Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2015; 21(11): 3239-3244
Published online Mar 21, 2015. doi: 10.3748/wjg.v21.i11.3239
Effects of urotensin-II on cytokines in early acute liver failure in mice
Liang-Ming Liu, Liang Zhao, Dong-Yu Liang, Fang-Ping Yu, Chang-Gen Ye, Wen-Juan Tu, Tong Zhu
Liang-Ming Liu, Liang Zhao, Dong-Yu Liang, Fang-Ping Yu, Chang-Gen Ye, Wen-Juan Tu, Tong Zhu, Department of Hepatology, Songjiang Hospital Affiliated to the First People’s Hospital, Shanghai Jiaotong University, Shanghai 201600, China
Author contributions: Liu LM designed research; Zhao L, Liang DY, Yu FP, Ye CG, Tu WJ and Zhu T performed research; Liu LM contributed new reagents/analytic tools; Liu LM and Zhao L analyzed data; and Liu LM and Zhao L wrote the paper.
Supported by National Natural Science Foundation of China, No. 81070357 and No. 30660066.
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: Liang-Ming Liu, MD, PhD, Department of Hepatology, Songjiang Hospital Affiliated to the First People’s Hospital, Shanghai Jiaotong University, No. 746 Mid-Zhongshan Road, Songjiang District, Shanghai 201600, China. liuliangming@hotmail.com
Telephone: +86-21-67720053 Fax: +86-21-67720053
Received: July 7, 2014
Peer-review started: July 8, 2014
First decision: September 15, 2014
Revised: October 23, 2014
Accepted: December 16, 2014
Article in press: December 16, 2014
Published online: March 21, 2015
Abstract

AIM: To investigate urotensin-II (UII) and its effects on tumor necrosis factor (TNF)-α and interleukin (IL)-1β in early acute liver failure (ALF).

METHODS: We investigated the time-dependent alteration in UII levels and its effects on TNF-α and IL-1β in liver and blood in the early stage of lipopolysaccharide/D-galactosamine-induced ALF.

RESULTS: After lipopolysaccharide/D-galactosamine challenge, UII rose very rapidly and reached a maximal level 0.5 h, and the level remained significantly elevated after 2 h (P < 0.05). Six hours after challenge, UII began to degrade, but remained higher than at 0 h (P < 0.05). Pretreatment with urantide, an inhibitor of the UII receptor, suppressed the degree of UII increase in liver and blood at 6 h after challenge (P < 0.05 vs paired controls). In addition, liver and blood TNF-α increased from 1 to 6 h, and reached a peak at 1 and 2 h, respectively; however, IL-1β did not rise until 6 h after challenge. Urantide pretreatment inhibited the degree of TNF-α and IL-1β increase following downregulation of UII post-challenge (all P < 0.05).

CONCLUSION: UII plays a role in the pathogenesis and priming of ALF by triggering an inflammatory cascade and driving the early release of cytokines in mice.

Keywords: Acute hepatic failure, Interleukin-1β, Mouse, Tumor necrosis factor α, Urantide, Urotensin-II

Core tip: In this study, we found that urotensin-II (UII) increased before tumor necrosis factor (TNF)-α and interleukin (IL)-1β following lipopolysaccharide/D-galactosamine challenge. Furthermore, pretreatment with urantide, an inhibitor of the UII receptor, blocked TNF-α and IL-1β increases following downregulation of UII in liver and blood at different time points after challenge. Therefore, UII may play a pivotal role in the pathogenesis and priming of acute liver failure by triggering the inflammatory cascade, and initiating and driving the early release of TNF-α and IL-1β in lipopolysaccharide/D-galactosamine-challenged mice.