Rapamycin regulates bleomycin-induced lung damage in SP-C-deficient mice

Satish K. Madala, Melissa D. Maxfield, Cynthia R. Davidson, Stephanie M. Schmidt, Daniel Garry, MacHiko Ikegami, William D. Hardie, Stephan W. Glasser

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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 (Sftpc-/-) 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 Sftpc-/- mice. Sftpc +/+ 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 Sftpc+/+ and Sftpc -/- 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 Sftpc-/- mice. Rapamycin treatment was associated with an increased expression of profibrotic Th2 cytokines and reduced expression of INF-. These findings indicate that novel therapeutics will be required to treat individuals with SP-C deficient ILD/IPF.

Original languageEnglish (US)
Article number653524
JournalPulmonary Medicine
DOIs
StatePublished - 2011

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