GABA, a natural immunomodulator of T lymphocytes

被引：150

作者：

Bjurstrom, Helen ^{[1
]}

Wang, JunYang ^{[2
,3
]}

Ericsson, Ida ^{[2
]}

Bengtsson, Martin ^{[1
]}

Liu, Yawei ^{[2
,3
]}

Kurnar-Mendu, Suresh ^{[1
]}

Issazadeh-Navikas, Shohreh ^{[2
,3
]}

Birnir, Bryndis ^{[1
]}

机构：

[1] Lund Univ, CRC, Ctr Diabet, Dept Clin Sci, Malmo 20502, Sweden

[2] BMC, Neuroinflammat Unit, Lund, Sweden

[3] Univ Copenhagen, Biotech Res & Innovat Ctr, Neuroinflammat Unit, Copenhagen, Denmark

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2008年 / 205卷 / 1-2期

基金：

瑞典研究理事会;

关键词：

GABAA; Tonic current; Inhibition; T cell;

D O I：

10.1016/j.jneuroim.2008.08.017

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could be activated by the low (nM-1 mu M), physiological concentrations of GABA present around neurons in the brain. The cells expressed the alpha 1, alpha 4, beta 2, beta 3, gamma 1 and delta GABAA channel subunits and formed functional, extrasynaptic-like GABA channels that were activated by 1 mu M GABA. 100 nM and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory. (C) 2008 Elsevier B.V. All rights reserved

引用

页码：44 / 50

页数：7

共 33 条

[1] Human peripheral blood mononuclear cells express GABAA receptor subunits [J].

Alam, S ;

Laughton, DL ;

Walding, A ;

Wolstenholme, AJ .

MOLECULAR IMMUNOLOGY, 2006, 43 (09) :1432-1442

[2] Potassium channels, memory T cells, and multiple sclerosis [J].

Beeton, C ;

Chandy, KG .

NEUROSCIENTIST, 2005, 11 (06) :550-562

[3] GABA modulates cytotoxicity of immunocompetent cells expressing GABAA receptor subunits [J].

Bergeret, M ;

Khrestchatisky, M ;

Tremblay, E ;

Bernard, A ;

Gregoire, A ;

Chany, C .

BIOMEDICINE & PHARMACOTHERAPY, 1998, 52 (05) :214-219

[4] The impact of sub-cellular location and intracellular neuronal proteins on properties of GABAA receptors [J].

Birnir, Bryndis ;

Korpi, Esa R. .

CURRENT PHARMACEUTICAL DESIGN, 2007, 13 (31) :3169-3177

[5] Plasma GABA levels correlate with aggressiveness in relatives of patients with unipolar depressive disorder [J].

Bjork, JM ;

Moeller, FG ;

Kramer, GL ;

Kram, M ;

Suris, A ;

Rush, AJ ;

Petty, F .

PSYCHIATRY RESEARCH, 2001, 101 (02) :131-136

[6] K+ channels as targets for specific immunomodulation [J].

Chandy, KG ;

Wulff, H ;

Beeton, C ;

Pennington, M ;

Gutman, GA ;

Cahalan, MD .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2004, 25 (05) :280-289

[7] GABAA receptor associated proteins:: a key factor regulating GABAA receptor function [J].

Chen, Zi-Wei ;

Olsen, Richard W. .

JOURNAL OF NEUROCHEMISTRY, 2007, 100 (02) :279-294

[8] Exposure to novelty and forced swimming evoke stressor-dependent changes in extracellular GABA in the rat hippocampus [J].

de Groote, L. ;

Linthorst, A. C. E. .

NEUROSCIENCE, 2007, 148 (03) :794-805

[9] Conductance of recombinant GABAA channels is increased in cells co-expressing GABAA receptor-associated protein [J].

Everitt, AB ;

Luu, T ;

Cromer, B ;

Tierney, ML ;

Birnir, B ;

Olsen, RW ;

Gage, PW .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (21) :21701-21706

[10] GODZ-mediated palmitoylation of GABAA receptors is required for normal assembly and function of GABAergic inhibitory synapses [J].

Fang, Cheng ;

Deng, Lunbin ;

Keller, Cheryl A. ;

Fukata, Masaki ;

Fukata, Yuko ;

Chen, Gong ;

Luscher, Bernhard .

JOURNAL OF NEUROSCIENCE, 2006, 26 (49) :12758-12768

← 1 2 3 4 →