High Susceptibility for Cystic Fibrosis Human Airway Gland Cells to Produce IL-8 Through the IκB Kinase α Pathway in Response to Extracellular NaCl Content - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2023

High Susceptibility for Cystic Fibrosis Human Airway Gland Cells to Produce IL-8 Through the IκB Kinase α Pathway in Response to Extracellular NaCl Content

Sandie Escotte
  • Fonction : Auteur
Jean Paul Couetil
  • Fonction : Auteur
Dominique Hubert
  • Fonction : Auteur
Daniel Dusser
  • Fonction : Auteur
Edith Puchelle
  • Fonction : Auteur
Jacky Jacquot
  • Fonction : Auteur

Résumé

Abstract Increasing evidence suggests that in airways from cystic fibrosis (CF) patients, inflammation may precede bacterial infection and be related to an endogenous dysregulation of proinflammatory cytokines in airway epithelial cells. Several investigators have reported that, in CF airway fluids, elevated NaCl concentrations may also contribute to the diseased state by inhibiting the bactericidal properties of airway fluid. Because many proinflammatory cytokines are transcriptionally regulated by the NF-κB, we investigated whether an elevated extracellular NaCl content in airway fluids significantly impaired the regulation of the NF-κB/IκBα complex and the chemokine IL-8 production in primary non-CF and CF human bronchial gland epithelial cells. Exposure of non-CF gland cells to hypotonic (85 mM) NaCl solution, compared with isotonic (115 mM) NaCl and hypertonic (170 mM) NaCl solutions, resulted in a significant decrease in IL-8 production that was paralleled by a strong inhibition of activated NF-κB associated with an increased cytosolic expression of IκBα and a decrease in the IκB kinase α protein level. In CF gland cells, we demonstrated that, compared with the high IL-8 in an hypertonic solution, the release of IL-8 was significantly reduced 2-fold in an isotonic solution and 5-fold in a hypotonic solution. Strikingly, exposure of CF bronchial gland cells to either hypotonic or isotonic milieu did not result in a marked inhibition of the activated NF-κB/IκBα system. This is the first demonstration that primary human CF bronchial gland cells exhibit abnormally high IL-8 production through constitutively activated NF-κB and high IκB kinase α level, whatever the hypo-, iso-, and hypertonic NaCl milieu.
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Dates et versions

hal-03953414 , version 1 (24-01-2023)

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Olivier Tabary, Sandie Escotte, Jean Paul Couetil, Dominique Hubert, Daniel Dusser, et al.. High Susceptibility for Cystic Fibrosis Human Airway Gland Cells to Produce IL-8 Through the IκB Kinase α Pathway in Response to Extracellular NaCl Content. Journal of Immunology, 2023, 164 (6), pp.3377 - 3384. ⟨10.4049/jimmunol.164.6.3377⟩. ⟨hal-03953414⟩

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