©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Sodium chloride exacerbates dextran sulfate sodium-induced colitis by tuning proinflammatory and antiinflammatory lamina propria mononuclear cells through p38/MAPK pathway in mice
Hong-Xia Guo, Nan Ye, Ping Yan, Min-Yue Qiu, Ji Zhang, Zi-Gang Shen, Hai-Yang He, Zhi-Qiang Tian, Hong-Li Li, Jin-Tao Li
Hong-Xia Guo, Jin-Tao Li, Department of Microbiology, Third Military Medical University (Army Medical University), District Shapingba, Chongqing 400038, China
Hong-Xia Guo, Nan Ye, Min-Yue Qiu, Jin-Tao Li, Institute of Tropical Medicine, Third Military Medical University (Army Medical University), District Shapingba, Chongqing 400038, China
Ping Yan, Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
Ji Zhang, Zi-Gang Shen, Hai-Yang He, Zhi-Qiang Tian, Institute of Immunology, Third Military Medical University (Army Medical University), District Shapingba, Chongqing 400038, China
Hong-Li Li, Department of Histology and Embryology, College of Basic Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China
Author contributions: Li JT designed the research; Guo HX, Ye N, Li HL and Qiu MY performed the research; Yan P, Zhang J, Shen ZG, He HY and Tian ZQ contributed reagents and analytic tools; Ye N contributed to the statistical analysis; Guo HX and Li JT wrote the manuscript and carried out the critical revision of the manuscript; all authors provided final approval of the article.
Supported by National Natural Science Foundation of China, No. 81271813 and No. 81570497.
Institutional review board statement: This study was reviewed and approved by the Third Military Medical University (Army Medical University) Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving the care and use of animals were approved by The Institutional Animal Care and Use Committee of the Third Military Medical University (Army Medical University).
Conflict-of-interest statement: All authors declared there were no conflicts of interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Jin-Tao Li, PhD, Professor, Institute of Tropical Medicine, Third Military Medical University (Army Medical University), Gaotanyan Street 30, Chongqing 400038, China. firstname.lastname@example.org
Telephone: +86-23-68752329 Fax: +86-23-68752329
Received: January 25, 2018
Peer-review started: January 26, 2018
First decision: February 24, 2018
Revised: March 11, 2018
Accepted: March 18, 2018
Article in press: March 18, 2018
Published online: April 28, 2018
To investigate the influence of high salt on dextran sulfate sodium (DSS)-induced colitis in mice and explore the underlying mechanisms of this effect.
DSS and NaCl were used to establish the proinflammatory animal model. We evaluated the colitis severity. Flow cytometry was employed for detecting the frequencies of Th1, macrophages and Tregs in spleen, mesenteric lymph node and lamina propria. The important role of macrophages in the promotion of DSS-induced colitis by NaCl was evaluated by depleting macrophages with clodronate liposomes. Activated peritoneal macrophages and lamina propria mononuclear cells (LPMCs) were stimulated with NaCl, and proteins were detected by western blotting. Cytokines and inflammation genes were analyzed by enzyme-linked immunosorbent assay and RT-PCR, respectively.
The study findings indicate that NaCl up-regulates the frequencies of CD11b+ macrophages and CD4+IFN-γ+IL-17+ T cells in lamina propria in DSS-treated mice. CD3+CD4+CD25+Foxp3+ T cells, which can secrete high levels of IL-10 and TGF-β, increase through feedback in NaCl- and DSS-treated mice. Furthermore, clodronate liposomes pretreatment significantly alleviated DSS-induced colitis, indicating that macrophages play a vital role in NaCl proinflammatory activity. NaCl aggravates peritoneal macrophage inflammation by promoting the expressions of interleukin (IL)-1, IL-6 and mouse inducible nitric oxide synthase. Specifically, high NaCl concentrations promote p38 phosphorylation in lipopolysaccharide- and IFN-γ-activated LPMCs mediated by SGK1.
Proinflammatory macrophages may play an essential role in the onset and development of NaCl-promoted inflammation in DSS-induced colitis. The underlining mechanism involves up-regulation of the p38/MAPK axis.
Core tip: NaCl, as an indispensable environmental factor, evokes both innate and adaptive immune proinflammation cell activation in mice affected by dextran sulfate sodium (DSS)-induced colitis. Proinflammatory CD4+ cells in DSS- and NaCl-treated mice are mainly double-positive IL-17+IFN-γ+ T cells. Macrophage depletion significantly alleviates DSS-induced colitis. M1 macrophages play an important role in the proinflammatory effect of NaCl in the mouse gut. NaCl promotes M1 proinflammatory gene expression in lipopolysaccharide-activated peritoneal macrophage. The mechanism by which NaCl promotes DSS-induced colitis involves up-regulation of the p38/MAPK axis.