IκB Kinase Is a Critical Regulator of Chemokine Expression and Lung Inflammation in Respiratory Syncytial Virus Infection
| Autor: | Zoran Gatalica, Peter B. Ernst, Helene A. Haeberle, Allan R. Brasier, Sharon Petronella, Antonella Casola, Hans-Juergen Dieterich, Roberto P. Garofalo |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Chemokine
Immunology Respiratory Syncytial Virus Infections IκB kinase Protein Serine-Threonine Kinases Virus Replication Bronchoalveolar Lavage Microbiology Pathogenesis Mice Cell Line Tumor Virology Animals Humans RNA Messenger Chemokine CCL4 Mononegavirales Chemokine CCL5 Lung Macrophage inflammatory protein Chemokine CCL2 Mice Inbred BALB C biology NF-kappa B I-Kappa-B Kinase Pneumonia Macrophage Inflammatory Proteins respiratory system biology.organism_classification NFKB1 I-kappa B Kinase Interleukin-10 Respiratory Syncytial Viruses IκBα Insect Science biology.protein Pathogenesis and Immunity Female Chemokines Peptides |
| Zdroj: | Journal of Virology. 78:2232-2241 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.78.5.2232-2241.2004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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