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Bradykinin contributes to immune liver injury via B2R receptor-mediated pathways in trichloroethylene sensitized mice: A role in Kupffer cell activation

Zhang, Jiaxiang, Li, Na, Yang, Ling, Xie, Haibo, Yang, Yi, Wang, Hui, Wu, Changhao, Shen, Tong and Zhu, Qixing (2019) Bradykinin contributes to immune liver injury via B2R receptor-mediated pathways in trichloroethylene sensitized mice: A role in Kupffer cell activation TOXICOLOGY, 415. pp. 37-48.

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Abstract

We have previously shown trichloroethylene (TCE) induced occupational medicamentosa-like dermatitis due to TCE (OMLDT) with immune liver injury, and kallikrein-kinin system (KKS) activation as a probably mechanism underlying the immune damage. Bradykinin (BK) is an important active component of KKS system function, but the specific role of BK in the immune liver injury has never been examined. The present study aimed to explore the important role of BK and mechanisms of action in immune liver injury induced by TCE. TCE sensitization significantly increased the expression of BK receptor (B2R) in the liver. Compared to blank and vehicle control group, TCE sensitization positive mice developed exacerbated liver injury evidenced by elevated AST, ALT levels and hepatocyte damage. TCE sensitization also stimulated MAPK and STAT3 activation in liver tissue. B2R antagonist HOE140 ameliorated these changes. Kupffer cells (KCs) of the liver were also activated following TCE sensitization; both CD68+ KCs and CD16/CD32+ M1 type KCs were increased in TCE positive group. Further experiments isolated the KCs from the liver in each group and showed that TCE sensitization resulted activation of MAPK signal pathway which in turn caused release of the pro-inflammatory cytokines, IL-1β, IL-6, TNF-α, in KCs; the antagonist HOE140 again decreased these changes in KCs. These results uncover a novel role of BK and B2R cross-talk in KCs activation in TCE sensitized mice, mediated by pro-inflammatory cytokine release via MAPK and STAT3 activation, contributing to the immune liver injury.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Zhang, Jiaxiang
Li, Na
Yang, Ling
Xie, Haibo
Yang, Yi
Wang, Hui
Wu, ChanghaoC.Wu@surrey.ac.uk
Shen, Tong
Zhu, Qixing
Date : 24 January 2019
DOI : 10.1016/j.tox.2019.01.015
Copyright Disclaimer : © 2019 Elsevier B.V. All rights reserved.
Uncontrolled Keywords : Trichloroethylene; Bradykinin; Liver injury; Kupffer cell
Depositing User : Diane Maxfield
Date Deposited : 09 Apr 2019 11:14
Last Modified : 25 Jan 2020 02:08
URI: http://epubs.surrey.ac.uk/id/eprint/851032

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