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Lovastatin blocks Kv1.3 channel in human T cells: a new mechanism to explain its immunomodulatory properties.

Lovastatin is a member of Statins, which are beneficial in a lot of immunologic cardiovascular diseases and T cell-mediated autoimmune diseases. Kv1.3 channel plays important roles in the activation and proliferation of T cells, and have become attractive target for immune-related disorders. The pre... Full description

Journal Title: Scientific reports November 30, 2015, Vol.5, p.17381
Main Author: Zhao, Ning
Other Authors: Dong, Qian , Qian, Cheng , Li, Sen , Wu, Qiong-Feng , Ding, Dan , Li, Jing , Wang, Bin-Bin , Guo, Ke-Fang , Xie, Jiang-Jiao , Cheng, Xiang , Liao, Yu-Hua , Du, Yi-Mei
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 2045-2322 ; DOI: 10.1038/srep17381
Link: http://search.proquest.com/docview/1738482352/?pq-origsite=primo
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title: Lovastatin blocks Kv1.3 channel in human T cells: a new mechanism to explain its immunomodulatory properties.
format: Article
creator:
  • Zhao, Ning
  • Dong, Qian
  • Qian, Cheng
  • Li, Sen
  • Wu, Qiong-Feng
  • Ding, Dan
  • Li, Jing
  • Wang, Bin-Bin
  • Guo, Ke-Fang
  • Xie, Jiang-Jiao
  • Cheng, Xiang
  • Liao, Yu-Hua
  • Du, Yi-Mei
subjects:
  • Calcium–Metabolism
  • Cell Proliferation–Drug Effects
  • Gene Expression Regulation–Drug Effects
  • Humans–Drug Effects
  • Immunomodulation–Metabolism
  • Interleukin-2–Antagonists & Inhibitors
  • Jurkat Cells–Genetics
  • Kv1.3 Potassium Channel–Metabolism
  • Large-Conductance Calcium-Activated Potassium Channels–Metabolism
  • Lovastatin–Pharmacology
  • Membrane Potentials–Drug Effects
  • Mutation–Metabolism
  • Nf-Kappa B–Metabolism
  • Nfatc Transcription Factors–Pharmacology
  • Potassium Channel Blockers–Drug Effects
  • T-Lymphocytes–Immunology
  • T-Lymphocytes–Metabolism
  • Interleukin-2
  • Kv1.3 Potassium Channel
  • Large-Conductance Calcium-Activated Potassium Channels
  • Nf-Kappa B
  • Nfatc Transcription Factors
  • Potassium Channel Blockers
  • Lovastatin
  • Calcium
ispartof: Scientific reports, November 30, 2015, Vol.5, p.17381
description: Lovastatin is a member of Statins, which are beneficial in a lot of immunologic cardiovascular diseases and T cell-mediated autoimmune diseases. Kv1.3 channel plays important roles in the activation and proliferation of T cells, and have become attractive target for immune-related disorders. The present study was designed to examine the block effect of Lovastatin on Kv1.3 channel in human T cells, and to clarify its new immunomodulatory mechanism. We found that Lovastatin inhibited Kv1.3 currents in a concentration- and voltage-dependent manner, and the IC50 for peak, end of the pulse was 39.81 ± 5.11, 6.92 ± 0.95 μM, respectively. Lovastatin also accelerated the decay rate of current inactivation and negatively shifted the steady-state inactivation curves concentration-dependently, without affecting the activation curve. However, 30 μM Lovastatin had no apparent effect on KCa current in human T cells. Furthermore, Lovastatin inhibited Ca(2+) influx, T cell proliferation as well as IL-2 production. The activities of NFAT1 and NF-κB p65/50 were down-regulated by Lovastatin, too. At last, Mevalonate application only partially reversed the inhibition of Lovastatin on IL-2 secretion, and the siRNA against Kv1.3 also partially reduced this inhibitory effect of Lovastatin. In conclusion, Lovastatin can exert immunodulatory properties through the new mechanism of blocking Kv1.3 channel.
language: eng
source:
identifier: E-ISSN: 2045-2322 ; DOI: 10.1038/srep17381
fulltext: fulltext
issn:
  • 20452322
  • 2045-2322
url: Link


