Influenza A viruses continue to represent a severe threat worldwide, causing large epidemics and pandemics responsible for thousands of deaths every year. Excessive inflammation due to overabundant production of proinflammatory cytokines by airway epithelial cells is considered an important factor in disease pathogenesis. Here we report that influenza A virus induced I kappa B kinase (IKK) activity in human airway epithelial A549 cells, resulting in persistent activation of nuclear factor-kappa B (NF-kappa B), a critical regulator of the inflammatory response. Although lung epithelial cells are highly sensitive to stimulation of the IKK/NF-kappa B pathway by influenza virus infection, NF-kappa B was not activated in several non-pulmonary cells permissive to the virus, indicating a cell-specific response. Moreover, NF-kappa B was not essential for virus replication but triggered the expression of proinflammatory cytokines in infected lung cells and was directly responsible for production of high levels of interleukin-8, a chemokine associated with influenza-induced inflammation and airway pathology. We also report that 9-deoxy-Delta(9), Delta(12)-13,14-dihydro-prostaglandin D-2, a cyclopentenone prostanoid with therapeutic efficacy against influenza in preclinical studies, was a powerful inhibitor of influenza virus-induced IKK activity and interleukin-8 production by human pulmonary cells. The results identify IKK as an important factor in triggering influenza virus-induced inflammatory reactions in pulmonary epithelium, suggesting novel therapeutic approaches in the treatment of influenza.
Bernasconi, D., Amici, C., La Frazia, S., Ianaro, A., & Santoro, M.G. (2005). The I kappa B kinase is a key factor in triggering influenza A virus-induced inflammatory cytokine production in airway epithelial cells. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 280(25), 24127-24134.
|Tipologia:||Articolo su rivista|
|Citazione:||Bernasconi, D., Amici, C., La Frazia, S., Ianaro, A., & Santoro, M.G. (2005). The I kappa B kinase is a key factor in triggering influenza A virus-induced inflammatory cytokine production in airway epithelial cells. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 280(25), 24127-24134.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1074/jbc.M413726200|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2005|
|Titolo:||The I kappa B kinase is a key factor in triggering influenza A virus-induced inflammatory cytokine production in airway epithelial cells|
|Autori:||Bernasconi, D ; Amici, C ; La Frazia, S ; Ianaro, A ; Santoro, MG|
|Appare nelle tipologie:||01 - Articolo su rivista|