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Role of the K(Ca)3.1 K+ channel in auricular lymph node CD4+ T-lymphocyte function of the delayed-type hypersensitivity model.

AbstractBACKGROUND AND PURPOSE:
The intermediate-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) modulates the Ca(2+) response through the control of the membrane potential in the immune system. We investigated the role of K(Ca)3.1 on the pathogenesis of delayed-type hypersensitivity (DTH) in auricular lymph node (ALN) CD4(+) T-lymphocytes of oxazolone (Ox)-induced DTH model mice.
EXPERIMENTAL APPROACH:
The expression patterns of K(Ca)3.1 and its possible transcriptional regulators were compared among ALN T-lymphocytes of three groups [non-sensitized (Ox-/-), Ox-sensitized, but non-challenged (Ox+/-) and Ox-sensitized and -challenged (Ox+/+)] using real-time polymerase chain reaction, Western blotting and flow cytometry. KCa 3.1 activity was measured by whole-cell patch clamp and the voltage-sensitive dye imaging. The effects of K(Ca)3.1 blockade were examined by the administration of selective K(Ca)3.1 blockers.
KEY RESULTS:
Significant up-regulation of K(Ca)3.1a was observed in CD4(+) T-lymphocytes of Ox+/- and Ox+/+, without any evident changes in the expression of the dominant-negative form, K(Ca)3.1b. Negatively correlated with this, the repressor element-1 silencing transcription factor (REST) was significantly down-regulated. Pharmacological blockade of K(Ca)3.1 resulted in an accumulation of the CD4(+) T-lymphocytes of Ox+/+ at the G0/G1 phase of the cell cycle, and also significantly recovered not only the pathogenesis of DTH, but also the changes in the K(Ca)3.1 expression and activity in the CD4(+) T-lymphocytes of Ox+/- and Ox+/+.
CONCLUSIONS AND IMPLICATIONS:
The up-regulation of K(Ca)3.1a in conjunction with the down-regulation of REST may be involved in CD4(+) T-lymphocyte proliferation in the ALNs of DTH model mice; and K(Ca)3.1 may be an important target for therapeutic intervention in allergy diseases such as DTH.
AuthorsSusumu Ohya, Erina Nakamura, Sayuri Horiba, Hiroaki Kito, Miki Matsui, Hisao Yamamura, Yuji Imaizumi
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 169 Issue 5 Pg. 1011-23 (Jul 2013) ISSN: 1476-5381 [Electronic] England
PMID23594188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 The British Pharmacological Society.
Chemical References
  • Adjuvants, Immunologic
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Kcnn4 protein, mouse
  • Potassium Channel Blockers
  • Pyrazoles
  • RE1-silencing transcription factor
  • Repressor Proteins
  • TRAM 34
  • Oxazolone
Topics
  • Adjuvants, Immunologic
  • Animals
  • CD4-Positive T-Lymphocytes (immunology, physiology)
  • Cell Cycle (drug effects)
  • Disease Models, Animal
  • Ear Auricle (immunology)
  • Hypersensitivity, Delayed (chemically induced, immunology, physiopathology)
  • Intermediate-Conductance Calcium-Activated Potassium Channels (antagonists & inhibitors, immunology, physiology)
  • Lymph Nodes (immunology)
  • Male
  • Mice, Inbred BALB C
  • Oxazolone
  • Potassium Channel Blockers (pharmacology)
  • Pyrazoles (pharmacology)
  • Repressor Proteins (immunology)

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