P087 Inhibition of pleural inflammation hampers with bleomycin-induced lung profibrotic toxicity.

Abstract : The clinical use of bleomycin is restrained because of its lung toxicity with pulmonary fibrosis being the most devastating form. Toxic and idiopathic pulmonary fibrosis (PF) start classically in the subpleural area. It is known that 1) pleural mesothelial cells (PMCs) acquire a TGF-beta1-induced myofibroblast phenotype and 2) inflammation plays a significant role in fibrogenesis. The role of mesothelial cells in PF and in bleomycin lung toxicity has still to be investigated. C57Bl/6 mice were intravenously injected with bleomycin or NaCl. Repeated intravenous bleomycin induces a peculiar lung fibrotic response with 1) an histological peripheral distribution, 2) a collagen accumulation in pleural and subpleural area, 3) an overexpression of MMP-2, -9, HSP27, all involved in PMCs transformation and 4) a migration of PMCs into the lung....