The effect of fluticasone propionate on respiratory syncytial virus-induced chemokine release by a human bronchial epithelial cell line.
Respiratory syncytial virus (RSV) is an important cause of bronchiolitis in infants, is an important trigger of asthma exacerbation, and stimulates chemokine production by human respiratory epithelial cells in vitro. We tested the effect of the corticosteroid fluticasone propionate (FP) on RSV-stimulated production of the chemokines interleukin 8 (IL-8) and RANTES (regulated upon activation, normal T cell expressed and secreted) by a human bronchial epithelial cell line, BEAS-2B. Confluent BEAS-2B cultures were inoculated with RSV at approximately 1 plaque-forming unit/cell, and media were collected at 24 h intervals. Concentrations of IL-8 and RANTES were measured in supernatants using ELISA. The effect of FP at varying concentrations on RSV-induced chemokine release was determined. RSV stimulated increased release of both IL-8 and RANTES, particularly at 24-48 h after virus inoculation. Significant but incomplete inhibition of RSV-stimulated increases for both chemokines was found when cultures were treated with FP at > or = 10(-8) M (for IL-8) or > or = 10(-7) M (for RANTES). There was no significant effect of FP on release of RSV itself from infected BEAS-2B cells. We conclude that a possible mechanism for the efficacy of inhaled corticosteroids in reducing the frequency or severity of asthma exacerbations is inhibition of virus-induced chemokine production by airway cells.
Noah
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Center for Environmental Medicine and Lung Biology, The University of North Carolina at Chapel Hill 27599-7220, USA. noah.terry@epamail.epa.gov
Wortman
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IA
Becker
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D000730:Androstadienes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001980:Bronchi / Q000378:metabolism* / Q000821:virology*; D002460:Cell Line; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D000068298:Fluticasone; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism*; D018113:Respiratory Syncytial Virus, Human
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D018946:Chemokine CCL5; D016209:Interleukin-8; D000068298:Fluticasone