Rapamycin Regulates Bleomycin-Induced Lung Damage in SP-C-Deficient MiceReport as inadecuate




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Pulmonary MedicineVolume 2011 2011, Article ID 653524, 12 pages

Research Article

Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA

Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA

Received 1 September 2010; Revised 1 December 2010; Accepted 24 January 2011

Academic Editor: Akio Niimi

Copyright © 2011 Satish K. Madala et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Injury to the distal respiratory epithelium has been implicated as an underlying cause of idiopathic lung diseases. Mutations that result in SP-C deficiencies are linked to a small subset of spontaneous and familial cases of interstitial lung disease ILD and interstitial pulmonary fibrosis IPF. Gene-targeted mice that lack SP-C develop an irregular ILD-like disease with age and are a model of the human SP-C related disease. In the current study, we investigated whether rapamycin could ameliorate bleomycin-induced fibrosis in the lungs of mice. and −-− mice were exposed to bleomycin with either preventative administration of rapamycin or therapeutic administration beginning eight days after the bleomycin injury. Rapamycin-treatment increased weight loss and decreased survival of bleomycin-treated and mice. Rapamycin did not reduce the fibrotic disease in the prophylactic or rescue experiments of either genotype of mice. Further, rapamycin treatment augmented airway resistance and reduced lung compliance of bleomycin-treated mice. Rapamycin treatment was associated with an increased expression of profibrotic Th2 cytokines and reduced expression of INF-γ. These findings indicate that novel therapeutics will be required to treat individuals with SP-C deficient ILD-IPF.





Author: Satish K. Madala, Melissa D. Maxfield, Cynthia R. Davidson, Stephanie M. Schmidt, Daniel Garry, Machiko Ikegami, William D.

Source: https://www.hindawi.com/



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