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

Journal Article · Fri Sep 30 00:00:00 EDT 2011 · Virology

DOI:https://doi.org/10.1016/j.virol.2011.07.007· OSTI ID:21587891

Dey, Nilay; Tianshuang, Liu ^[1]; Garofalo, Roberto P ^[1]; Casola, Antonella ^[1]

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1. Department of Pediatrics, University of Texas Medical Branch, Galveston, TX (United States)

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.

• OSTI ID: 21587891
• Journal Information: Virology, Vol. 418, 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); ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

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