Effect of exogenous galectin-9, a natural TIM-3 ligand, on the severity of TNBS- and DSS-induced colitis in mice.

Abstract

Inflammatory bowel disease (IBD) have a complex pathogenesis that is yet to be completely understood. However, a strong correlation between Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling and IBD has been observed. T-cell immunoglobulin and mucin domain-containing-3 (Tim-3) has been reported to regulate TLR4/NF-κB by interacting with Galectin-9 (Gal-9), and recombinant Gal-9 can activate Tim-3; however, its potential properties in IBD and the underlying mechanism remain unclear. This study aimed to determine how Gal-9 affects experimental colitis in mice. Dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) were used to establish colitis in mice, and the severity of the illness was assessed based on body weight, colon length, and histology. Therefore, we explored the effects of Gal-9 treatment on colitis. Furthermore, we analyzed the effect of Gal-9 on the expression of Tim-3 and TLR4/NF-κB pathway in colonic tissues and the serum levels of interferon-gamma (IFN-γ), interleukin (IL)-1β, and IL-6. Tim-3 expression in the colon was notably decreased in mice with TNBS-induced colitis, whereas TLR4/NF-kB expression was significantly increased. Intraperitoneal injection of Gal-9 dramatically decreased the disease activity index and attenuated the level of intestinal mucosal inflammation in TNBS-induced colitis mice (p < 0.05). Intraperitoneal administration of Gal-9 significantly increased Tim-3 expression in the colon and decreased the serum concentrations of IFN-γ, IL-1β, and IL-6. Additionally, Gal-9 treatment significantly downregulated the expression of TLR4 signaling pathway-related proteins. In contrast, Gal-9 did not reduce the severity of DSS-induced colitis. In summary, exogenous Gal-9 increased Tim-3 expression, inhibited the TLR4/NF-κB pathway, and alleviated TNBS-induced colitis in mice but not DSS-induced colitis in mice, revealing its potential therapeutic ramifications for IBD.

• Authors: Huifang Xiong, Guohui Xue, Yuting Zhang, Shuang Wu, Qiaoyun Zhao, Rulin Zhao, Nanjin Zhou, Yong Xie
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 115 Pg. 109645 (Feb 2023) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 36610329 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• NF-kappa B
• Toll-Like Receptor 4
• Interleukin-6
• Hepatitis A Virus Cellular Receptor 2
• Trinitrobenzenesulfonic Acid
• Ligands
• Galectins
• Dextran Sulfate

Topics

• Mice
• Animals
• NF-kappa B (metabolism)
• Toll-Like Receptor 4 (metabolism)
• Interleukin-6 (therapeutic use)
• Hepatitis A Virus Cellular Receptor 2
• Trinitrobenzenesulfonic Acid
• Ligands
• Colitis (chemically induced, drug therapy, metabolism)
• Inflammatory Bowel Diseases
• Galectins (therapeutic use)
• Dextran Sulfate
• Disease Models, Animal
• Mice, Inbred C57BL