Altered gp130-mediated signalling in the regulation of pulmonary fibrosis [ 2007 - 2008 ]

Research Grant

Researchers: A/Pr Steven Mutsaers (Principal investigator) ,  Prof Darryl Knight ,  Prof Matthias Ernst

Brief description Pulmonary fibrosis is a chronic diffuse interstitial lung disease often of unknown cause, characterised pathologically by inflammation and fibrosis of the lung tissue. The prognosis is poor with a 50% mortality at five years after diagnosis and considerable morbidity during those years. Previous investigations have documented the role for inflammation in the development of pulmonary fibrosis and current therapeutic strategies are aimed at suppressing the inflammation using anti- inflammatory drugs, almost exclusively steroids. The effectiveness of steroids is variable although generally poor and can be associated with significant side effects suggesting that other approaches need to be considered. Data generated over the past decade also have established the concept that the molecular processes underlying the development of fibrosis may represent a new opportunity for therapeutic intervention. This project will build on previous studies examining the effects of a family of molecules called cytokines that signal through gp130 as critical determinants of disease susceptibility and progression. gp 130 is a shared component in the receptor complexes for IL-6 family cytokines and can signal down two major pathways. We have shown that the development of lung fibrosis depends on which specific signalling pathway is used. This study will determine how fibrosis is controlled by these pathways. Our data raises the possibility of developing pharmacological manipulators of gp130 signalling pathways that would suppress fibrosis but leave normal cellular defense mechanisms necessary for host defense in the lung intact.

Funding Amount $AUD 373,956.80

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant