Corticosteroids are the first line of
therapy for
asthma. Whether they alter the progression of
airway remodelling in
asthma is, as yet, unknown. To determine whether
corticosteroids could alter the fibroblast cell cycle the current authors studied the effect of
dexamethasone on cultured airway fibroblasts obtained from nine mild-to-moderate,
steroid-naïve asthmatics (forced expiratory volume in one second 78+/-4% predicted), and seven normal controls. Fibroblasts were cultured from endobronchial biopsies obtained via bronchoscopy. Cells were exposed to
dexamethasone (10(-9)-10(-7) M) and studied at 72 h to determine differences in progression through the cell cycle. In asthmatic fibroblasts,
dexamethasone, at concentrations of 10(-8)M and 10(-7)M, nearly doubled the number of cells in the S phase (17.8+/-3.0% and 18.4+/-3.1%, respectively) compared with untreated fibroblasts (10.3+/-1.4%). There was no significant effect in normal control fibroblasts.
Dexamethasone induced hyperphosphorylation of the tumour suppressor,
retinoblastoma (RB) in asthmatic fibroblasts; fibroblasts from normal controls had significantly less hyperphosphorylation of RB. No difference in
protein expression of the
CCAAT/enhancer binding protein alpha between the two groups was detected. This study suggests that
dexamethasone can stimulate G1-S phase cell cycle transition in human airway fibroblasts obtained from asthmatics. Whether this leads to enhanced
airway remodelling in some individuals remains to be determined.