Source:http://linkedlifedata.com/resource/pubmed/id/21106245
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2011-1-3
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pubmed:abstractText |
Challenge of human mast cells with both stem cell factor (SCF) and IL-4 enhances antigen-dependent mediator release raising the assumption of intracellular crosstalk between the IL-4, SCF, and Fc?RI signaling pathways. Here, we analyzed the intracellular crosstalk of IL-4-, SCF-, and IgE-dependent activation pathways in mucosal mast cells isolated from human intestine. The release of ?-hexosaminidase, leukotriene C(4), and IL-8, but not IL-6, was strongly enhanced in response to sequential challenge of mast cells with IL-4, SCF and Fc?RI cross-linking compared to stimulation by Fc?RI cross-linking alone. Previous studies revealed that MAPK and other serine/threonine kinases are involved in mast cell activation processes. Here we found that activation of mast cells by Fc?RI cross-linking alone results in phosphorylation of ERK and p38, but not of Akt. Stimulation with SCF alone also induced phosphorylation of ERK and p38, and additionally of Akt. IL-4 priming enhanced activation of ERK, but blocked activation of p38. Activation of p38 was required for IL-6 production explaining the inhibitory effect of IL-4 on IL-6 expression in human mast cells. Moreover, IL-4 priming that anteceded Fc?RI cross-linking induced activation of Akt. The combined challenge of mast cells with IL-4, SCF and Fc?RI cross-linking substantially up-regulated activation of Akt, whereas blocking of Akt inhibited the pronounced production and release of IL-8 in response to the three mast cell agonists. In summary, our data demonstrate that ERK, p38, and especially Akt play an important role in cross-linking IL-4 priming, SCF signaling, and IgE-dependent activation of mature human mast cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin E,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, IgE,
http://linkedlifedata.com/resource/pubmed/chemical/Stem Cell Factor,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1872-9142
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pubmed:author | |
pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
546-52
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pubmed:meshHeading |
pubmed-meshheading:21106245-Cell Differentiation,
pubmed-meshheading:21106245-Cross-Linking Reagents,
pubmed-meshheading:21106245-Enzyme Activation,
pubmed-meshheading:21106245-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:21106245-Humans,
pubmed-meshheading:21106245-Immunoglobulin E,
pubmed-meshheading:21106245-Inflammation Mediators,
pubmed-meshheading:21106245-Interleukin-4,
pubmed-meshheading:21106245-Interleukin-6,
pubmed-meshheading:21106245-Mast Cells,
pubmed-meshheading:21106245-Phosphorylation,
pubmed-meshheading:21106245-Protein Kinase Inhibitors,
pubmed-meshheading:21106245-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:21106245-Receptors, IgE,
pubmed-meshheading:21106245-Signal Transduction,
pubmed-meshheading:21106245-Stem Cell Factor,
pubmed-meshheading:21106245-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2011
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pubmed:articleTitle |
Akt cross-links IL-4 priming, stem cell factor signaling, and IgE-dependent activation in mature human mast cells.
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pubmed:affiliation |
Department of Nutritional Medicine, University of Hohenheim, Fruwirthstraße 12, 70593 Stuttgart, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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