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 [10.1074/jbc.M413726200].

The I kappa B kinase is a key factor in triggering influenza A virus-induced inflammatory cytokine production in airway epithelial cells

AMICI, CARLA;LA FRAZIA, SIMONE;SANTORO, MARIA GABRIELLA
2005-01-01

Abstract

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.
2005
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Con Impact Factor ISI
Cells; Cytology; Enzymes; Epidemiology; Molecular biology; Pathology; Epithelial cells; Influenza; Overabundant production; Proinflammatory cytokines; Viruses; cytokine; delta12 prostaglandin J2; I kappa B kinase; immunoglobulin enhancer binding protein; interleukin 8; autacoid; CHUK protein, human; IKBKB protein, human; IKBKE protein, human; primer DNA; protein serine threonine kinase; article; cell specificity; controlled study; cytokine production; enzyme activation; enzyme activity; enzyme inhibition; epithelium cell; human; human cell; inflammation; influenza; Influenza virus A; lung alveolus epithelium; priority journal; protein expression; respiratory epithelium; virus infection; animal; biosynthesis; cell line; cytology; dog; gel mobility shift assay; lung; metabolism; nucleotide sequence; virology; Influenza A virus; Influenza virus; Animals; Base Sequence; Cell Line; DNA Primers; Dogs; Electrophoretic Mobility Shift Assay; Humans; I-kappa B Kinase; Inflammation Mediators; Influenza A virus; Interleukin-8; Lung; NF-kappa B; Protein-Serine-Threonine Kinases
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 [10.1074/jbc.M413726200].
Bernasconi, D; Amici, C; LA FRAZIA, S; Ianaro, A; Santoro, Mg
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/38034
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