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Inhibition of notch signaling protects mouse lung against zymosan-induced injury.

Authors
Han-H; Gong-G; Bai-X; Lin-Y-C; Sun-J; Wang-; Zhao-Y; Yang-L; Wang-X; Zhang-Z; Dong-H; Hou-L; Xiong-L
Source
Shock 2013 Oct; 40(4):312-319
NIOSHTIC No.
20043828
Abstract
Notch signaling, a critical pathway in cell fate determination, is well known to be involved in immune and inflammatory reactions, whereas its role in acute lung injury (ALI) remains unclear. Here, we report that notch signal activity is upregulated in lung tissue harvested from an ALI mouse model (induced by zymosan). We showed that notch signal activity in lung tissue was increased 6 h after zymosan injection and peaked at 24 h. Inhibition of notch signaling by either pre- or post-zymosan treatment with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-(S)-phenylglycine t-butyl ester (DAPT) significantly reduced lung injury, characterized by improvement in lung histopathology, lung permeability (protein concentration in bronchoalveolar lavage fluid and lung wet-to-dry weight ratio), lung inflammation (bronchoalveolar lavage fluid cell count, lung myeloperoxidase, and tumor necrosis factor alpha), and also alleviated systemic inflammation and tissue damage, thus increasing the 7-day survival rate in zymosan-challenged mice. In conclusion, the role of notch signaling is functionally significant in the development of ALI. Inhibition of notch signaling by pretreatment or posttreatment with DAPT likely exerts its effects in part by mediating the expression of proinflammatory and anti-inflammatory cytokines and influencing tissue neutrophil recruitment. These results also imply that notch inhibitors may help attenuate local inflammatory lung damage.
Keywords
Lung-function; Lung-cells; Lung-disorders; Lung-tissue; Immune-reaction; Immune-system; Laboratory-animals; Laboratory-techniques; Laboratory-testing; Signaling-systems; Pathology; Cell-damage; Physiopathology; Organs; Enzymatic-effects; Enzyme-activity; Esters; Histopathology; Alveolar-cells; Tissue-culture; Neutrophils; Proteins
Contact
Lichao Hou, Fourth Mil Med Univ, Xijing Hosp, Dept Anesthesiol, Surg ICU, Xian 710032, Shaanxi Provinc, Peoples R China.
CODEN
SAGUAI
Publication Date
20131001
Document Type
Journal Article
Email Address
Lichao.Hou@gmail.com
Fiscal Year
2014
NTIS Accession No.
NTIS Price
Issue of Publication
4
ISSN
1073-2322
NIOSH Division
HELD
Source Name
Shock
State
WV
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