Down-regulation of IL-8 expression in human airway epithelial cells through helper-dependent adenoviral-mediated RNA interference

Huibi Cao, Anan Wang, Bernard Martin, David R. Koehler, Pamela L. Zeitlin, A. Keith Tanawell, Jim Hu

Research output: Contribution to journalArticle

Abstract

Interleukin (IL)-8 is a potent neutrophil chemotactic factor and a crucial mediator in neutrophil-dependent inflammation. Various cell types produce IL-8, either in response to external stimuli such as cytokines or bacterial infection, or after malignant transformation. Anti-IL-8 strategies have been considered for anti-inflammatory therapy. In this paper we demonstrate that the RNA interference technique can be used to efficiently down-regulate IL-8 protein expression in airway epithelial cells. We used a helper-dependent adenoviral vector to express a small hairpin (sh)RNA targeting human IL-8 in cultured airway epithelial cells (IB3-1, Cftr-/-; C38, Cftr-corrected) stimulated with TNF-α, IL-1β or heat-inactivated Burkholderia cenocepacia. Stimulated IL-8 expression in IB3-1 and C38 cells was significantly reduced by shRNA expression. The shRNA targeting IL-8 had no effect on the activation of NF-κB, or on the protein levels of IκB or IL-6, suggesting that this anti-IL-8 strategy was highly specific, and therefore may offer potential for the treatment of inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalCell Research
Volume15
Issue number2
DOIs
StatePublished - 2005

Keywords

  • Chemokine
  • Cystic fibrosis
  • Helper-dependent adenoviral vector
  • Inflammation
  • Interleukin-8
  • Neutrophil
  • RNA interference

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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