Laquinimod ameliorates spontaneous colitis in interleukin-10-gene-deficient mice with improved barrier function.

Abstract

BACKGROUND AND AIMS:

Crohn's disease is an autoimmune disease associated with imbalanced mucosal immunity, mediated with increased Th1 and Th17 cells. Laquinimod, an immunomodulatory drug, has shown efficacy in regulating the differentiation of T cells. The aim of the study was to investigate the therapeutic effect of laquinimod on spontaneous colitis in interleukin-10-gene-deficient mice, an animal model of Crohn's disease.

METHODS:

Male Il10(-/-) mice aged 16weeks in the laquinimod group were treated with laquinimod with distilled water at a dose of 25mg/kg by oral gavage, 3 times a week. Il10(-/-) mice in the IL-10-KO group and wild type mice received equal volume of phosphate buffered saline by oral gavage, 3 times a week. After 4weeks, mice were sacrificed for analysis. Severity of colitis, epithelial expression of T-cell-associated cytokines, expression and distribution of tight junction proteins in the lamina propria and NF-κB signaling pathway associated mRNA expression were measured at the end of the experiment.

RESULTS:

Laquinimod treatment ameliorated spontaneous colitis in Il10(-/-) mice, which was associated with decreased T-cell-associated pro-inflammatory cytokines. Increased expression and correct distribution of tight junction proteins (occludin and ZO-1) were found in Il10(-/-) mice treated with laquinimod. In addition, in mice treated with laquinimod, NF-κB signaling pathway associated mRNA in the colon was also downregulated.

CONCLUSIONS:

Our results indicated that laquinimod treatment ameliorates colitis in Il10(-/-) mice and improves intestinal barrier function, which may support a new therapeutic approach to Crohn's disease.

• Authors: Jing Sun, Xiao Shen, Jianning Dong, Jie Zhao, Lugen Zuo, Honggang Wang, Yi Li, Weiming Zhu, Jianfeng Gong, Jieshou Li
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 29 Issue 2 Pg. 423-432 (Dec 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 26603637 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• IL10 protein, mouse
• NF-kappa B
• Quinolones
• Interleukin-10
• laquinimod
• Leukocyte Common Antigens

Topics

• Animals
• Colitis (drug therapy, genetics)
• Crohn Disease (drug therapy, genetics)
• Cytokines (biosynthesis)
• Interleukin-10 (deficiency, genetics)
• Intestinal Mucosa (drug effects, metabolism)
• Leukocyte Common Antigens
• Lymphocyte Count
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NF-kappa B (genetics)
• Permeability
• Quinolones (therapeutic use)