Signal transduction and nuclear responses in Staphylococcus aureus-induced expression of human β-defensin 3 in skin keratinocytes

Barbara Menzies, Aimee Kenoyer

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The human β-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.

Original languageEnglish (US)
Pages (from-to)6847-6854
Number of pages8
JournalInfection and Immunity
Volume74
Issue number12
DOIs
StatePublished - Dec 1 2006

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Defensins
Keratinocytes
Staphylococcus aureus
Signal Transduction
Toll-Like Receptor 2
Skin
Peptides
Mitogen-Activated Protein Kinases
Gene Expression
Anti-Bacterial Agents
Messenger RNA
p38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Fluorescence Microscopy
Up-Regulation
Epithelial Cells
Ligands
Infection

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Signal transduction and nuclear responses in Staphylococcus aureus-induced expression of human β-defensin 3 in skin keratinocytes. / Menzies, Barbara; Kenoyer, Aimee.

In: Infection and Immunity, Vol. 74, No. 12, 01.12.2006, p. 6847-6854.

Research output: Contribution to journalArticle

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