicited the following results: 1 a significant decrease in IBD disease severity, as assessed by diarrhea, visible fecal blood, inflammation, and crypt damage of the colon and MLN enlargement compared with control mice, and 2 the restoration of the expression levels of KCa3.1a, NDPK-B, and Th1 cytokines in IBD model MLN CD4+ T lymphocytes. These findings suggest that the increase in KCa3.1 activity induced by the upregulation of KCa3.1a and NDPK-B may be involved in the pathogenesis of IBD by mediating the enhancement of the proliferative response in MLN CD4+ T lymphocyte and, therefore, that the pharmacological blockade of KCa3.1 may decrease the risk of IBD.

本文言語English
ページ(範囲)G873-G885
ジャーナルAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
306
10
DOI
出版ステータスPublished - 15-05-2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生理学
  • 肝臓学
  • 消化器病学
  • 生理学(医学)

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「Upregulation of K<sub>Ca</sub>3.1 K<sup>+</sup> channel in mesenteric lymph node CD4<sup>+</sup> T lymphocytes from a mouse model of dextran sodium sulfate-induced inflammatory bowel disease」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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