Volume 15, No 2, Feb 2005
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 15 Issue 2, February 2005: 111-119
ORIGINAL ARTICLES
Down-regulation of IL-8 expression in human airway epithelial cells through helper-dependent adenoviral-mediated RNA interference
Huibi CAO1,4, Anan WANG1, Bernard MARTIN1, David R. KOEHLER1,4, Pamela L. ZEITLIN5, A. Keith TANAWELL1,2,3, Jim HU1,2,4,*
1Programme in Lung Biology Research and the Canadian Institutes of Health Research Group in Lung Development, Hospital for Sick Children, Toronto, Canada M5G 1X8.
2Department of Paediatrics, University of Toronto, Toronto, Canada M5S 1A1
3Department of Physiology, University of Toronto, Toronto, Canada M5S 1A1
4Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada M5S 1A1
5Departments of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Correspondence: Jim HU(jhu@sickkids.on.ca)
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 IkB or IL-6, suggesting that this anti-IL-8 strategy was highly specific, and therefore may offer potential for the treatment of inflammatory diseases.
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