Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli

Jürgen Schauber, Robert A. Dorschner, Kenshi Yamasaki, Brook Brouha, Richard L. Gallo

Research output: Contribution to journalArticle

195 Citations (Scopus)

Abstract

Immune defence against microbes depends in part on the production of antimicrobial peptides, a process that occurs in a variety of cell types but is incompletely understood. In this study, the mechanisms responsible for the induction of cathelicidin and β-defensin antimicrobial peptides were found to be independent and specific to the cell type and stimulus. Vitamin D 3 induced cathelicidin expression in keratinocytes and monocytes but not in colonic epithelial cells. Conversely, butyrate induced cathelicidin in colonic epithelia but not in keratinocytes or monocytes. Distinct factors induced β-defensin expression. In all cell types, vitamin D3 activated the cathelicidin promoter and was dependent on a functional vitamin D responsive element. However, in colonic epithelia butyrate induced cathelicidin expression without increasing promoter activity and vitamin D3 activated the cathelicidin promoter without a subsequent increase in transcript accumulation. Induction of cathelicidin transcript correlated with increased processed mature peptide and enhanced antimicrobial activity against Staphylococcus aureus. However, induction of β-defensin-2 expression did not alter the innate antimicrobial capacity of cells in culture. These data suggest that antimicrobial peptide expression is regulated in a tissue-specific manner at transcriptional, post-transcriptional and post-translational levels. Furthermore, these data show for the first time that innate antimicrobial activity can be triggered independently of the release of other pro-inflammatory molecules, and suggest strategies for augmenting innate immune defence without increasing inflammation.

Original languageEnglish
Pages (from-to)509-519
Number of pages11
JournalImmunology
Volume118
Issue number4
DOIs
Publication statusPublished - 2006 Aug 1
Externally publishedYes

Keywords

  • Cathelicidin
  • Colon mucosa
  • Defensin
  • Gene regulation
  • Human
  • Skin

ASJC Scopus subject areas

  • Immunology

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