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

Published

Journal Article

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.

Full Text

Cited Authors

  • Fouty, B; Moss, T; Solodushko, V; Kraft, M

Published Date

  • June 2006

Published In

Volume / Issue

  • 27 / 6

Start / End Page

  • 1160 - 1167

PubMed ID

  • 16510457

Pubmed Central ID

  • 16510457

Electronic International Standard Serial Number (EISSN)

  • 1399-3003

International Standard Serial Number (ISSN)

  • 0903-1936

Digital Object Identifier (DOI)

  • 10.1183/09031936.06.00078605

Language

  • eng