Linked Life Data

16954397

Source:http://linkedlifedata.com/resource/pubmed/id/16954397

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pubmed-article:16954397pubmed:abstractTextThe 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.lld:pubmed
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pubmed-article:16954397pubmed:authorpubmed-author:MenziesBarbar...lld:pubmed
pubmed-article:16954397pubmed:authorpubmed-author:KenoyerAimeeAlld:pubmed
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pubmed-article:16954397pubmed:dateRevised2009-11-19lld:pubmed
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pubmed-article:16954397pubmed:articleTitleSignal transduction and nuclear responses in Staphylococcus aureus-induced expression of human beta-defensin 3 in skin keratinocytes.lld:pubmed
pubmed-article:16954397pubmed:affiliationDepartment of Veterans Affairs S-111-ID, Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108, USA. bmenzies@u.washington.edulld:pubmed
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pubmed-article:16954397pubmed:publicationTypeResearch Support, U.S. Gov't, Non-P.H.S.lld:pubmed
pubmed-article:16954397pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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