title: Host predisposition by endogenous Transforming Growth Factor-beta1 overexpression promotes pulmonary fibrosis following bleomycin injury.
abstract: BACKGROUND
  Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFbeta1 as a key effector cytokine in the development of lung fibrosis.
  
  
  METHODS
  In this study we have used a transgenic mouse based strategy to identify the effect of overexpression of this key effector mediator on the development of pulmonary fibrosis in response to exogenous injury. We bred two lines (line 25 and 18) of transgenic mice (Tr+) that overexpressed active TGFbeta1. Three-month old transgenic and wild type mice were subsequently wounded with intraperitoneal bleomycin. Mice were sacrificed at 6 weeks post-bleomycin and their lungs analysed histologically and biochemically.
  
  
  RESULTS
  The severity of lung fibrosis was significantly greater in the Tr+ mice compared to the wild type mice. Using an oligonucleotide microarray based strategy we identified discrete patterns of gene expression contributing to TGFbeta1 associated pulmonary fibrosis.
  
  
  CONCLUSIONS
  This data emphasises the importance of a host predisposition in the form of endogenous TGFbeta1, in the development of pulmonary fibrosis in response to an exogenous injury.
authors: National Heart and Lung Transplant Program, Mater Misericordiae University Hospital, University College Dublin, Dublin. jegan@mater.ie.
authors: Yussef
authors: Y
authors: Haider
authors: Andrea P
authors: AP
authors: Malizia
authors: Dominic T
authors: DT
authors: Keating
authors: Mary
authors: M
authors: Birch
authors: Annette
authors: A
authors: Tomlinson
authors: Gail
authors: G
authors: Martin
authors: Mark Wj
authors: MW
authors: Ferguson
authors: Peter P
authors: PP
authors: Doran
authors: Jim J
authors: JJ
authors: Egan