Low concentrations of LL-37 alter IL-8 production by keratinocytes and bronchial epithelial cells in response to proinflammatory stimuli

Niall C.J. Filewod, Jelena Pistolic, Robert E.W. Hancock

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The immunomodulatory cationic host defence peptide LL-37 plays an important role in epithelial innate immunity; at higher concentrations (20-50 μg mL-1) associated with inflammation, LL-37 elicits the production of cytokines and chemokines. It was demonstrated here that lower, physiologically relevant LL-37 concentrations (2-3 μg mL-1) altered epithelial cell responses to proinflammatory stimuli. In combination with interleukin-1β (IL-1β) and the Toll-like receptor-5 (TLR5) agonist flagellin, these low concentrations of LL-37 synergistically increased IL-8 production by both proliferating and differentiated keratinocytes and by bronchial epithelial cells. In combination with the TLR2/1 agonist PAM3CSK4, LL-37 synergistically induced transcription and the release of both IL-8 and IL-6 from primary bronchial epithelial cells; the IL-8 response was demonstrated to be regulated by epidermal growth factor receptor signalling. Treatment of bronchial epithelial cells with LL-37 and the TLR3 agonist polyI:C resulted in synergistic increases in IL-8 release and cytotoxicity. These data indicate that low concentrations of LL-37 may alter epithelial responses to infecting microorganisms in vivo.

Original languageEnglish
Pages (from-to)233-240
Number of pages8
JournalFEMS Immunology and Medical Microbiology
Volume56
Issue number3
DOIs
Publication statusPublished - 1 Aug 2009

Keywords

  • IL-8
  • Inflammation
  • LL-37
  • Lung
  • Skin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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