Effects of the mTOR inhibitor everolimus and the PI3K/mTOR inhibitor NVP-BEZ235 in murine acute lung injury models

摘要: The mammalian target of rapamycin (mTOR) is a key signaling kinase associated with variety cellular functions including the regulation immunological and inflammatory responses. Classic mTOR inhibitors such as or everolimus are commonly used in transplant well cancer patients to prevent rejection progression, respectively. Noninfectious drug-induced pneumonitis frequent side effect mTOR-inhibitor-treated patients. Therefore, we tested effects inhibitor novel dual PI3K/mTOR NVP-BEZ235 murine lipopolysaccharide (LPS)-induced acute lung injury model. C57BL/6 mice were treated either on two consecutive days prior intratracheal administration LPS. LPS induced significant increase total cell, neutrophil erythrocyte numbers bronchoalveolar lavage fluid. Histological examination revealed serious shown by interstitial edema, vascular congestion mononuclear cell infiltration these after 24h. Everolimus did not noticeably affect overall histopathology lungs However, enhanced IL-6 TNF-α expression In contrast, levels. Interestingly, both reduced cytokines an LPS/oleic acid-induced conclusion, worsen histopathological severity, but they exerted distinct proinflammatory cytokine depending model applied.