Ikkepsilon regulates viral-induced interferon regulatory factor-3 activation via a redox-sensitive pathway
- Department of Pediatrics, University of Texas Medical Branch, Galveston, TX (United States)
- Millennium Pharmaceuticals Inc, Cambridge, MA (United States)
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX (United States)
- Department of Pediatrics, University of Texas Medical Branch, Galveston, TX (United States) and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX (United States) and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX (United States)
Respiratory syncytial virus (RSV)-induced chemokine gene expression occurs through the activation of a subset of transcription factors, including Interferon Regulatory Factor (IRF)-3. In this study, we have investigated the signaling pathway leading to RSV-induced IRF-3 activation and whether it is mediated by intracellular reactive oxygen species (ROS) generation. Our results show that RSV infection induces expression and catalytic activity of IKK{epsilon}, a noncanonical IKK-like kinase. Expression of a kinase-inactive IKK{epsilon} blocks RSV-induced IRF-3 serine phosphorylation, nuclear translocation and DNA-binding, leading to inhibition of RANTES gene transcription, mRNA expression and protein synthesis. Treatment of alveolar epithelial cells with antioxidants or with NAD(P)H oxidase inhibitors abrogates RSV-induced chemokine secretion, IRF-3 phosphorylation and IKK{epsilon} induction, indicating that ROS generation plays a fundamental role in the signaling pathway leading to IRF-3 activation, therefore, identifying a novel molecular target for the development of strategies aimed to modify the inflammatory response associated with RSV infection of the lung.
- OSTI ID:
- 20850561
- Journal Information:
- Virology, Vol. 353, Issue 1; Other Information: DOI: 10.1016/j.virol.2006.05.022; PII: S0042-6822(06)00341-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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