Source:http://linkedlifedata.com/resource/pubmed/id/17404269
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
|
pubmed:dateCreated |
2007-4-3
|
pubmed:abstractText |
Sphingosine 1-phosphate (S1P) is a natural lipid mediator that regulates immune cell traffic, Ab production, and T cell cytokine generation by mechanisms that enhance Th2 activities. Responses to S1P are controlled principally by the diverse expression patterns of its receptors in different cells. In T cells, the type 1 (S1P(1)) and type 4 (S1P(4)) G protein-coupled receptors are predominant. S1P(1) mainly transduces effects on T cell migration and trafficking, whereas S1P(4) transduces immunosuppression via its effects on T cell proliferation and cytokine production. Using T cell-specific S1P(1) transgenic (TG) mice, we investigated the regulatory effects of the S1P-S1P(1) axis on T cell cytokine production. The production of IL-4, but not IL-2 or IFN-gamma, was significantly up-regulated >10-fold in activated CD4 T cells from S1P(1) TG mice compared with those from wild-type mice. Quantitative real-time PCR analysis revealed that IL-4 up-regulation was initiated at the mRNA level as early as 4 h after T cell activation. The up-regulation of IL-4 mRNA was mediated by c-Maf, Jun B, and Gata3 as demonstrated by increases in their protein expression and DNA-binding activities. In contrast, the expression and DNA-binding activities of T-bet, FosB, C-Fos, Jun D, Fra-1, Fra-2, and c-Jun all were identical in wild-type and TG CD4 T cells. Immunological assays showed that increased IL-4 levels induced greater production of IgE. Thus, the S1P-S1P(1) axis specifically up-regulates c-Maf, Jun B, and Gata3, which consequently enhance IL-4 production that may lead to a Th2 phenotype.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
AIM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
0022-1767
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
178
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
4885-90
|
pubmed:dateRevised |
2007-12-3
|
pubmed:meshHeading |
pubmed-meshheading:17404269-Animals,
pubmed-meshheading:17404269-CD4-Positive T-Lymphocytes,
pubmed-meshheading:17404269-Immunoglobulin E,
pubmed-meshheading:17404269-Interleukin-4,
pubmed-meshheading:17404269-Mice,
pubmed-meshheading:17404269-Mice, Inbred C57BL,
pubmed-meshheading:17404269-Mice, Transgenic,
pubmed-meshheading:17404269-RNA, Messenger,
pubmed-meshheading:17404269-Receptors, Lysosphingolipid
|
pubmed:year |
2007
|
pubmed:articleTitle |
Type 1 sphingosine 1-phosphate G protein-coupled receptor (S1P1) mediation of enhanced IL-4 generation by CD4 T cells from S1P1 transgenic mice.
|
pubmed:affiliation |
Department of Medicine and Department of Microbiology-Immunology, University of California, San Francisco, CA 94143.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|