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Fluticasone reduces IL-6 and IL-8 production of cystic fibrosis bronchial epithelial cells via IKK-ß kinase pathway

¹ INSERM UMRS 514, IFR 53, CHU Maison Blanche, Reims Cedex, ² Dept of Pulmonology, Hôpital Cochin, Paris Cedex and ³ Dept of Clinical Pharmacology, GlaxoSmithKline, Marly-le-Roi, France

CORRESPONDENCE: E. Puchelle, INSERM UMRS 514, IFR 53, CHU Maison Blanche, 45 rue Cognacq Jay, 51092 Reims Cedex, France. Fax: 33 0326065861. E-mail: epuche@worldnet.fr

Keywords: airway epithelium, cystic fibrosis, cytokines, inhibitor of nuclear factor-B kinase-/ß, nuclear factor-B

Received: April 17, 2002
Accepted December 17, 2002

This work was supported in part by INSERM, a grant from GlaxoSmithKline (London, UK) and the French Association Vaincre la Mucoviscidose.

Inhaled fluticasone propionate (FP) is widely used to reduce pulmonary inflammation in chronic obstructive pulmonary disease, but the potential effects of FP on airway epithelial cells from patients with cystic fibrosis (CF) are unknown. In CF disease, a nonregulated inflammatory lung response occurs through exaggerated nuclear factor (NF)-B activation and elevated pro-inflammatory cytokines production by airway epithelial cells.

To determine whether FP reduces cytokine production in bronchial epithelial cells via NF-B, the authors investigated the nonstimulated and the Pseudomonas aeruginosa lipopolysaccharide (LPS) stimulated production of NF-B-dependent interleukin (IL)-6, IL-8 and RANTES (regulated on activation, T-cell expressed and secreted) along with the activation of NF-B in non-CF and CF human bronchial gland epithelial cells.

It was demonstrated that a relevant concentration of FP (10^–8 M) inhibited constitutive and P. aeruginosa LPS-induced IL-6 and IL-8 production of non-CF and CF bronchial epithelial cells. Interestingly, the expression of two IB kinases (IKK)-/ß, the degradation of cytosolic IB-ß inhibitor and the NF-B deoxyribonucleic acid binding activity were markedly reduced after FP treatment in both CF and non-CF bronchial epithelial cells.

It was shown by the authors that fluticasone propionate exerts an anti-inflammatory effect by blocking a signal transduction leading to a reduced level of IB-/ß kinases in bronchial epithelial cells. In particular the strong effect on the IB-ß kinase, which is known to be elevated in bronchial epithelial cells in cystic fibrosis patients, was observed.

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