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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0021758,
umls-concept:C0024880,
umls-concept:C0031621,
umls-concept:C0035820,
umls-concept:C0085295,
umls-concept:C0185117,
umls-concept:C0591833,
umls-concept:C1335877,
umls-concept:C1690540,
umls-concept:C2911684
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pubmed:issue |
5
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pubmed:dateCreated |
1999-9-14
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pubmed:abstractText |
The c-kit protooncogene encodes a receptor tyrosine kinase that is known to play a critical role in hemopoiesis and is essential for mast cell growth, differentiation, and cytokine production. Studies have shown that the Th2 cytokine IL-4 can down-regulate Kit expression on human and murine mast cells, but the mechanism of this down-regulation has remained unresolved. Using mouse bone marrow-derived mast cells, we demonstrate that IL-4-mediated Kit down-regulation requires STAT6 expression and phosphotidylinositide-3'-kinase activation. We also find that the Th2 cytokine IL-10 potently down-regulates Kit expression. IL-4 enhances IL-10-mediated inhibition in a manner that is STAT6 independent and phosphotidylinositide-3'-kinase dependent. Both IL-4- and IL-10-mediated Kit down-regulation were coupled with little or no change in c-kit mRNA levels, no significant change in Kit protein stability, but decreased total Kit protein expression. Inhibition of Kit expression by IL-4 and IL-10 resulted in a loss of Kit-mediated signaling, as evidenced by reduced IL-13 and TNF-alpha mRNA induction after stem cell factor stimulation. These data offer a role for STAT6 and phosphotidylinositide-3'-kinase in IL-4-mediated Kit down-regulation, coupled with the novel observation that IL-10 is a potent inhibitor of Kit expression and function. Regulating Kit expression and signaling may be essential to controlling mast cell-mediated inflammatory responses.
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pubmed:grant |
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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/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-kit,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/STAT6 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stem Cell Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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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 |
163
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2530-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10452990-Adjuvants, Immunologic,
pubmed-meshheading:10452990-Animals,
pubmed-meshheading:10452990-Bone Marrow Cells,
pubmed-meshheading:10452990-Cells, Cultured,
pubmed-meshheading:10452990-Culture Techniques,
pubmed-meshheading:10452990-Cytokines,
pubmed-meshheading:10452990-DNA-Binding Proteins,
pubmed-meshheading:10452990-Down-Regulation,
pubmed-meshheading:10452990-Interleukin-10,
pubmed-meshheading:10452990-Interleukin-4,
pubmed-meshheading:10452990-Mast Cells,
pubmed-meshheading:10452990-Mice,
pubmed-meshheading:10452990-Mice, Inbred BALB C,
pubmed-meshheading:10452990-Mice, Inbred C57BL,
pubmed-meshheading:10452990-Mice, Knockout,
pubmed-meshheading:10452990-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10452990-Proto-Oncogene Proteins c-kit,
pubmed-meshheading:10452990-RNA, Messenger,
pubmed-meshheading:10452990-STAT6 Transcription Factor,
pubmed-meshheading:10452990-Stem Cell Factor,
pubmed-meshheading:10452990-Trans-Activators
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pubmed:year |
1999
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pubmed:articleTitle |
Inhibition of Kit expression by IL-4 and IL-10 in murine mast cells: role of STAT6 and phosphatidylinositol 3'-kinase.
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pubmed:affiliation |
Department of Biology, Virginia Commonwealth University, Richmond 23284, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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