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Immethridine, histamine H(3)-receptor (H(3)R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells

Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is the preferential experimental rodent model for MS. Previous study demonstrated histamine...

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Autores principales: Shi, Yaru, Li, Zhenlong, Chen, Ran, Zhang, Jiang, Hu, Xuefei, He, Cong, Su, Qiong, Ma, Hongdou, Ren, Hua, Qian, Min, Cui, Shufang, Jiang, Wenzheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650398/
https://www.ncbi.nlm.nih.gov/pubmed/29088843
http://dx.doi.org/10.18632/oncotarget.20500
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author Shi, Yaru
Li, Zhenlong
Chen, Ran
Zhang, Jiang
Hu, Xuefei
He, Cong
Su, Qiong
Ma, Hongdou
Ren, Hua
Qian, Min
Cui, Shufang
Jiang, Wenzheng
author_facet Shi, Yaru
Li, Zhenlong
Chen, Ran
Zhang, Jiang
Hu, Xuefei
He, Cong
Su, Qiong
Ma, Hongdou
Ren, Hua
Qian, Min
Cui, Shufang
Jiang, Wenzheng
author_sort Shi, Yaru
collection PubMed
description Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is the preferential experimental rodent model for MS. Previous study demonstrated histamine H3 receptor (H3R) was an important factor in pathophysiology of EAE and immethridine was the most selective agonist of H3R. However, whether immethridine has therapeutic effect on EAE and its mechanism remained to be defined. Here we constructed EAE mouse model by immunization of MOG(35-55) peptides with complete Freund’s adjuvant, immethridine was used to treat EAE and its therapeutic effect was evaluated. The results showed that the treatment of immethridine could alleviate EAE. The percentage of Th1 and Th17 in the spleen from the treated EAE mice decreased and the surface molecules such as CD40, CD86 or MHCII on dendritic cells (DCs) were also down-regulated. To understand the effect of immethridine on DCs, bone marrow-derived DCs were prepared and the immunological functions were analyzed. The data demonstrated that immethridine could change the expression profiles of cytokines in DCs and inhibit the expression of the co-stimulatory molecules such as CD40 and CD86. Furthermore, immethridine also inhibited the antigen-presenting function of DCs and T cell differentiation induced by DCs. Signaling pathway analysis demonstrated that the phosphorylation of NF-κB p65 but not ERK1/2 in DCs was inhibited after the treatment of immethridine. These data strongly suggested that immethridine could inhibit the function of DCs and indicated the therapeutic potential on EAE.
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spelling pubmed-56503982017-10-30 Immethridine, histamine H(3)-receptor (H(3)R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells Shi, Yaru Li, Zhenlong Chen, Ran Zhang, Jiang Hu, Xuefei He, Cong Su, Qiong Ma, Hongdou Ren, Hua Qian, Min Cui, Shufang Jiang, Wenzheng Oncotarget Research Paper Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is the preferential experimental rodent model for MS. Previous study demonstrated histamine H3 receptor (H3R) was an important factor in pathophysiology of EAE and immethridine was the most selective agonist of H3R. However, whether immethridine has therapeutic effect on EAE and its mechanism remained to be defined. Here we constructed EAE mouse model by immunization of MOG(35-55) peptides with complete Freund’s adjuvant, immethridine was used to treat EAE and its therapeutic effect was evaluated. The results showed that the treatment of immethridine could alleviate EAE. The percentage of Th1 and Th17 in the spleen from the treated EAE mice decreased and the surface molecules such as CD40, CD86 or MHCII on dendritic cells (DCs) were also down-regulated. To understand the effect of immethridine on DCs, bone marrow-derived DCs were prepared and the immunological functions were analyzed. The data demonstrated that immethridine could change the expression profiles of cytokines in DCs and inhibit the expression of the co-stimulatory molecules such as CD40 and CD86. Furthermore, immethridine also inhibited the antigen-presenting function of DCs and T cell differentiation induced by DCs. Signaling pathway analysis demonstrated that the phosphorylation of NF-κB p65 but not ERK1/2 in DCs was inhibited after the treatment of immethridine. These data strongly suggested that immethridine could inhibit the function of DCs and indicated the therapeutic potential on EAE. Impact Journals LLC 2017-08-24 /pmc/articles/PMC5650398/ /pubmed/29088843 http://dx.doi.org/10.18632/oncotarget.20500 Text en Copyright: © 2017 Shi et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Shi, Yaru
Li, Zhenlong
Chen, Ran
Zhang, Jiang
Hu, Xuefei
He, Cong
Su, Qiong
Ma, Hongdou
Ren, Hua
Qian, Min
Cui, Shufang
Jiang, Wenzheng
Immethridine, histamine H(3)-receptor (H(3)R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells
title Immethridine, histamine H(3)-receptor (H(3)R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells
title_full Immethridine, histamine H(3)-receptor (H(3)R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells
title_fullStr Immethridine, histamine H(3)-receptor (H(3)R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells
title_full_unstemmed Immethridine, histamine H(3)-receptor (H(3)R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells
title_short Immethridine, histamine H(3)-receptor (H(3)R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells
title_sort immethridine, histamine h(3)-receptor (h(3)r) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650398/
https://www.ncbi.nlm.nih.gov/pubmed/29088843
http://dx.doi.org/10.18632/oncotarget.20500
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