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

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...

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Veröffentlicht in:Cell research 2005-02, Vol.15 (2), p.111-119
Hauptverfasser: CAO, Huibi, WANG, Anan, MARTIN, Bernard, KOEHLER, David R, ZEITLIN, Pamela L, TANAWELL, A Keith, HU, Jim
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Sprache:eng
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Zusammenfassung: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.
ISSN:1001-0602
1748-7838
DOI:10.1038/sj.cr.7290275