Lisa Burns

Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease.

The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGFβ was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease.

House dust mite models: Will they translate clinically as a superior model of asthma?

Canada; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada; the Department of Oncology and the Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; the Division of Dermatology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; the Division of Allergy and Clinical Immunology, Department of Pediatrics, McGill University, Montreal, Quebec, Canada; the University of Dundee, Dundee, United Kingdom; Laval University, Quebec City, Quebec, Canada; the Departments of Human Genetics and Medicine, McGill University, Montreal, Quebec, Canada; Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada; Trinity College Dublin, Dublin, Ireland; and the Division of Allergy/Clinical Immunology, Department of Medicine, McGill University, Montreal, Quebec, Canada. E-mail: yuka.asai@mail.mcgill.ca. Y.A. is supported by a Canadian Institutes for Health Research Fellowship, the Allergy, Genes and Environment Network of Centres of Excellence (AllerGen NCE), and the Canadian Dermatology Foundation (CDF). C.G. is supported by the Weekend to End Cancer at the Jewish General Hospital. P.R.H. is supported by the CDF and the University of Saskatchewan’s Department of Medicine Research Fund. M.B.-S. is an Emerging Clinician-Scientist of the AllerGen NCE. S.J.B. is supported by a Wellcome Trust Intermediate Clinical Fellowship (ref 086398/Z/08/Z). A.D.I. is supported by the National Children’s Research Centre, Dublin, and the Wellcome Trust. Research in the lab of W.H.I.M. is supported by grants from the British Skin Foundation, National Eczema Society, Medical Research Council (G0700314), the Wellcome Trust (090066/B/09/Z and 092530/Z/10/Z), and donations from anonymous families affected by eczema in the Tayside Region of Scotland. TheMcGill peanut allergy case group is supported by the Foundation of the Montreal Children’s Hospital and by grants from the Canadian Allergy, Asthma, and Immunology Foundation and the AllerGen NCE. Disclosure of potential conflict of interest: Y. Asai has received research support from the Foundation of the Montreal Children’s Hospital, AllerGen NCE, Canadian Allergy, Asthma, and Immunology Foundation, and the CIHR and has received travel support from the Canadian Dermatology Foundation. S. J. Brown has received research support from the Wellcome Trust and has received travel support for the 2012 AAAAI Meeting and BSACI Meeting. J. Bussi eres and F. Rousseau have received research support from AllerGen NCE. W. H. I. McLean has received research support from the Wellcome Trust. The rest of the authors declare that they have no relevant conflicts of interest. Parts of this work have been previously presented at the Dermatogenetics Conference (Nature Genetics and Journal of Investigative Dermatology joint meeting, Miami, Florida, February 9-12, 2012) and the AllerGen NCE 2012 Annual Conference (Innovation from cell to society; Toronto, Ontario, Canada, February 5-7, 2012).