Dexamethasone can stimulate G1-S phase transition in human airway fibroblasts in asthma.
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.
Fouty
B
B
Center for Lung Biology, MSB 3340, University of South Alabama School of Medicine, Mobile, AL, 36688, USA. bfouty@jaguar1.usouthal.edu
Moss
T
T
Solodushko
V
V
Kraft
M
M
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000473:pathology*; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000473:pathology*; D001999:Bronchoscopy; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D016193:G1 Phase / Q000187:drug effects*; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000187:drug effects; D016196:S Phase / Q000187:drug effects*; D013268:Stimulation, Chemical
D000893:Anti-Inflammatory Agents; D016160:Retinoblastoma Protein; D003907:Dexamethasone