Relationship between IkappaBalpha deficiency, NFkappaB activity and interleukin-8 production in CF human airway epithelial cells
| Autor: | Tabary, O., Escotte, S., Couetil, J. P., Hubert, D., Dusser, D., Puchelle, E., Jacquot, J. |
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| Přispěvatelé: | Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA) - IFR53 - Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Chirurgie Cardio-Vasculaire (DCCV), Hôpital Broussais, Service de pneumologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP], Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Birembaut, Philippe |
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Cystic Fibrosis
MESH: Cystic Fibrosis MESH: I-kappa B Proteins MESH: NF-kappa B Bronchi MESH: Genistein Respiratory Mucosa MESH: Protein-Tyrosine Kinases [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract Cytosol NF-KappaB Inhibitor alpha MESH: Cytosol MESH: Respiratory Mucosa Humans Pseudomonas Infections Enzyme Inhibitors Cells Cultured MESH: Humans Interleukin-8 NF-kappa B MESH: Pseudomonas Infections MESH: Bronchi Protein-Tyrosine Kinases respiratory system Genistein MESH: Interleukin-8 DNA-Binding Proteins MESH: Enzyme Inhibitors [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract I-kappa B Proteins MESH: DNA-Binding Proteins MESH: Cells Cultured |
| Zdroj: | Archiv für die Gesammte Physiologie des Menschen und der Thiere Archiv für die Gesammte Physiologie des Menschen und der Thiere, 2001, 443 Suppl 1, pp.S40-4. 〈10.1007/s004240100642〉 Archiv für die Gesammte Physiologie des Menschen und der Thiere, 2001, 443 Suppl 1, pp.S40-4. ⟨10.1007/s004240100642⟩ |
| DOI: | 10.1007/s004240100642〉 |
| Popis: | Several recent reports have suggested that airway inflammation may precede infection and relate to an endogenous dysregulation of pro-inflammatory cytokines in cystic fibrosis (CF) airways. Evidence suggests that activation of the nuclear factor kappa B (NFkappaB), which regulates the inflammatory gene transcription, depends on the degradation of the inhibitory factor IkappaBalpha. We show that, in in situ human DeltaF508 CF bronchial tissues, inhibitor factor IkappaBalpha is not present in gland cells, although endogenous levels of chemokine IL-8 are high. These data are confirmed by studying cultured CF human bronchial gland cells, in which a lack of cytosolic IkappaBalpha and high levels of activated NFkappaB, concomitant with IL-8 overproduction (a 13-fold increase) are found when compared to non-CF bronchial gland cells. Interestingly, treatment of CF gland cells with the isoflavone genistein, a well known CFTR mutant Cl(-) channel stimulator, results in a significant decrease ( P < 0.001) in IL-8 production down to levels released by non-CF gland cells. The addition of genistein also reverses the effects of lipopolysaccharide (LPS) Pseudomonas-aeruginosa-induced nuclear translocation of NFkappaB by increasing IkappaBalpha protein level (65%) in CF gland cells. Our data indicate that the induction of IkappaBalpha protein in CF airway glandular epithelial cells may be a novel mechanism by which IL-8-mediated lung inflammatory events are markedly reduced in CF patients, at least at the airway glandular level. |
| Databáze: | OpenAIRE |
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