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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-1-3
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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...
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1872-9142
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
546-52
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
pubmed:year
2011
pubmed:articleTitle
Akt cross-links IL-4 priming, stem cell factor signaling, and IgE-dependent activation in mature human mast cells.
pubmed:affiliation
Department of Nutritional Medicine, University of Hohenheim, Fruwirthstraße 12, 70593 Stuttgart, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't