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Dexamethasone can stimulate G1-S phase transition in human airway fibroblasts in asthma

¹ Division of Pulmonary and Critical Care Medicine and the Center for Lung Biology, University of South Alabama, Mobile, AL, and ² Dept of Medicine, National Jewish Medical and Research Center, and the University of Colorado Health Sciences Center, Denver, CO, and ³ Dept of Medicine, and the Duke Asthma, Allergy and Airway Center, Duke University Medical Center, Durham, NC, USA.

CORRESPONDENCE: B. Fouty, Center for Lung Biology, MSB 3340, University of South Alabama School of Medicine, Mobile, AL, 36688, USA, Fax: 1 2514607452. E-mail: bfouty{at}jaguar1.usouthal.edu

Keywords: Asthma, cell cycle, dexamethasone, fibroblast

Received: July 5, 2005
Accepted February 21, 2006

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^-8M and 10^-7M, 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 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.