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On-line Access: 2022-04-22

Received: 2020-12-17

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Qingqing WANG


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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.7 P.590-598


Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response

Author(s):  Yuhua LIU, Xiaopeng WAN, Yuan YUAN, Jingjing HUANG, Yijia JIANG, Kaiyue ZHAO, Yan WANG, Yang LIU, Qingqing WANG, Hongchuan JIN

Affiliation(s):  Laboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou 310016, China; more

Corresponding email(s):   wqq@zju.edu.cn, jinhc@zju.edu.cn

Key Words:  Toll-like receptor 4 (TLR4), Endotoxin tolerance, MicroRNA-155 (miR-155), Suppressor of cytokine signaling 1 (SOCS1), Transforming growth factor-β, -activated kinase 1-binding protein 2 (TAB2)

Yuhua LIU, Xiaopeng WAN, Yuan YUAN, Jingjing HUANG, Yijia JIANG, Kaiyue ZHAO, Yan WANG, Yang LIU, Qingqing WANG, Hongchuan JIN. Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response[J]. Journal of Zhejiang University Science B, 2021, 22(7): 590-598.

@article{title="Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response",
author="Yuhua LIU, Xiaopeng WAN, Yuan YUAN, Jingjing HUANG, Yijia JIANG, Kaiyue ZHAO, Yan WANG, Yang LIU, Qingqing WANG, Hongchuan JIN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response
%A Yuhua LIU
%A Xiaopeng WAN
%A Yuan YUAN
%A Jingjing HUANG
%A Yijia JIANG
%A Kaiyue ZHAO
%A Yang LIU
%A Qingqing WANG
%A Hongchuan JIN
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 7
%P 590-598
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000826

T1 - Opposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response
A1 - Yuhua LIU
A1 - Xiaopeng WAN
A1 - Yuan YUAN
A1 - Jingjing HUANG
A1 - Yijia JIANG
A1 - Kaiyue ZHAO
A1 - Yan WANG
A1 - Yang LIU
A1 - Qingqing WANG
A1 - Hongchuan JIN
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 7
SP - 590
EP - 598
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000826

Although microRNA-155 (miR-155) is considered a pro-inflammatory mediator, cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells. In this study, we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide (LPS) stimulation; 223 genes were down-regulated and 85 genes were up-regulated, including suppressor of cytokine signaling 1 (SOCS1) and transforming growth factor-β;-activated kinase 1-binding protein 2 (TAB2), two well-known genes involved in miR-155-mediated regulation of the toll-like receptor 4 (TLR4) signaling pathway. We also found that miR-155 acted as an anti-inflammatory mediator in the initial stage of LPS-induced inflammatory response mainly through repressing TAB2 protein translation, and as a pro-inflammatory mediator by down-regulating SOCS1 in the later stage. Meanwhile, overexpression of TAB2 3' untranslated region (UTR) in macrophages promoted the development of endotoxin tolerance by competing for binding with miR-155, which resulted in an elevated expression level of SOCS1 protein. These findings provide new insights for understanding the regulatory mechanisms in fine-tuning of LPS-induced innate immune response.


方法:采用二代转录组测序检测脂多糖刺激下的巨噬细胞内miR-155靶基因池的改变;并分析核糖体测序数据验证miR-155的靶基因的翻译效率;采用实时定量聚合酶链反应(RT-qPCR)和免疫印迹(western blotting)明确靶基因的表达;采用荧光素酶报告基因系统和生物素介导的microRNA pulldown技术明确miR-155和靶基因在不同时相的结合;通过脂多糖体外刺激巨噬细胞,建立内毒素耐受模型,并采用酶联免疫吸附测定(ELISA)检测炎症因子的分泌水平。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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