Linked Life Data

19050239

Source:http://linkedlifedata.com/resource/pubmed/id/19050239

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-12-3
pubmed:abstractText
gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the CNS, and GABA transporter 1 (GAT-1) is critical in maintaining a GABA reservoir and associated functions. The wide expression of GAT-1 in the CNS prompted us to explore its role in neuroimmunological disorders. In mice induced with experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, we found that the expression levels of GAT-1 mRNA and protein in spinal cord were greatly suppressed as compared with those in naive mice and irrelevant Ag-immunized mice. Therefore, we induced EAE in GAT-1(-/-) mice and found that the disease was significantly aggravated and was accompanied by some nonclassic EAE signs. Mononuclear cells from GAT-1(-/-) mice with EAE showed much higher Ag-specific proliferative responses. Proinflammatory cytokine production in these mice was also greatly up-regulated. Further studies revealed that GAT-1 deficiency induced vigorous immune responses by enhancing IkappaB kinase phosphorylation and NF-kappaB-DNA binding activity, as well as strengthening the T-bet-STAT1 circuit signaling pathway. Finally, we found that GAT-1 was expressed only on activated T cells primed with Ags, but not on B cells or macrophages. These findings indicate that GAT-1 is a critical modulator in T cell-mediated immune responses and in EAE pathogenesis.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
181
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8226-36
pubmed:dateRevised
2009-3-30
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Gamma-aminobutyric acid transporter 1 negatively regulates T cell-mediated immune responses and ameliorates autoimmune inflammation in the CNS.
pubmed:affiliation
Institute of Health Sciences, Shanghai Jiaotong University School of Medicine, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't