Journal article
Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis
RJJ O'Donoghue, DA Knight, CD Richards, CM Prêle, HL Lau, AG Jarnicki, J Jones, S Bozinovski, R Vlahos, S Thiem, BS McKenzie, B Wang, P Stumbles, GJ Laurent, RJ McAnulty, S Rose-John, HJ Zhu, GP Anderson, MR Ernst, SE Mutsaers
EMBO Molecular Medicine | Published : 2012
Abstract
Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is unresponsive to current therapies and characterized by excessive collagen deposition and subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)-6, are elevated in IPF, the molecular mechanisms that underlie this disease are incompletely understood, although the development of fibrosis is believed to depend on canonical transforming growth factor (TGF)-β signalling. We examined bleomycin-induced inflammation and fibrosis in mice carrying a mutation in the shared IL-6 family receptor gp130. Using genetic complementation, we directly correlate the extent of IL-6-mediated, excessive Stat3 activity with inflamma..
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Awarded by Medical Research Council
Funding Acknowledgements
The authors would like to acknowledge Dr Toby Phesse and Dr Tracy Putoczki for critical reading of the manuscript and the technical assistance of Ms Dianne Grail, Ms Danielle Copeman, Ms Lovisa Dousha, Dr Vance Matthews, Dr Deborah Strickland and the Centre for Microscopy, Characterization and Analysis of the University of Western Australia. This work was supported by funds from the Operational Infrastructure Support Program provided by the Victorian Government, the National Health and Medical Research Council (NHMRC) of Australia, grants 3030137 and 458703, and is solely the responsibility of the institution or individual authors and does not reflect the views of NHMRC. RJJO'D was in part supported through an Australian Postgraduate Award from the University of Western Australia, Lung Institute of Western Australia PhD top-up scholarship and an unrestricted research grant from Roche awarded to GPA. DAK is a Canada Research Chair and Michael Smith Foundation Senior Scholar supported by a Canadian Institute of Health Research grant and gifts from the Rasphal Dhillon fund for IPF research. ME is a Senior Research Fellow of the NHMRC.