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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
1999-12-2
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pubmed:abstractText |
Upon stimulation, cutaneous sensory nerves release neuropeptides such as substance P (SP), which modulate responses in the skin by activating a number of target cells via neurokinin receptors. We have demonstrated that SP preferentially binds to the NK-1R on human dermal microvascular cells, resulting in increased intracellular Ca2+ and induction of ICAM-1 and VCAM-1 expression. In the current studies, we identify specific elements in the regulatory regions of ICAM-1 and VCAM-1 genes as necessary and sufficient for SP-dependent transcriptional activation. SP treatment of human dermal microvascular endothelial cells leads to coincident activation and binding of the transcription factor NF-AT to the -191/-170 region of the ICAM-1 gene (a region bound by activated p65/p65 homodimers in response to TNF-alpha), and NF-kappa B (p65/p50) to tandem NF-kappa B binding sites at -76/-52 of the VCAM-1 gene. The SP-elicited intracellular Ca2+ signal was required for activation and subsequent binding of both NF-AT and NF-kappa B. The transacting factor induction by SP was specific, since a selective NK-1R antagonist blocked SP activation and subsequent NF-AT and NF-kappa B activation and binding. These data demonstrate coincident activation of NF-AT and NF-kappa B via SP-induced intracellular Ca2+ mobilization and indicate a crucial role for neuropeptides in modulating localized cutaneous 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/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B p50 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-rel,
http://linkedlifedata.com/resource/pubmed/chemical/Substance P,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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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 |
15
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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 |
5656-65
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10553096-5' Untranslated Regions,
pubmed-meshheading:10553096-Calcium Signaling,
pubmed-meshheading:10553096-Cell Adhesion Molecules,
pubmed-meshheading:10553096-Cell Membrane,
pubmed-meshheading:10553096-Cells, Cultured,
pubmed-meshheading:10553096-Cyclosporine,
pubmed-meshheading:10553096-DNA-Binding Proteins,
pubmed-meshheading:10553096-Dimerization,
pubmed-meshheading:10553096-Endothelium, Vascular,
pubmed-meshheading:10553096-Gene Expression Regulation,
pubmed-meshheading:10553096-Humans,
pubmed-meshheading:10553096-Intercellular Adhesion Molecule-1,
pubmed-meshheading:10553096-Intracellular Fluid,
pubmed-meshheading:10553096-NF-kappa B,
pubmed-meshheading:10553096-NF-kappa B p50 Subunit,
pubmed-meshheading:10553096-NFATC Transcription Factors,
pubmed-meshheading:10553096-Nuclear Proteins,
pubmed-meshheading:10553096-Proto-Oncogene Proteins c-rel,
pubmed-meshheading:10553096-Response Elements,
pubmed-meshheading:10553096-Sequence Deletion,
pubmed-meshheading:10553096-Substance P,
pubmed-meshheading:10553096-Transcription Factor AP-1,
pubmed-meshheading:10553096-Transcription Factor RelA,
pubmed-meshheading:10553096-Transcription Factors,
pubmed-meshheading:10553096-Tumor Necrosis Factor-alpha,
pubmed-meshheading:10553096-Vascular Cell Adhesion Molecule-1
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pubmed:year |
1999
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pubmed:articleTitle |
Substance P activates coincident NF-AT- and NF-kappa B-dependent adhesion molecule gene expression in microvascular endothelial cells through intracellular calcium mobilization.
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pubmed:affiliation |
Department of Dermatology, Emory Skin Diseases Research Core Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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