Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2016; 22(43): 9515-9524
Published online Nov 21, 2016. doi: 10.3748/wjg.v22.i43.9515
Anti-inflammatory effect of cannabinoid agonist WIN55, 212 on mouse experimental colitis is related to inhibition of p38MAPK
Ya-Jing Feng, Yong-Yu Li, Xu-Hong Lin, Kun Li, Ming-Hua Cao
Ya-Jing Feng, Yong-Yu Li, Xu-Hong Lin, Kun Li, Ming-Hua Cao, Department of Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China,
Ya-Jing Feng, Department of Center ICU, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Author contributions: Li YY designed the project; Feng YJ performed the experiments and analyzed the data; Lin XH, Li K and Cao MH contributed to performing the experiments and in data analysis; Feng YJ and Li YY wrote the paper.
Supported by the National Natural Science Foundation of China, No. 81400581 (to Feng YJ) and No. 81270477 (to Li YY).
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Department of Pathophysiology, Tongji University School of Medicine, China.
Institutional animal care and use committee statement: All experiments involving animals were reviewed and approved by the Animal Care and Use Committee of Tongji University (IACUC No. 2008-001).
Conflict-of-interest statement: We declare that the authors of this article do not have any conflict of interest.
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: Yong-Yu Li, MD, Department of Pathophysiology, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, China. liyongyu@tongji.edu.cn
Telephone: +86-21-65981021 Fax: +86-21-65987071
Received: June 22, 2016
Peer-review started: June 24, 2016
First decision: August 22, 2016
Revised: September 4, 2016
Accepted: September 28, 2016
Article in press: September 28, 2016
Published online: November 21, 2016
Processing time: 148 Days and 16.6 Hours
Abstract
AIM

To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid (CB) receptors, WIN55-212-2 (WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future.

METHODS

We established the colitis model in C57BL/6 mice by replacing the animals’ water supply with 4% dextran sulfate sodium (DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion. The plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the myeloperoxidase (MPO) activity in colon tissue were measured. The expressions of cannabinoid receptors, claudin-1 protein, p38 mitogen-activated protein kinase (p38MAPK) and its phosphorylated form (p-p38) in colon tissue were determined by immunohistochemistry and Western blot. In addition, the effect of SB203580 (SB), an inhibitor of p38, was investigated in parallel experiments, and the data were compared with those from intervention groups of WIN55 and SB alone or used together.

RESULTS

The results demonstrated that WIN55 or SB treatment alone or together improved the pathological changes in mice with DSS colitis, decreased the plasma levels of TNF-α, and IL-6, and MPO activity in colon. The enhanced expression of claudin-1 and the inhibited expression of p-p38 in colon tissues were found in the WIN55-treated group. Besides, the expression of CB1 and CB2 receptors was enhanced in the colon after the induction of DSS colitis, but reduced when p38MAPK was inhibited.

CONCLUSION

These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38MAPK. Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38MAPK signaling pathway and the endogenous CB system.

Keywords: Inflammatory bowel disease; Endogenous cannabinoid system; p38MAPK; Experimental colitis; Claudin-1

Core tip: Inflammatory bowel disease demands more effective therapies, and cannabinoids are beneficial in alleviating inflammation in some diseases. In this study, we reported the anti-inflammatory effect and protective role of WIN55-212-2, an agonist of cannabinoid receptors, on the mice with dextran sulfate sodium-induced experimental colitis, and revealed that this agent exerts its action at least partially by inhibiting p38 mitogen-activated protein kinase.