These studies are designed to investigate the potential role of peroxisome proliferator activated receptors (PPAR) in a murine model of fibrosis. In this model, intratracheal instillation of bleomycin is used to initiate pulmonary fibrosis. PPAR? knockout mice and wild type controls will be treated with bleomycin or saline and fibrogenesis. Evaluation of fibrosis will be determined up to 3 weeks after dosing. These studies will provide information on the role of the PPAR in inflammation and fibrosis. An initial experiment was conducted to evaluate the response of the PPARaKO mice to bleomycin. Mice were administered 1 mg/kg bleomycin and held for 3 weeks. At the end of the holding period, bronchoalveolar lavage fluid (BALF) was collected and lung tissues collected for histological evaluation. Cellularity of the BALF was low in a control and bleomycin-treated mice. This may be typical of this strain of mouse, or the doses of bleomycin were too low. The BALF is also being analyzed for specific mediators of inflammation. Lung tissues are being processed for histopathological evaluation.
