Protective Effect of Thalidomide on 2,4,6-Trinitrobenzenesulfonic Acid-Induced Experimental Colitis in Rats via the Inhibition of T Helper 17 Cells

Objective. To observe the effects of thalidomide on 2,4,6-trinitrobenzenesulfonic acid- (TNBS-) induced experimental colitis in rats and to explore the possible mechanism of thalidomide in the treatment of CD. Methods. Forty SD rats were randomly assigned into a healthy control group and TNBS-induce...

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Main Authors: Ying Xie, Dandan Li, Xiaoshuang Luan, Shuang Jin, Bo Yan, Feng Tian
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Canadian Journal of Gastroenterology and Hepatology
Online Access:http://dx.doi.org/10.1155/2020/8861854
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author Ying Xie
Dandan Li
Xiaoshuang Luan
Shuang Jin
Bo Yan
Feng Tian
author_facet Ying Xie
Dandan Li
Xiaoshuang Luan
Shuang Jin
Bo Yan
Feng Tian
author_sort Ying Xie
collection DOAJ
description Objective. To observe the effects of thalidomide on 2,4,6-trinitrobenzenesulfonic acid- (TNBS-) induced experimental colitis in rats and to explore the possible mechanism of thalidomide in the treatment of CD. Methods. Forty SD rats were randomly assigned into a healthy control group and TNBS-induced colitis groups, including an untreated TNBS-induced colitis group, a low-dose thalidomide group, and a high-dose thalidomide group, with 10 rats in each. After 7 days, the disease activity index (DAI), colon macroscopic damage index (CMDI), and tissue damage index (TDI) were evaluated. The colonic protein and mRNA expression levels of interleukin-6 (IL-6), IL-17, IL-23, and retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt) were determined using immunohistochemistry, western blot, and qRT-PCR. Results. Relative to the untreated TNBS-induced colitis group, the DAI, CMDI, and TDI were all reduced following the administration of thalidomide. Analytical testing (immunohistochemistry, western blot, and qRT-PCR) shows that IL-6, IL-17, IL-23, and RORγt protein and mRNA expression levels were significantly reduced by thalidomide (p<0.05 for all) and that these levels were significantly lower in the high-dose thalidomide group than in the low-dose thalidomide group (p<0.05 for all). Conclusions. Thalidomide effectively alleviated the symptoms and intestinal inflammatory injury induced by TNBS in rats, the effect of which was dose-dependent. The underlying mechanism may be a reduction in the expression levels of IL-6, IL-17, IL-23, and RORγt in colonic tissue and then subsequent inhibition of the differentiation and function of Th17 cells, thus further alleviating the intestinal inflammatory response.
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spelling doaj-art-1ab9a306c4f94c6582c419c4cc1a70a62025-02-03T06:45:53ZengWileyCanadian Journal of Gastroenterology and Hepatology2291-27892291-27972020-01-01202010.1155/2020/88618548861854Protective Effect of Thalidomide on 2,4,6-Trinitrobenzenesulfonic Acid-Induced Experimental Colitis in Rats via the Inhibition of T Helper 17 CellsYing Xie0Dandan Li1Xiaoshuang Luan2Shuang Jin3Bo Yan4Feng Tian5Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, ChinaDepartment of Gastroenterology, General Hospital of Fushun Mining Bureau, Fushun 113000, ChinaDepartment of Gastroenterology, Dandong First Hospital, Dandong 118000, ChinaDepartment of Gastroenterology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, ChinaDepartment of Gastroenterology, The People’s Hospital of Liaoning Province, Shenyang 110000, ChinaDepartment of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, ChinaObjective. To observe the effects of thalidomide on 2,4,6-trinitrobenzenesulfonic acid- (TNBS-) induced experimental colitis in rats and to explore the possible mechanism of thalidomide in the treatment of CD. Methods. Forty SD rats were randomly assigned into a healthy control group and TNBS-induced colitis groups, including an untreated TNBS-induced colitis group, a low-dose thalidomide group, and a high-dose thalidomide group, with 10 rats in each. After 7 days, the disease activity index (DAI), colon macroscopic damage index (CMDI), and tissue damage index (TDI) were evaluated. The colonic protein and mRNA expression levels of interleukin-6 (IL-6), IL-17, IL-23, and retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt) were determined using immunohistochemistry, western blot, and qRT-PCR. Results. Relative to the untreated TNBS-induced colitis group, the DAI, CMDI, and TDI were all reduced following the administration of thalidomide. Analytical testing (immunohistochemistry, western blot, and qRT-PCR) shows that IL-6, IL-17, IL-23, and RORγt protein and mRNA expression levels were significantly reduced by thalidomide (p<0.05 for all) and that these levels were significantly lower in the high-dose thalidomide group than in the low-dose thalidomide group (p<0.05 for all). Conclusions. Thalidomide effectively alleviated the symptoms and intestinal inflammatory injury induced by TNBS in rats, the effect of which was dose-dependent. The underlying mechanism may be a reduction in the expression levels of IL-6, IL-17, IL-23, and RORγt in colonic tissue and then subsequent inhibition of the differentiation and function of Th17 cells, thus further alleviating the intestinal inflammatory response.http://dx.doi.org/10.1155/2020/8861854
spellingShingle Ying Xie
Dandan Li
Xiaoshuang Luan
Shuang Jin
Bo Yan
Feng Tian
Protective Effect of Thalidomide on 2,4,6-Trinitrobenzenesulfonic Acid-Induced Experimental Colitis in Rats via the Inhibition of T Helper 17 Cells
Canadian Journal of Gastroenterology and Hepatology
title Protective Effect of Thalidomide on 2,4,6-Trinitrobenzenesulfonic Acid-Induced Experimental Colitis in Rats via the Inhibition of T Helper 17 Cells
title_full Protective Effect of Thalidomide on 2,4,6-Trinitrobenzenesulfonic Acid-Induced Experimental Colitis in Rats via the Inhibition of T Helper 17 Cells
title_fullStr Protective Effect of Thalidomide on 2,4,6-Trinitrobenzenesulfonic Acid-Induced Experimental Colitis in Rats via the Inhibition of T Helper 17 Cells
title_full_unstemmed Protective Effect of Thalidomide on 2,4,6-Trinitrobenzenesulfonic Acid-Induced Experimental Colitis in Rats via the Inhibition of T Helper 17 Cells
title_short Protective Effect of Thalidomide on 2,4,6-Trinitrobenzenesulfonic Acid-Induced Experimental Colitis in Rats via the Inhibition of T Helper 17 Cells
title_sort protective effect of thalidomide on 2 4 6 trinitrobenzenesulfonic acid induced experimental colitis in rats via the inhibition of t helper 17 cells
url http://dx.doi.org/10.1155/2020/8861854
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