Inhibition of Notch Signaling Protects Mouse Lung Against Zymosan-Induced Injury

• DOI: 10.1097/shk.0b013e3182a102e5
• Publication Date: 2013-06-26T11:20:22Z
• Authors: Han Han; Gu Gong; Xiaoguang Bai; Yen-Chang Lin; Jing Sun; Wenyong Wang; Yiling Zhao; Lifang Yang; Xiaoxia Wang; Zexin Zhang; Hailong Dong; Lichao Hou; Lize Xiong
• Keywords: Zymosan; Proinflammatory cytokine

Notch signaling, a critical pathway in cell fate determination, is well known to be involved immune and inflammatory reactions, whereas its role acute lung injury (ALI) remains unclear. Here, we report that notch signal activity upregulated tissue harvested from an ALI mouse model (induced by zymosan). We showed was increased 6 h after zymosan injection peaked at 24 h. Inhibition of signaling either pre- or post-zymosan treatment with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-(S)-phenylglycine t-butyl ester (DAPT) significantly reduced injury, characterized improvement histopathology, permeability (protein concentration bronchoalveolar lavage fluid wet-to-dry weight ratio), inflammation (bronchoalveolar count, myeloperoxidase, tumor necrosis factor α), also alleviated systemic damage, thus increasing the 7-day survival rate zymosan-challenged mice. In conclusion, functionally significant development ALI. pretreatment posttreatment DAPT likely exerts effects part mediating expression proinflammatory anti-inflammatory cytokines influencing neutrophil recruitment. These results imply inhibitors may help attenuate local damage.