| pubmed-article:14688310 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:14688310 | lifeskim:mentions | umls-concept:C0123759 | lld:lifeskim |
| pubmed-article:14688310 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
| pubmed-article:14688310 | lifeskim:mentions | umls-concept:C1423842 | lld:lifeskim |
| pubmed-article:14688310 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:14688310 | lifeskim:mentions | umls-concept:C1527148 | lld:lifeskim |
| pubmed-article:14688310 | lifeskim:mentions | umls-concept:C1546857 | lld:lifeskim |
| pubmed-article:14688310 | lifeskim:mentions | umls-concept:C1556066 | lld:lifeskim |
| pubmed-article:14688310 | lifeskim:mentions | umls-concept:C1619636 | lld:lifeskim |
| pubmed-article:14688310 | lifeskim:mentions | umls-concept:C1514873 | lld:lifeskim |
| pubmed-article:14688310 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:14688310 | pubmed:dateCreated | 2003-12-22 | lld:pubmed |
| pubmed-article:14688310 | pubmed:abstractText | STAT4 is an essential transcription factor for Th1 cell development. IL-12 and IFN-alpha both activate STAT4, but with different kinetics. In this study we compared their capacities to drive differentiation of human naive Th cells toward the Th1 phenotype. The Th1-polarizing activity of IFN-alpha was much weaker than that of IL-12, correlating with a marked difference in the kinetics of STAT4 activation; the response to IL-12 was sustained (>48 h), whereas the response to IFN-alpha was transient (4 h). The continuous presence of IL-12 was required for sustained STAT4 activation. Similarly, optimal Th1 polarization was only achieved upon prolonged exposure to IL-12 and could not be induced by a transient IL-12 pulse. Furthermore, the cytokine IL-2 potentiated sustained IL-12/STAT4 responses through up-regulation of IL-12R expression and synergized with IL-12 in driving Th1 cell development. Transient IFN-alpha responses, on the other hand, were not prolonged by IL-2. IFN-alpha treatment induced down-regulation of IFN-alphabeta receptor subunit 1, rendering cells refractory to IFN-alpha, but did not trans-inhibit the IL-12/STAT4 response. These data indicate that sustained IL-12 signaling is essential for optimal Th1 cell development and that transient activation of STAT4 in response to IFN-alpha may explain the poor Th1-polarizing capacity of this cytokine. Collectively these data show that the duration of cytokine signaling is important for determining the biological response. | lld:pubmed |
| pubmed-article:14688310 | pubmed:language | eng | lld:pubmed |
| pubmed-article:14688310 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14688310 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:14688310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14688310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14688310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14688310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14688310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14688310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14688310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14688310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14688310 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14688310 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:14688310 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:14688310 | pubmed:issn | 0022-1767 | lld:pubmed |
| pubmed-article:14688310 | pubmed:author | pubmed-author:CantrellDoree... | lld:pubmed |
| pubmed-article:14688310 | pubmed:author | pubmed-author:SmitsHermelij... | lld:pubmed |
| pubmed-article:14688310 | pubmed:author | pubmed-author:HilkensCathar... | lld:pubmed |
| pubmed-article:14688310 | pubmed:author | pubmed-author:Athie-Morales... | lld:pubmed |
| pubmed-article:14688310 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:14688310 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:14688310 | pubmed:volume | 172 | lld:pubmed |
| pubmed-article:14688310 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:14688310 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:14688310 | pubmed:pagination | 61-9 | lld:pubmed |
| pubmed-article:14688310 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
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| pubmed-article:14688310 | pubmed:meshHeading | pubmed-meshheading:14688310... | lld:pubmed |
| pubmed-article:14688310 | pubmed:meshHeading | pubmed-meshheading:14688310... | lld:pubmed |
| pubmed-article:14688310 | pubmed:meshHeading | pubmed-meshheading:14688310... | lld:pubmed |
| pubmed-article:14688310 | pubmed:meshHeading | pubmed-meshheading:14688310... | lld:pubmed |
| pubmed-article:14688310 | pubmed:meshHeading | pubmed-meshheading:14688310... | lld:pubmed |
| pubmed-article:14688310 | pubmed:meshHeading | pubmed-meshheading:14688310... | lld:pubmed |
| pubmed-article:14688310 | pubmed:meshHeading | pubmed-meshheading:14688310... | lld:pubmed |
| pubmed-article:14688310 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:14688310 | pubmed:articleTitle | Sustained IL-12 signaling is required for Th1 development. | lld:pubmed |
| pubmed-article:14688310 | pubmed:affiliation | Lymphocyte Activation Laboratory and Biochemical Regulatory Mechanisms Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London, United Kingdom. | lld:pubmed |
| pubmed-article:14688310 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:14688310 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:14688310 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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