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.
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Acknowledgements
We thank Karen Kwon for technical assistance and Yang Shi (Harvard Medical School, Boston, MA) for providing pBS/U6. This work was funded by operating grants from the Canadian Cystic Fibrosis Foundation (to Jim HU), an operating grant from the Foundation Fighting Blindness-Canada (To Jim HU) and operating grants from the Canadian Institutes of Health Research (to Jim HU and A. Keith TANAWELL). and Jim HU is a CCFF Scholar and holds a Premier's Research Excellence Award of Ontario Canada.
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CAO, H., WANG, A., MARTIN, B. et al. Down-regulation of IL-8 expression in human airway epithelial cells through helper-dependent adenoviral-mediated RNA interference. Cell Res 15, 111–119 (2005). https://doi.org/10.1038/sj.cr.7290275
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DOI: https://doi.org/10.1038/sj.cr.7290275
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