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J Immunol. 1998 Jul 15;161(2):1007-16.

Respiratory syncytial virus-induced RANTES production from human bronchial epithelial cells is dependent on nuclear factor-kappa B nuclear binding and is inhibited by adenovirus-mediated expression of inhibitor of kappa B alpha.

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1
Department of Infectious Diseases, Imperial College School of Medicine (Hammersmith Campus), London, United Kingdom.

Abstract

Respiratory syncytial virus (RSV) infection is an important cause of lower respiratory tract illness, the severity of which may be partly due to cellular recruitment. RSV infection activates chemokine secretion from airway epithelial cells by largely unknown mechanisms. We investigated the regulation of RSV-induced activation of the chemokine RANTES in the bronchial epithelial cell line BEAS-2B and primary normal human tracheobronchial epithelial cultures. RANTES protein and mRNA were detected at 24 h and up until 72 h from cultures of BEAS-2B infected with replicating virus, but not with UV-inactivated RSV. RSV infection of BEAS-2B or normal human tracheobronchial epithelial cells stimulated NF-kappa B translocation to the nucleus and binding to the RANTES-specific kappa B-binding sequences within 2 h, with levels peaking at 24 h. Supershift assays indicated that binding was due to p50/p65 heterodimers. BEAS-2B cells were transfected with a replication-deficient adenoviral vector, expressing a mutated, nondegradable form of I kappa B alpha. I kappa B alpha overexpression specifically blocked NF-kappa B translocation and inhibited mRNA accumulation and secretion of RANTES induced by RSV or TNF-alpha plus IFN-gamma. Adenoviral transfection did not interfere with RSV replication or significantly induce apoptosis. Further, a control adenovirus, expressing the beta-galactosidase gene, did not alter cellular functions. Thus, NF-kappa B nuclear translocation is a critical step in RSV induction of RANTES secretion. Elucidating the mechanisms of cellular activation by RSV and targeting specific areas may lead to novel therapeutic approaches in the treatment of RSV.

PMID:
9670982
[Indexed for MEDLINE]
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