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Int Immunopharmacol. 2015 May;26(1):221-8. doi: 10.1016/j.intimp.2015.03.033. Epub 2015 Apr 6.

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

Author information

1
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China. Electronic address: zhj880616@163.com.
2
The Center of Diagnosis and Treatment for Joint Disease, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, China. Electronic address: sunye@163.com.
3
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, China. Electronic address: shipeiliang@163.com.
4
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China. Electronic address: dongjianning@163.com.
5
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China. Electronic address: zuolugen@163.com.
6
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China. Electronic address: whonggang@163.com.
7
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China. Electronic address: gongjf03@163.com.
8
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China. Electronic address: liyi13@163.com.
9
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China. Electronic address: liligu@163.com.
10
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China. Electronic address: lining@163.com.
11
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China. Electronic address: lijieshou@163.com.
12
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 Jiangsu, China. Electronic address: zhuweimingtg@163.com.

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.

KEYWORDS:

Autophagy; Celastrol; Colitis; Inflammation

PMID:
25858875
DOI:
10.1016/j.intimp.2015.03.033
[Indexed for MEDLINE]

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