Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2018; 24(2): 216-225
Published online Jan 14, 2018. doi: 10.3748/wjg.v24.i2.216
β-arrestin 2 attenuates lipopolysaccharide-induced liver injury via inhibition of TLR4/NF-κB signaling pathway-mediated inflammation in mice
Meng-Ping Jiang, Chun Xu, Yun-Wei Guo, Qian-Jiang Luo, Lin Li, Hui-Ling Liu, Jie Jiang, Hui-Xin Chen, Xiu-Qing Wei
Meng-Ping Jiang, Chun Xu, Yun-Wei Guo, Qian-Jiang Luo, Lin Li, Hui-Ling Liu, Jie Jiang, Xiu-Qing Wei, Department of Digestive Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Chun Xu, Hui-Xin Chen, Department of Digestive Diseases, Huizhou Municipal Center Hospital, Huizhou 516002, Guangdong Province, China
Author contributions: Jiang MP, Xu C and Guo YW contributed equally to this work and performed most of the experiments; Luo QJ, Li L, Liu HL and Jiang J bred the animals and collected the animal material; Chen HX analyzed the data; and Wei XQ designed the study and wrote the paper.
Supported by the National Natural Science Foundation of China, No. 81470848; and the Breeding Foundation for Young Pioneers’ Research of Sun Yat-sen University, No. 14ykpy27.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the Third Affiliated Hospital of Sun Yat-sen University.
Institutional animal care and use committee statement: All procedures were conducted in accordance with The Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of The Third Affiliated Hospital of Sun Yat-sen University.
Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this paper.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xiu-Qing Wei, MD, PhD, Department of Digestive Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou 510630, Guangdong Province, China. weixq@mail.sysu.edu.cn
Telephone: +86-20-85252056 Fax: +86-20-85253336
Received: September 11, 2017
Peer-review started: September 12, 2017
First decision: October 18, 2017
Revised: November 3, 2017
Accepted: November 22, 2017
Article in press: November 22, 2017
Published online: January 14, 2018
Processing time: 125 Days and 1.2 Hours
Abstract
AIM

To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide (LPS)-induced liver injury in vivo and in vitro.

METHODS

Male β-arrestin 2+/+ and β-arrestin 2-/- C57BL/6J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines. Cultured cell extracts were collected to analyze the production of pro-inflammatory cytokines and expression of key molecules involved in the TLR4/NF-κB signaling pathway.

RESULTS

Compared with wild-type mice, the β-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-10. Compared with the control group, pro-inflammatory cytokines (including IL-1β, IL-6, TNF-α, and IL-10) produced by RAW264.7 cells in the β-arrestin 2 siRNA group were significantly increased at 6 h after treatment with LPS. Further, key molecules involved in the TLR4/NF-κB signaling pathway, including phospho-IκBα and phosho-p65, were upregulated.

CONCLUSION

β-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB signaling pathway-mediated inflammation.

Keywords: Lipopolysaccharide; Liver injury; β-arrestin 2; TLR4/NF-κB signaling pathway; Pro-inflammatory cytokines

Core tip: The role and mechanism of β-arrestin 2 in lipopolysaccharide (LPS)-induced liver injury remain unclear. In this study, β-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of pro-inflammatory cytokines than wild-type mice. Further, RAW264.7 cells treated with β-arrestin 2 siRNA expressed significantly higher pro-inflammatory cytokines and molecules involved in the TLR4/NF-κB signaling pathway (including phospho-IκBα and phosho-p65) than the control group at 6 h after treatment with LPS. Therefore, β-arrestin 2 could protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB-mediated inflammation and may serve as a therapeutic target.