Authors: Shufei Zang Lei Wang Xiaojie Ma Geli Zhu Zhenjie Zhuang Yunhao Xun Falin Zhao Wenjun Yang Juan Liu Yan Luo Yinlan Liu Dewei Ye Junping Shi
Publish Date: 2015/05/23
Volume: 73, Issue: 2, Pages: 479-487
Abstract
Neutrophils infiltration in liver is one of the typical histological characteristics of nonalcoholic steatohepatitis NASH in both animal models and human subjects This study was aimed to investigate the role of neutrophils in the process of NASH and its underling mechanisms C57BL/6J mice were fed with either standard chow SC or methionine/cholinedeficient MCD diet for 1 2 4 8 weeks respectively C57BL/6J APOE−/− mice were fed with SC or highfat highcholesterol HFHC diet AntiLy6G antibody was employed to deplete neutrophils and sivelestat was used to inhibit neutrophil elastase NE MCDdietreceiving mice with neutrophil depletion had much lower serum ALT activity liver inflammation and mRNA levels of proinflammatory genes in the early stage of NASH 1 and 2 weeks when compared to nonneutrophildepleted mice NE inhibitor sivelestat could recapitulate the effects of neutrophil depletion in APOE−/− mice fed with HFHC diet As the disease progressed 4 and 8 weeks neutrophil depletion did not lower serum ALT levels and liver lesions due to activation of Kupffer cells Finally we found neutrophils also affected antiinflammation cytokine interleukin1 receptor antagonist mRNA expression Neutrophils play a crucial role in the early stage of NASH via NE
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