β-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells

Puja Vora, Adrienne Youdim, Lisa S. Thomas, Masayuki Fukata, Samuel Y. Tesfay, Katie Lukasek, Kathrin S. Michelsen, Akihiro Wada, Toshiya Hirayama, Moshe Arditi, Maria T. Abreu

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267 Scopus citations

Abstract

The intestinal epithelium serves as a barrier to the intestinal flora. In response to pathogens, intestinal epithelial cells (IEC) secrete proinflammatory cytokines. To aid in defense against bacteria, IEC also secrete antimicrobial peptides, termed defensins. The aim of our studies was to understand the role of TLR-signaling in regulation of β-defensin expression by IEC. The effect of LPS and peptidoglycan on β-defensin-2 expression was examined in IEC lines constitutively or transgenically expressing TLRs. Regulation of β-defensin-2 was assessed using promoter-reporter constructs of the human β-defensin-2 gene. LPS and peptidoglycan stimulated β-defensin-2 promoter activation in a TLR4- and TLR2-dependent manner, respectively. A mutation in the NF-κB or AP-1 site within the β-defensin-2 promoter abrogated this response. In addition, inhibition of Jun kinase prevents up-regulation of β-defensin-2 protein expression in response to LPS. IEC respond to pathogen-associated molecular patterns with expression of the antimicrobial peptide β-defensin-2. This mechanism may protect the intestinal epithelium from pathogen invasion and from potential invaders among the commensal flora.

Original languageEnglish (US)
Pages (from-to)5398-5405
Number of pages8
JournalJournal of Immunology
Volume173
Issue number9
StatePublished - Nov 1 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Vora, P., Youdim, A., Thomas, L. S., Fukata, M., Tesfay, S. Y., Lukasek, K., Michelsen, K. S., Wada, A., Hirayama, T., Arditi, M., & Abreu, M. T. (2004). β-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. Journal of Immunology, 173(9), 5398-5405.