Effects of Inhaled Corticosteroid Therapy on Expression and DNA-Binding Activity of Nuclear Factor κ B in Asthma

We determined whether inhaled corticosteroid therapy modulates the expression of the transcription factor, nuclear factor kappa B (NF- κ B), in patients with asthma. Fifteen stable patients with mild asthma underwent bronchoalveolar lavage (BAL) with bronchial biopsies in a double-blind, placebo-controlled and crossover study after placebo or after inhaled fluticasone propionate (500 μ g twice daily). Fluticasone reduced the number of eosinophils in BAL fluid (BALF) and in airway biopsies, together with an improvement of bronchial responsiveness to methacholine. However, NF- κ B DNA-binding in alveolar macrophages and in bronchial biopsies was not affected by fluticasone treatment. NF- κ B expression was also measured by immunohistochemical staining with an antibody to the p65 component of NF- κ B. Fluticasone caused an increase in the number of positive nuclear staining cells in the airway epithelium from 34.1 ± 5.0 to 64.1 ± 8.0 per mm2 (p = 0.002). In vitro studies of A549 epithelial cells stimulated by interleukin-1 β (IL-1 β ) showed that dexamethasone increased p65 protein expression analyzed by Western blot. Despite an anti-inflammatory effect of fluticasone, there was no decrease in NF- κ B–DNA binding and activation, indicating that this may not be a mechanism by which corticosteroids act in asthma. The significance of corticosteroid-induced increase in p65 protein expression is not known. Hart L, Lim S, Adcock I, Barnes PJ, Chung KF. Effects of inhaled corticosteroid therapy on expression and DNA-binding activity of nuclear factor κ B in asthma.