Research

Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury

Yussef Haider¹ , Andrea P Malizia² , Dominic T Keating² , Mary Birch¹ , Annette Tomlinson¹ , Gail Martin¹ , Mark WJ Ferguson¹ , Peter P Doran³ and Jim J Egan^2,4

¹School of Biological Sciences, University of Manchester, Manchester, UK

²National Heart and Lung Transplant Program, Mater Misericordiae University Hospital, University College Dublin, Dublin

³Genome Resource Unit, Dublin Molecular Medicine Centre, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland

⁴Advanced Lung Disease Programme, Mater Misericordiae University Hospital, University College Dublin, 44 Eccles Street, Dublin 7, Ireland

author email corresponding author email

Journal of Inflammation 2007, 4:18doi:10.1186/1476-9255-4-18

Published:	20 September 2007

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 TGFβ1 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 TGFβ1. 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 TGFβ1 associated pulmonary fibrosis.

Conclusion

This data emphasises the importance of a host predisposition in the form of endogenous TGFβ1, in the development of pulmonary fibrosis in response to an exogenous injury.