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Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model

Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inf...

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Autores principales: Lv, Qing-Kang, Liu, Ju-Xiong, Li, Su-Nan, Gao, Ying-Jie, Lv, Yan, Xu, Zi-Peng, Huang, Bing-Xu, Xu, Shi-Yao, Yang, Dong-Xue, Zeng, Ya-Long, Liu, Dian-Feng, Wang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661844/
https://www.ncbi.nlm.nih.gov/pubmed/26561804
http://dx.doi.org/10.3390/ijms161125985
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author Lv, Qing-Kang
Liu, Ju-Xiong
Li, Su-Nan
Gao, Ying-Jie
Lv, Yan
Xu, Zi-Peng
Huang, Bing-Xu
Xu, Shi-Yao
Yang, Dong-Xue
Zeng, Ya-Long
Liu, Dian-Feng
Wang, Wei
author_facet Lv, Qing-Kang
Liu, Ju-Xiong
Li, Su-Nan
Gao, Ying-Jie
Lv, Yan
Xu, Zi-Peng
Huang, Bing-Xu
Xu, Shi-Yao
Yang, Dong-Xue
Zeng, Ya-Long
Liu, Dian-Feng
Wang, Wei
author_sort Lv, Qing-Kang
collection PubMed
description Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn’s disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1β in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1β were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.
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spelling pubmed-46618442015-12-10 Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model Lv, Qing-Kang Liu, Ju-Xiong Li, Su-Nan Gao, Ying-Jie Lv, Yan Xu, Zi-Peng Huang, Bing-Xu Xu, Shi-Yao Yang, Dong-Xue Zeng, Ya-Long Liu, Dian-Feng Wang, Wei Int J Mol Sci Article Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn’s disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1β in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1β were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells. MDPI 2015-11-06 /pmc/articles/PMC4661844/ /pubmed/26561804 http://dx.doi.org/10.3390/ijms161125985 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lv, Qing-Kang
Liu, Ju-Xiong
Li, Su-Nan
Gao, Ying-Jie
Lv, Yan
Xu, Zi-Peng
Huang, Bing-Xu
Xu, Shi-Yao
Yang, Dong-Xue
Zeng, Ya-Long
Liu, Dian-Feng
Wang, Wei
Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model
title Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model
title_full Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model
title_fullStr Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model
title_full_unstemmed Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model
title_short Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn’s Disease Mouse Model
title_sort mycophenolate mofetil modulates differentiation of th1/th2 and the secretion of cytokines in an active crohn’s disease mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661844/
https://www.ncbi.nlm.nih.gov/pubmed/26561804
http://dx.doi.org/10.3390/ijms161125985
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