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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2001-7-23
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pubmed:abstractText |
IL-12 and IL-18 are both proinflammatory cytokines that contribute to promoting Th1 development and IFN-gamma expression. However, neither IL-12R nor IL-18R is expressed as a functional complex on most resting T cells. This study investigated the molecular mechanisms underlying the induction of an IL-18R complex in T cells. Resting T cells expressed IL-18Ralpha chains but did not exhibit IL-18 binding sites as detected by incubation with rIL-18 followed by anti-IL-18 Ab, suggesting a lack of IL-18Rbeta expression in resting T cells. Although they also failed to express IL-12R, stimulation with anti-CD3 plus anti-CD28 generated IL-12R. Exposure of these cells to IL-12 led not only to up-regulation of IL-18Ralpha expression but also to induction of IL-18R binding sites on both CD4(+) and CD8(+) T cells concomitant with IL-18Rbeta mRNA expression. The IL-18 binding site represented a functional IL-18R complex capable of exhibiting IL-18 responsiveness. IL-12 induction of an IL-18R complex and IL-18Rbeta mRNA expression was not observed in STAT4-deficient (STAT4(-/-)) T cells and was substantially decreased in IFN-gamma(-/-) T cells. However, the failure of STAT4(-/-) T cells to induce an IL-18R complex was not corrected by IFN-gamma. These results indicate that STAT4 and IFN-gamma play an indispensable role and a role as an amplifying factor, respectively, in IL-12 induction of the functional IL-18R complex.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Il18r1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18 Receptor alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/STAT4 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
167
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1306-12
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11466347-Adjuvants, Immunologic,
pubmed-meshheading:11466347-Animals,
pubmed-meshheading:11466347-Binding Sites,
pubmed-meshheading:11466347-Cells, Cultured,
pubmed-meshheading:11466347-DNA-Binding Proteins,
pubmed-meshheading:11466347-Interferon-gamma,
pubmed-meshheading:11466347-Interleukin-12,
pubmed-meshheading:11466347-Interleukin-18 Receptor alpha Subunit,
pubmed-meshheading:11466347-Interphase,
pubmed-meshheading:11466347-Mice,
pubmed-meshheading:11466347-Mice, Inbred BALB C,
pubmed-meshheading:11466347-Mice, Knockout,
pubmed-meshheading:11466347-NF-kappa B,
pubmed-meshheading:11466347-RNA, Messenger,
pubmed-meshheading:11466347-Receptors, Antigen, T-Cell,
pubmed-meshheading:11466347-Receptors, Interleukin,
pubmed-meshheading:11466347-Receptors, Interleukin-18,
pubmed-meshheading:11466347-STAT4 Transcription Factor,
pubmed-meshheading:11466347-Signal Transduction,
pubmed-meshheading:11466347-T-Lymphocytes,
pubmed-meshheading:11466347-Trans-Activators,
pubmed-meshheading:11466347-Up-Regulation
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pubmed:year |
2001
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pubmed:articleTitle |
An absolute requirement for STAT4 and a role for IFN-gamma as an amplifying factor in IL-12 induction of the functional IL-18 receptor complex.
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pubmed:affiliation |
Department of Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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