title: Dexamethasone and salbutamol stimulate human lung fibroblast proliferation.
abstract: BACKGROUND
  Asthma is characterized by bronchial hyperreactivity and airway remodeling. Subepithelial fibrosis, a feature of remodeling, is accompanied by activation of fibroblasts to myofibroblasts, with excessive proliferation and increased collagen, extracellular matrix protein, and profibrogenic cytokine production. Mast cells are important in the development of asthma and its fibrotic changes.
  
  
  OBJECTIVE
  In this study, we aimed to investigate the direct effect of the drugs most frequently used in asthma, that is, glucocorticosteroids (dexamethasone) and shortacting β(2)-agonists (salbutamol), on human lung fibroblast proliferation when unstimulated or activated by mast cells or eotaxin.
  
  
  METHODS
  Subconfluent human fetal lung or bronchial fibroblasts were incubated with different concentrations of the drugs (24 h) 6 activators, and [(3)H]-Thymidine was added (24 h) to measure their proliferation. IL-6 production in the supernatants of confluent monolayers cultured in the presence of the drugs or forskolin (24 h) was analyzed by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Both drugs alone and in the presence of the activators enhanced fibroblast proliferation in a seemingly synergistic way for both fetal and bronchial fibroblasts. Dexamethasone was found to decrease IL-6 production, while salbutamol increased it.
  
  
  CONCLUSIONS
  These observations if corroborated by in vivo data may possibly account for the deleterious effect of long-term therapy with β(2)-bronchodilators and inhaled glucocorticosteroids on the natural history of asthma.
authors.affiliation: Department of Pharmacology, Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Pickholtz
authors.forename: Dan
authors.initials: D
authors.lastname: Admon
authors.forename: Uzi
authors.initials: U
authors.lastname: Izhar
authors.forename: Neville
authors.initials: N
authors.lastname: Berkman
authors.forename: Francesca
authors.initials: F
authors.lastname: Levi-Schaffer