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, Alabama
² Dept of Medicine, National Jewish Medical and Research Center, and the University of Colorado Health Sciences Center, Denver, Colorado
³ Dept of Medicine, and the Duke Asthma, Allergy and Airway Center, Duke University Medical Center, Durham, North Carolina

^* To whom correspondence should be addressed. E-mail: bfouty{at}jaguar1.usouthal.edu.

	Abstract

Corticosteroids are first line therapy for asthma. Whether they alter the progression of airway remodeling in asthma is not known.

To determine whether corticosteroids could alter fibroblast cell cycle we studied the effect of dexamethasone on cultured airway fibroblasts obtained from 9 mild to moderate, steroid naive asthmatics (FEV₁: 78±4% predicted) and 7 normal controls. Fibroblasts were cultured from endobronchial biopsies obtained via bronchoscopy. Cells were exposed to dexamethasone (10^-9 to 10^-7 M) and studied at 72 hours to determine differences in progression through the cell cycle.

In asthmatic fibroblasts dexamethasone nearly doubled the number of cells in S phase at 10^-8M (17.8±3.0%) and 10^-7M (18.4±3.1%) compared with untreated fibroblasts (10.3±1.4%; p=0.02); there was no significant effect in normal control fibroblasts. Dexamethasone induced hyperphosphorylation of the tumor 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 2 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 remodeling in some individuals remains to be determined.