PT  - JOURNAL ARTICLE
AU  - Sandie Escotte
AU  - Claire Danel
AU  - Dominique Gaillard
AU  - Sylvie Benoit
AU  - Jacky Jacquot
AU  - Daniel Dusser
AU  - Jean-Michel Triglia
AU  - Caroline Majer-Teboul
AU  - Edith Puchelle
TI  - Fluticasone Propionate Inhibits Lipopolysaccharide-Induced Proinflammatory Response in Human Cystic Fibrosis Airway Grafts
AID  - 10.1124/jpet.102.033407
DP  - 2002 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1151--1157
VI  - 302
IP  - 3
4099  - http://jpet.aspetjournals.org/content/302/3/1151.short
4100  - http://jpet.aspetjournals.org/content/302/3/1151.full
SO  - J Pharmacol Exp Ther2002 Sep 01; 302
AB  - Airway inflammation, one of the major factors leading to lung damage in cystic fibrosis (CF) patients, is associated with an abnormal increase in proinflammatory cytokines. In this work, we demonstrate the increased release of the proinflammatory cytokines after lipopolysaccharide (LPS) stimulation: human interleukin (hIL)-8 in CF and non-CF airway xenografts, and hIL-6 and human growth-related oncogene-α (hGRO-α), which could be only analyzed in non-CF xenografts. Under basal conditions, we observed that hIL-8 was higher in CF xenografts compared with non-CF. We also report the anti-inflammatory effect of a glucocorticoid, fluticasone propionate (FP), on CF airway epithelium using a humanized model of airway inflammation developed in nude mice. In CF and non-CF tracheal xenografts, airway inflammation was induced by inoculatingPseudomonas aeruginosa LPS (4 h; 1 μg/ml) in the lumen of the xenografts. FP pretreatment (2 h; 10−8 M) followed by P. aeruginosa LPS stimulation induced a significant reduction of LPS-induced hIL-8 release in airway liquid collected from CF and non-CF tracheal xenografts (85 and 80%, respectively). In non-CF tracheal xenografts, FP treatment before LPS stimulation induced a significant decrease in hIL-6 and hGRO-α. From these data, we suggest that FP exerts anti-inflammatory properties that may be appropriate to CF therapy, at an early stage of the disease. In addition, these results demonstrate that the humanized airway model of inflammation provides a relevant tool for analyzing the effects of anti-inflammatory drugs in different diseases in which airway inflammation is implicated. The American Society for Pharmacology and Experimental Therapeutics