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titleLovastatin blocks Kv1.3 channel in human T cells: a new mechanism to explain its immunomodulatory properties.
creatorZhao, Ning ; Dong, Qian ; Qian, Cheng ; Li, Sen ; Wu, Qiong-Feng ; Ding, Dan ; Li, Jing ; Wang, Bin-Bin ; Guo, Ke-Fang ; Xie, Jiang-Jiao ; Cheng, Xiang ; Liao, Yu-Hua ; Du, Yi-Mei
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ispartofScientific reports, November 30, 2015, Vol.5, p.17381
identifierE-ISSN: 2045-2322 ; DOI: 10.1038/srep17381
subjectCalcium–Metabolism ; Cell Proliferation–Drug Effects ; Gene Expression Regulation–Drug Effects ; Humans–Drug Effects ; Immunomodulation–Metabolism ; Interleukin-2–Antagonists & Inhibitors ; Jurkat Cells–Genetics ; Kv1.3 Potassium Channel–Metabolism ; Large-Conductance Calcium-Activated Potassium Channels–Metabolism ; Lovastatin–Pharmacology ; Membrane Potentials–Drug Effects ; Mutation–Metabolism ; Nf-Kappa B–Metabolism ; Nfatc Transcription Factors–Pharmacology ; Potassium Channel Blockers–Drug Effects ; T-Lymphocytes–Immunology ; T-Lymphocytes–Metabolism ; Interleukin-2 ; Kv1.3 Potassium Channel ; Large-Conductance Calcium-Activated Potassium Channels ; Nf-Kappa B ; Nfatc Transcription Factors ; Potassium Channel Blockers ; Lovastatin ; Calcium
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descriptionLovastatin is a member of Statins, which are beneficial in a lot of immunologic cardiovascular diseases and T cell-mediated autoimmune diseases. Kv1.3 channel plays important roles in the activation and proliferation of T cells, and have become attractive target for immune-related disorders. The present study was designed to examine the block effect of Lovastatin on Kv1.3 channel in human T cells, and to clarify its new immunomodulatory mechanism. We found that Lovastatin inhibited Kv1.3 currents in a concentration- and voltage-dependent manner, and the IC50 for peak, end of the pulse was 39.81 ± 5.11, 6.92 ± 0.95 μM, respectively. Lovastatin also accelerated the decay rate of current inactivation and negatively shifted the steady-state inactivation curves concentration-dependently, without affecting the activation curve. However, 30 μM Lovastatin had no apparent effect on KCa current in human T cells. Furthermore, Lovastatin inhibited Ca(2+) influx, T cell proliferation as well as IL-2 production. The activities of NFAT1 and NF-κB p65/50 were down-regulated by Lovastatin, too. At last, Mevalonate application only partially reversed the inhibition of Lovastatin on IL-2 secretion, and the siRNA against Kv1.3 also partially reduced this inhibitory effect of Lovastatin. In conclusion, Lovastatin can exert immunodulatory properties through the new mechanism of blocking Kv1.3 channel.
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titleLovastatin blocks Kv1.3 channel in human T cells: a new mechanism to explain its immunomodulatory properties.
authorZhao, Ning ; Dong, Qian ; Qian, Cheng ; Li, Sen ; Wu, Qiong-Feng ; Ding, Dan ; Li, Jing ; Wang, Bin-Bin ; Guo, Ke-Fang ; Xie, Jiang-Jiao ; Cheng, Xiang ; Liao, Yu-Hua ; Du, Yi-Mei
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6Jurkat Cells–Genetics
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10Membrane Potentials–Drug Effects
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20Nf-Kappa B
21Nfatc Transcription Factors
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