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过表达pellino-1在Kupffer细胞内毒素耐受时对TRAF3泛素化及MAPK信号通路的调控

张译尹 李培志 廖锐 龚建平

中山大学学报(医学科学版)2017,Vol.38Issue(5):658-664,7.
中山大学学报(医学科学版)2017,Vol.38Issue(5):658-664,7.

过表达pellino-1在Kupffer细胞内毒素耐受时对TRAF3泛素化及MAPK信号通路的调控

Role of Pellino-1 Overexpression on Ubiquitin of Tumor Necrosis Factor Receptor-associated Factors 3 and MAPK Signaling Pathway in Endotoxin-tolerant Kupffer Cells

张译尹 1李培志 1廖锐 2龚建平1

作者信息

  • 1. 重庆医科大学附属第二医院肝胆外科,重庆 400016
  • 2. 重庆医科大学附属第一医院肝胆外科,重庆 400016
  • 折叠

摘要

Abstract

[Objective]To investigate the effect of pellino-1 gene overexpression by lentivirus vector on the ubiquitin of tumor necrosis factor receptor-associated factors 3 (TRAF3) and the activation of mitogen-activated protein kinases (MAPK) signaling pathway in endotoxin-tolerant kupffer cells (KCs).[Methods]Isolated KCs of C57BL/6 mouse were randomly divided into two groups:control group,which transfected with control lentivirus vector for 48 h,then pretreated with 10 ng/mL lipopolysaccharide (LPS)for 24 h,and next treated with 300 ng/mL LPS;overexpression group,which transfected with pellino-1 gene overexpression lentivirus vector for 48 h,then pretreated with 10 ng/mL lipopolysaccharide(LPS)for 24 h,and next treated with 300 ng/mL LPS. The protein expressions of pellino-1,K48-Ub,TRAF3,p38,p-p38,c-Jun N-terminal kinase(JNK)and p-JNK were analyzed by Western blot. The level of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in superna-tants were measured by enzyme linked immunosorbent assay(ELISA).[Results]Compared with control group,the protein expres-sions of pellino-1,K48-Ub,p-JNK and p-p38 and the levels of IL-1β(P < 0.05),TNF-α(P < 0.05)in supernatants was in-creased in overexpression group,while the protein levels of TRAF3 and the levels of IL-10(P < 0.05)in supernatants were de-creased.[Conclusion]Overexpression of pellino-1 can promote TRAF3 K48 ubiquitination degradation,decrease the protein expres-sion of TRAF3,activate the downstream MAPK signaling pathway,and thus impair the formulation of endotoxin tolerance.

关键词

kupffer细胞/内毒素耐受/pellino-1/肿瘤坏死因子受体相关因子3

Key words

Kupffer cells/endotoxin tolerance/pellino-1/TRAF3

分类

医药卫生

引用本文复制引用

张译尹,李培志,廖锐,龚建平..过表达pellino-1在Kupffer细胞内毒素耐受时对TRAF3泛素化及MAPK信号通路的调控[J].中山大学学报(医学科学版),2017,38(5):658-664,7.

基金项目

国家自然科学青年基金(81401622 ()

81301656) ()

重庆市科委基础科学与前沿技术研究专项(重点,cstc2015 jcyjBX0070) (重点,cstc2015 jcyjBX0070)

中山大学学报(医学科学版)

OA北大核心CSCDCSTPCD

1672-3554

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