|Table of Contents|

IL-17A knockout alleviates lipopolysaccharide-induced steatotic liver injury in mice

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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

Issue:
2017年第16期
Page:
1599-1605
Research Field:
基础医学
Publishing date:

Info

Title:

IL-17A knockout alleviates lipopolysaccharide-induced steatotic liver injury in mice

Author(s):

XIANG Wei WANG Xiaodong LI Zhengyan XIE Bin GAN Lixia

Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, 400038; 3Department of Hepatobiliary Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China

Keywords:

IL-17A fatty liver LPS liver injury hydrogen peroxide metabolism

PACS:
R392-33;R392.3;R575.5
DOI:
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Abstract:

Objective      To investigate the effect of interleukin 17A (IL-17A)deficiency on lipopolysaccharide(LPS)-induced liver injury in mice with long-term high fat diet feeding and explore the underlying mechanism. Methods     C57BL/6 mice with IL-17A gene knockout (KO) and the wild-type (WT) littermates fed with high fat diet for 3 months were given an intraperitoneal injection of 4 mg/kg lipopolysaccharide (LPS). Plasma levels of alanine transaminase(ALT) and aspartate transaminase (AST) were detected to assess liver injury. Plasma TNF-α, IL-1β and IL-6 levels were determined to assess the severity of inflammation. Inflammatory cell infiltration in the liver and the impairment of hepatic cells were observed. The liver tissues from the WT and KO mice were subjected to transcriptomic analysis to study the effect of IL-17A deficiency on high-fat-diet- and LPS-induced liver injuries. Results     High fat diet feeding and LPS challenge significantly decreased the plasma ALT and AST levels in IL-17A KO mice (P<0.05). In the KO mice,the plasma levels of inflammatory cytokines and the number of infiltrating inflammatory cells in the liver were reduced significantly(P<0.05). Transcriptomic analysis showed that 938 genes were down-regulated in the KO mice after LPS stimulation, among which the genes involved in oxidation reduction process(P<0.01), hydrogen peroxide metabolic process (P<0.01), and glutathione metabolic process (P<0.01) showed the most significant decreases. Real-time PCR demonstrated that a panel of metabolic enzymes participated in hydrogen peroxide detoxification, such as CAT, GPX1, IDH1, IDH2 and ME1, which were highly expressed in the KO mice (P<0.05). The levels of reactive oxygen species (ROS) were significantly decreased in the liver of KO mice (P<0.05). TUNEL assay indicated that the number of apoptotic cells was significantly reduced in the liver of KO mice(P<0.05). Conclusion      IL-17A deficiency may alleviate LPS-induced acute inflammatory injury in fatty liver mice by reducing hepatic ROS accumulation.

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Last Update: 2017-08-18