Maresin 1 alleviates dextran sulfate sodium-induced ulcerative colitis by regulating NRF2 and TLR4/NF-kB signaling pathway.

Abstract

OBJECTIVE:

Ulcerative colitis (UC) is one of the most common gastrointestinal diseases, characterized as a chronic, relapsing inflammation that causes damage to the colonic mucosa. Maresin 1 (MaR1), a specialized proresolving mediator, has powerful anti-inflammatory activity that prevents the occurrence of various inflammatory diseases. The aim of this study was to explore the role and potential mechanism of MaR1 in DSS-induced ulcerative colitis.

METHODS:

In the present study, we established dextran sulfate sodium (DSS)-induced ulcerative colitis rat model in vivo. Rats with colitis received tail vein injection of MaR1, with or without intraperitoneal injection of ML385. The changes of body weight, colon length, disease activity index (DAI), colonic histopathology, inflammatory cytokines, the activity of myeloperoxidase (MPO) and reactive oxygen species (ROS), and infiltration of macrophages expressing F4/80 were analyzed for the evaluation of colitis severity. In addition, protein expressions were detected using western blot.

RESULTS:

MaR1 significantly reduced inflammatory cytokines production, and restored body weight, DAI and colonic histopathology. Besides, MaR1 improved the expression of tight junction (TJ) proteins and reduced the infiltration of neutrophil and macrophages, as well as a decreased activity of MPO and ROS. Meanwhile, MaR1 activated Nrf2 signaling and decreased toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) activation. Furthermore, ML385, an inhibitor of Nrf2, significantly reversed the protective effect of MaR1.

CONCLUSION:

MaR1 play a protective role in DSS-induced colitis by activating Nrf2 signaling and inactivating Nrf2-mediated TLR4/NF-κB signaling pathway, which mediate proinflammatory mediators and intestinal TJ proteins in rats, providing novel insights into the therapeutic strategy of colitis.

• Authors: Shujin Qiu, Ping Li, Hengfang Zhao, Xiaofang Li
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 78 Pg. 106018 (Jan 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 31780371 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• 7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, rat
• Protective Agents
• Reactive Oxygen Species
• Tight Junction Proteins
• Tlr4 protein, rat
• Toll-Like Receptor 4
• Docosahexaenoic Acids
• Dextran Sulfate

Topics

• Animals
• Colitis, Ulcerative (chemically induced, drug therapy, immunology, pathology)
• Colon (cytology, drug effects, immunology, pathology)
• Dextran Sulfate (toxicity)
• Disease Models, Animal
• Docosahexaenoic Acids (pharmacology, therapeutic use)
• Humans
• Intestinal Mucosa (cytology, drug effects, immunology, pathology)
• Macrophages (drug effects, immunology)
• Male
• NF-E2-Related Factor 2 (antagonists & inhibitors, metabolism)
• NF-kappa B (metabolism)
• Neutrophils (drug effects, immunology)
• Protective Agents (pharmacology, therapeutic use)
• Rats
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects, immunology)
• Tight Junction Proteins (metabolism)
• Toll-Like Receptor 4 (metabolism)