Celastrol ameliorates experimental colitis in IL-10 deficient mice via the up-regulation of autophagy.

Abstract

BACKGROUND:

Celastrol had been proved effective in the treatment for IBD, probably with the modulation of oxidative stress, inflammatory cytokines and intestinal homeostasis. This study was aimed to investigate whether celastrol could ameliorate the inflammation of IL-10 deficient mice, a murine model of Crohn's disease (CD) with the induction of autophagy.

MATERIAL AND METHODS:

The mice included were divided into four groups, ##WT group, IL-10(-/-) group, Cel group and Control group (celastrol+3-Methyladenine). Celastrol (2 mg/kg) treatment by gavage was administered to mice daily over one week. 3-Methyladenine (autophagy inhibitors) was administered at a dose of 30 mg/kg by intraperitoneal injection. The histological evaluation of the colon, tissue myeloperoxidase (MPO), and colon inflammation of mice in the four groups was evaluated and compared. Furthermore, the PI3K/Akt/mTOR pathway and the status of autophagy in intestine affected by celastrol were also assessed.

RESULTS:

The one-week administration of celastrol ameliorated established colitis in IL-10 deficient mice, associated with a reduction of marked histological inflammation, a decreased colon MPO concentration and suppression of colonic proinflammatory cytokine. Furthermore, the decreased neutrophil infiltration in proximal colon and improvement of inflammation in the Cel group was much more obvious than that in the Control group. The Western blotting analysis of the PI3K/Akt/mTOR pathway and autophagy showed that celastrol treatment up-regulated the autophagy of colon tissue by suppressing the PI3K/Akt/mTOR signaling pathway.

CONCLUSIONS:

Celastrol ameliorates experimental colitis in IL-10 deficient mice via the up-regulation of autophagy by suppressing the PI3K/Akt/mTOR signaling pathway.

• Authors: Jie Zhao, Ye Sun, Peiliang Shi, Jian-Ning Dong, Lu-Gen Zuo, Hong-Gang Wang, Jian-Feng Gong, Yi Li, Li-Li Gu, Ning Li, Jie-Shou Li, Wei-Ming Zhu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 26 Issue 1 Pg. 221-8 (May 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25858875 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• IL10 protein, mouse
• Pentacyclic Triterpenes
• Triterpenes
• Interleukin-10
• Peroxidase
• mTOR protein, mouse
• TOR Serine-Threonine Kinases
• celastrol

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, therapeutic use)
• Autophagy (drug effects)
• Blotting, Western
• Colon (drug effects, immunology, pathology)
• Crohn Disease (drug therapy, immunology, pathology)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Interleukin-10 (deficiency, genetics)
• Mice, Inbred C57BL
• Mice, Knockout
• Pentacyclic Triterpenes
• Peroxidase (metabolism)
• Real-Time Polymerase Chain Reaction
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (antagonists & inhibitors)
• Triterpenes (administration & dosage, therapeutic use)