Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
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.
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
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0019-9567
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6847-54
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Signal transduction and nuclear responses in Staphylococcus aureus-induced expression of human beta-defensin 3 in skin keratinocytes.
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
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural