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(American Journal of Pathology. 2003;162:293-302.)
© 2003 American Society for Investigative Pathology

Regular Articles

Interleukin-10 Inhibits Elevated Chemokine Interleukin-8 and Regulated on Activation Normal T Cell Expressed and Secreted Production in Cystic Fibrosis Bronchial Epithelial Cells by Targeting the I_kB Kinase /ß Complex

Olivier Tabary^*, Céline Muselet^*, Sandie Escotte^*, Frank Antonicelli, Dominique Hubert, Daniel Dusser and Jacky Jacquot^*

From INSERM U514,^* IFR 53, Reims; INSERM E213, Hôpital Trousseau, Paris; Laboratoire de Biochimie, Centre National de la Recherché Scientifique, FRE 2260, IFR 53, Reims; and Service de Pneumologie, Hôpital Cochin, Paris, France

Accumulating evidence suggests that in cystic fibrosis (CF) patients, airway fluids are characterized by decreased antibacterial activity, elevated NaCl concentration, and high levels of chemokines, resulting in exaggerated activation of the transcriptional nuclear factor (NF)-B in airway epithelial cells. The present study was undertaken to evaluate the effects of anti-inflammatory cytokine interleukin-10 (IL-10) on NaCl-induced chemokine IL-8 and regulated on activation normal T cell expressed and secreted (RANTES) expression through the NF-B signaling in primary F508 CF and non-CF (control) human bronchial epithelial cells. Exposure of CF and non-CF bronchial epithelial cells to hypertonic (170 mmol/L NaCl) milieu compared to isotonic (115 mmol/L NaCl) and hypotonic (85 mmol/L NaCl) milieu caused a significant, NaCl-dependent increase in IL-8 and RANTES gene expression and protein production. Compared to non-CF cells, CF bronchial epithelial cells were characterized by a higher susceptibility to produce elevated IL-8 and RANTES production in an hypertonic NaCl milieu in response to IL-1ß activation. Treatment with IL-10 suppressed IL-8 and RANTES gene expression in both non-CF and CF bronchial epithelial cells was associated with a reduced expression of I_kB (IKK) /ß kinases, particularly for IKK which is greater expressed in CF bronchial epithelial cells, and resulting in reduced NF-B activation. These findings suggest that IL-10 might have anti-inflammatory benefits in airways of CF patients.

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