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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2020-01-01
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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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institution | Kabale University |
issn | 2291-2789 2291-2797 |
language | English |
publishDate | 2020-01-01 |
publisher | Wiley |
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series | Canadian Journal of Gastroenterology and Hepatology |
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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