Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2017; 23(31): 5700-5712
Published online Aug 21, 2017. doi: 10.3748/wjg.v23.i31.5700
Schistosoma japonicum attenuates dextran sodium sulfate-induced colitis in mice via reduction of endoplasmic reticulum stress
Ya Liu, Qing Ye, Yu-Lan Liu, Jian Kang, Yan Chen, Wei-Guo Dong
Ya Liu, Jian Kang, Yan Chen, Wei-Guo Dong, Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Qing Ye, Department of Hospital Infection, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Yu-Lan Liu, Departments of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Author contributions: Liu Y and Ye Q contributed equally to this work; Liu Y, Ye Q, Liu YL, Chen Y and Kang J performed the experiments and analysed the data; Liu Y wrote the manuscript; Ye Q revised the manuscript; all authors have read and approved this manuscript.
Institutional review board statement: This study was reviewed and approved by Wuhan University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Wuhan University.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
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: Wei-Guo Dong, MD, PhD, Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, Hubei Province, China. dwg@whu.edu.cn
Telephone: +86-27-88041911 Fax: +86-27-88042292
Received: February 16, 2017
Peer-review started: February 22, 2017
First decision: March 3, 2017
Revised: March 30, 2017
Accepted: April 21, 2017
Article in press: April 21, 2017
Published online: August 21, 2017
Processing time: 184 Days and 7.4 Hours
Abstract
AIM

To elucidate the impact of Schistosoma (S.) japonicum infection on inflammatory bowel disease by studying the effects of exposure to S. japonicum cercariae on dextran sodium sulfate (DSS)-induced colitis.

METHODS

Infection was percutaneously established with 20 ± 2 cercariae of S. japonicum, and colitis was induced by administration of 3% DSS at 4 wk post infection. Weight change, colon length, histological score (HS) and disease activity index (DAI) were evaluated. Inflammatory cytokines, such as IL-2, IL-10 and IFN-γ, were tested by a cytometric bead array and real-time quantitative polymerase chain reaction (RT-PCR). Protein and mRNA levels of IRE1α, IRE1β, GRP78, CHOP, P65, P-P65, P-IκBα and IκBα in colon tissues were examined by Western blot and RT-PCR, respectively. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positive cells, cleaved-caspase 3 expression and Bcl2/Bax were investigated to assess the apoptosis in colon tissues.

RESULTS

Mice infected with S. japonicum cercariae were less susceptible to DSS. Mice infected with S. japonicum cercariae and treated with DSS showed decreased weight loss, longer colon, and lower HS and DAI compared with mice treated with DSS alone. A substantial decrease in Th1/Th2/Th17 response was observed after infection with S. japonicum. Endoplasmic reticulum (ER) stress and the nuclear factor-kappa B (NF-κB) pathway were reduced in mice infected with S. japonicum cercariae and treated with DSS, along with ameliorated celluar apoptosis, in contrast to mice treated with DSS alone.

CONCLUSION

Exposure to S. japonicum attenuated inflammatory response in a DSS-induced colitis model. In addition to the Th1/Th2/Th17 pathway and NF-κB pathway, ER stress was shown to be involved in mitigating inflammation and decreasing apoptosis. Thus, ER stress is a new aspect in elucidating the relationship between helminth infection and inflammatory bowel disease (IBD), which may offer new therapeutic methods for IBD.

Keywords: Endoplasmic reticulum stress, Schistosoma japonicum, Colitis

Core tip:Schistosoma (S.) japonicum has been demonstrated to participate in the development of colitis in animal experiments as well as clinical trials. However, the effects of Schistosoma infection on colitis and the underlying mechanism are still elusive. Here, we studied the effects of exposure to S. japonicum cercariae on dextran sodium sulfate (DSS)-induced colitis. We found that S. japonicum attenuated DSS-induced colitis in mice by reducing inflammatory response and apoptosis in colon tissues. Besides Th1/Th2/Th17 pathway and nuclear factor-kappa B pathway, endoplasmic reticulum stress played an important role in the preventive effects of parasite infection on DSS-induced colitis.