IκB Kinase Is a Critical Regulator of Chemokine Expression and Lung Inflammation in Respiratory Syncytial Virus Infection

Helene A. Haeberle, Antonella Casola, Zoran Gatalica, Sharon Croisant, Hans Juergen Dieterich, Peter B. Ernst, Allan R. Brasier, Roberto Garofalo

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Respiratory syncytial virus (RSV) is the major etiologic agent of severe epidemic lower respiratory tract infections in infancy. Airway mucosal inflammation plays a critical role in the pathogenesis of RSV disease in both natural and experimental infections. RSV is among the most potent biological stimuli that induce the expression of inflammatory genes, including those encoding chemokines, but the mechanism(s) that controls virus-mediated airway inflammation in vivo has not been fully elucidated. Herein we show that the inoculation of BALB/c mice with RSV results in rapid activation of the multisubunit IκB kinase (IKK) in lung tissue. IKK transduces upstream activating signals into the rate-limiting phosphorylation (and proteolytic degradation) of IκBα, the inhibitory subunit that under normal conditions binds to the nuclear factor (NF)-κB complex and keeps it in an inactive cytoplasmic form. Mice treated intranasally with interleukin-10 or with a specific cell-permeable peptide that blocks the association of the catalytic subunit IKKβ with the regulatory protein NEMO showed a striking reduction of lung NF-κB DNA binding activity, chemokine gene expression, and airway inflammation in response to RSV infection. These findings suggest that IKKβ may be a potential target for the treatment of acute or chronic inflammatory diseases of the lung.

Original languageEnglish (US)
Pages (from-to)2232-2241
Number of pages10
JournalJournal of Virology
Volume78
Issue number5
DOIs
StatePublished - Mar 2004

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IKappaB kinase
Respiratory Syncytial Virus Infections
Respiratory Syncytial Viruses
chemokines
Chemokines
Pneumonia
phosphotransferases (kinases)
Phosphotransferases
inflammation
lungs
viruses
Inflammation
infection
Lung
Gene Expression
respiratory tract diseases
Virus Diseases
B-DNA
Respiratory Tract Infections
Interleukin-10

ASJC Scopus subject areas

  • Immunology

Cite this

IκB Kinase Is a Critical Regulator of Chemokine Expression and Lung Inflammation in Respiratory Syncytial Virus Infection. / Haeberle, Helene A.; Casola, Antonella; Gatalica, Zoran; Croisant, Sharon; Dieterich, Hans Juergen; Ernst, Peter B.; Brasier, Allan R.; Garofalo, Roberto.

In: Journal of Virology, Vol. 78, No. 5, 03.2004, p. 2232-2241.

Research output: Contribution to journalArticle

Haeberle, Helene A. ; Casola, Antonella ; Gatalica, Zoran ; Croisant, Sharon ; Dieterich, Hans Juergen ; Ernst, Peter B. ; Brasier, Allan R. ; Garofalo, Roberto. / IκB Kinase Is a Critical Regulator of Chemokine Expression and Lung Inflammation in Respiratory Syncytial Virus Infection. In: Journal of Virology. 2004 ; Vol. 78, No. 5. pp. 2232-2241.
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