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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 |
2010-2-10
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pubmed:abstractText |
Recent advances in the knowledge of the EGFR pathway have revealed its contribution to distinct immune/inflammatory functions of the epidermis. The purpose of our study was to evaluate the role of EGFR in the regulation of keratinocyte GM-CSF expression. In cultured human keratinocytes, proinflammatory cytokines synergized with TGF-alpha to induce GM-CSF expression. Accordingly, high epidermal levels of EGFR activation are associated with enhanced expression of GM-CSF in lesional skin of patients with psoriasis or allergic contact dermatitis. In cultured keratinocytes, pharmacological inhibition of EGFR activity reduced GM-CSF promoter transactivation, whereas genetic inhibition of AP-1 reduced expression of GM-CSF. Furthermore, EGFR activation enhanced TNF-alpha-induced c-Jun phosphorylation and DNA binding, whereas c-Jun silencing reduced GM-CSF expression. Using two different mouse models, we showed that the lack of a functional EGFR pathway was associated with reduced cytokine-induced phosphorylation of ERK1/2, JNK1/2, c-Jun and reduced keratinocyte-derived GM-CSF expression both in vitro and in vivo. Finally, the analysis of GM-CSF expression in the skin of cancer patients treated with anti EGFR drugs showed an association between ERK activity, c-Jun phosphorylation, and epidermal GM-CSF expression. These data demonstrate that the EGFR pathway is critical for the upregulation of keratinocyte GM-CSF expression under conditions of cytokine stimulation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/cetuximab
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1523-1747
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pubmed:author |
pubmed-author:AmerioPaoloP,
pubmed-author:CataissonChristopheC,
pubmed-author:ChandrasekharaChinmayiC,
pubmed-author:GirolomoniGiampieroG,
pubmed-author:LeeTang-ChengTC,
pubmed-author:MarianiValentinaV,
pubmed-author:MasciaFrancescaF,
pubmed-author:PastoreSaveriaS,
pubmed-author:Souto AdevaGemaG,
pubmed-author:ThreadgillDavidD,
pubmed-author:YuspaStuart HSH
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pubmed:issnType |
Electronic
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pubmed:volume |
130
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
682-93
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pubmed:meshHeading |
pubmed-meshheading:19890352-Adult,
pubmed-meshheading:19890352-Aged,
pubmed-meshheading:19890352-Animals,
pubmed-meshheading:19890352-Antibodies, Monoclonal,
pubmed-meshheading:19890352-Antineoplastic Agents,
pubmed-meshheading:19890352-Cells, Cultured,
pubmed-meshheading:19890352-Dermatitis, Atopic,
pubmed-meshheading:19890352-Drug Eruptions,
pubmed-meshheading:19890352-Female,
pubmed-meshheading:19890352-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:19890352-Humans,
pubmed-meshheading:19890352-Interferon-gamma,
pubmed-meshheading:19890352-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:19890352-Keratinocytes,
pubmed-meshheading:19890352-MAP Kinase Signaling System,
pubmed-meshheading:19890352-Male,
pubmed-meshheading:19890352-Mice,
pubmed-meshheading:19890352-Mice, Inbred Strains,
pubmed-meshheading:19890352-Mice, Mutant Strains,
pubmed-meshheading:19890352-Middle Aged,
pubmed-meshheading:19890352-Phosphorylation,
pubmed-meshheading:19890352-Psoriasis,
pubmed-meshheading:19890352-Receptor, Epidermal Growth Factor,
pubmed-meshheading:19890352-Transcription, Genetic,
pubmed-meshheading:19890352-Transforming Growth Factor alpha
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pubmed:year |
2010
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pubmed:articleTitle |
EGFR regulates the expression of keratinocyte-derived granulocyte/macrophage colony-stimulating factor in vitro and in vivo.
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pubmed:affiliation |
Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. masciaf@mail.nih.gov
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Intramural
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