rdf:type |
|
lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0022567,
umls-concept:C0037083,
umls-concept:C0038170,
umls-concept:C0185117,
umls-concept:C0521447,
umls-concept:C0871261,
umls-concept:C1123023,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2604787,
umls-concept:C2911684,
umls-concept:C2911692
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pubmed:issue |
12
|
pubmed:dateCreated |
2006-11-22
|
pubmed:abstractText |
The human beta-defensin 3 (hBD-3) is an inducible epithelial peptide antibiotic that has potent antistaphylococcal activity. Infection of skin epithelial cells with viable Staphylococcus aureus, a common skin pathogen, induces increased gene expression of hBD-3 and other antimicrobial peptides. The aim of this study was to identify signaling pathways and nuclear responses that contribute to the gene expression of hBD-3 in primary human keratinocytes upon contact with S. aureus. Increased hBD-3 peptide was observed by immunofluorescence microscopy in keratinocytes exposed to S. aureus and to lipoteichoic acid (LTA). Both are ligands for the cell surface Toll-like receptor 2 (TLR2), and thus the contribution of TLR2 signaling in hBD-3 expression was examined. Functional inhibition of TLR2 prior to S. aureus stimulation significantly decreased hBD-3 mRNA levels by 37%, attesting to the involvement of this surface receptor in the initial recognition and downstream signaling for hBD-3 expression. Treatment of keratinocytes with a p38 mitogen-activated protein kinase (MAPK) inhibitor prior to either S. aureus or LTA stimulation was associated with reduced hBD-3 mRNA transcripts and peptide. We also propose a role for the MAPK-regulated transcriptional activating protein 1 in S. aureus-induced hBD-3 gene expression. Combined, these studies indicate a role for TLR2 signaling and MAPK activation in the upregulation of hBD-3 and demonstrate the innate immune capacity of skin keratinocytes under conditions of S. aureus challenge to enhance the local expression of this antistaphylococcal peptide antibiotic.
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pubmed:grant |
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-10768988,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-10837369,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-10882713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-11085990,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-11157059,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-11223260,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-11702237,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-11719807,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-12072060,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-12374875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-12514169,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-12594207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-12819054,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-12949495,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-12960356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-14662888,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-14688115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-15494486,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-15829297,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-15845503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-15963694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-15982297,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-16041048,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-16319062,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-2668334,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16954397-8912180
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Teichoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Defensins,
http://linkedlifedata.com/resource/pubmed/chemical/beta-defensin 3, human,
http://linkedlifedata.com/resource/pubmed/chemical/lipoteichoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0019-9567
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
74
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6847-54
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16954397-Cells, Cultured,
pubmed-meshheading:16954397-Gene Expression,
pubmed-meshheading:16954397-Humans,
pubmed-meshheading:16954397-Keratinocytes,
pubmed-meshheading:16954397-Lipopolysaccharides,
pubmed-meshheading:16954397-RNA, Messenger,
pubmed-meshheading:16954397-Signal Transduction,
pubmed-meshheading:16954397-Skin,
pubmed-meshheading:16954397-Staphylococcus aureus,
pubmed-meshheading:16954397-Teichoic Acids,
pubmed-meshheading:16954397-Toll-Like Receptor 2,
pubmed-meshheading:16954397-Transcription, Genetic,
pubmed-meshheading:16954397-Transcription Factor AP-1,
pubmed-meshheading:16954397-beta-Defensins,
pubmed-meshheading:16954397-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2006
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pubmed:articleTitle |
Signal transduction and nuclear responses in Staphylococcus aureus-induced expression of human beta-defensin 3 in skin keratinocytes.
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pubmed:affiliation |
Department of Veterans Affairs S-111-ID, Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108, USA. bmenzies@u.washington.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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