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Title: TAK1 regulates NF-{Kappa}B and AP-1 activation in airway epithelial cells following RSV infection

Abstract

Respiratory syncytial virus (RSV) is the most common cause of epidemic respiratory diseases in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B) and AP-1. In this study, we have investigated the signaling pathway leading to activation of these two transcription factors in response to RSV infection. Our results show that IKK{beta} plays a key role in viral-induced NF-{kappa}B activation, while JNK regulates AP-1-dependent gene transcription, as demonstrated by using kinase inactive proteins and chemical inhibitors of the two kinases. Inhibition of TAK1 activation, by overexpression of kinase inactive TAK1 or using cells lacking TAK1 expression, significantly reduced RSV-induced NF-{kappa}B and AP-1 nuclear translocation and DNA-binding activity, as well as NF-{kappa}B-dependent gene expression, identifying TAK1 as an important upstream signaling molecule regulating RSV-induced NF-{kappa}B and AP-1 activation. - Highlights: > IKK{beta} is a major kinase involved in RSV-induced NF-{kappa}B activation. > JNK regulates AP-1-dependent gene transcription in RSV infection. > TAK1 is a critical upstream signaling molecule for both pathways in infected cells.

Authors:
;  [1];  [1];  [2];  [2];  [1];  [2];  [2]
  1. Department of Pediatrics, University of Texas Medical Branch, Galveston, TX (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
21587891
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 418; Journal Issue: 2; Other Information: DOI: 10.1016/j.virol.2011.07.007; PII: S0042-6822(11)00301-1; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DISEASES; DNA; GENES; INFANTS; INFLAMMATION; PHOSPHOTRANSFERASES; TRANSCRIPTION; TRANSCRIPTION FACTORS; VIRUSES; AGE GROUPS; ANIMALS; CHILDREN; ENZYMES; MAMMALS; MAN; MICROORGANISMS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; PARASITES; PATHOLOGICAL CHANGES; PHOSPHORUS-GROUP TRANSFERASES; PRIMATES; PROTEINS; SYMPTOMS; TRANSFERASES; VERTEBRATES

Citation Formats

Dey, Nilay, Liu Tianshuang, Garofalo, Roberto P., Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, Department of Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, Casola, Antonella, E-mail: ancasola@utmb.edu, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, and Department of Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX. TAK1 regulates NF-{Kappa}B and AP-1 activation in airway epithelial cells following RSV infection. United States: N. p., 2011. Web. doi:10.1016/j.virol.2011.07.007.
Dey, Nilay, Liu Tianshuang, Garofalo, Roberto P., Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, Department of Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, Casola, Antonella, E-mail: ancasola@utmb.edu, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, & Department of Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX. TAK1 regulates NF-{Kappa}B and AP-1 activation in airway epithelial cells following RSV infection. United States. doi:10.1016/j.virol.2011.07.007.
Dey, Nilay, Liu Tianshuang, Garofalo, Roberto P., Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, Department of Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, Casola, Antonella, E-mail: ancasola@utmb.edu, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, and Department of Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX. Fri . "TAK1 regulates NF-{Kappa}B and AP-1 activation in airway epithelial cells following RSV infection". United States. doi:10.1016/j.virol.2011.07.007.
@article{osti_21587891,
title = {TAK1 regulates NF-{Kappa}B and AP-1 activation in airway epithelial cells following RSV infection},
author = {Dey, Nilay and Liu Tianshuang and Garofalo, Roberto P. and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX and Department of Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX and Casola, Antonella, E-mail: ancasola@utmb.edu and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX and Department of Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX},
abstractNote = {Respiratory syncytial virus (RSV) is the most common cause of epidemic respiratory diseases in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B) and AP-1. In this study, we have investigated the signaling pathway leading to activation of these two transcription factors in response to RSV infection. Our results show that IKK{beta} plays a key role in viral-induced NF-{kappa}B activation, while JNK regulates AP-1-dependent gene transcription, as demonstrated by using kinase inactive proteins and chemical inhibitors of the two kinases. Inhibition of TAK1 activation, by overexpression of kinase inactive TAK1 or using cells lacking TAK1 expression, significantly reduced RSV-induced NF-{kappa}B and AP-1 nuclear translocation and DNA-binding activity, as well as NF-{kappa}B-dependent gene expression, identifying TAK1 as an important upstream signaling molecule regulating RSV-induced NF-{kappa}B and AP-1 activation. - Highlights: > IKK{beta} is a major kinase involved in RSV-induced NF-{kappa}B activation. > JNK regulates AP-1-dependent gene transcription in RSV infection. > TAK1 is a critical upstream signaling molecule for both pathways in infected cells.},
doi = {10.1016/j.virol.2011.07.007},
journal = {Virology},
issn = {0042-6822},
number = 2,
volume = 418,
place = {United States},
year = {2011},
month = {9}
}