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2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation

The immunosuppressive function of mesenchymal stem cells (MSCs) is well known. Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is widely expressed in several cells and is involved in various physiological and pathological processes. Previously, we found that the expre...

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Autores principales: Zhang, Guorui, Li, Xiaoming, Cheng, Yi, Yu, Haiyang, Gu, Wen, Cui, Zhilei, Guo, Xuejun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717173/
https://www.ncbi.nlm.nih.gov/pubmed/31385165
http://dx.doi.org/10.1007/s11626-019-00383-y
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author Zhang, Guorui
Li, Xiaoming
Cheng, Yi
Yu, Haiyang
Gu, Wen
Cui, Zhilei
Guo, Xuejun
author_facet Zhang, Guorui
Li, Xiaoming
Cheng, Yi
Yu, Haiyang
Gu, Wen
Cui, Zhilei
Guo, Xuejun
author_sort Zhang, Guorui
collection PubMed
description The immunosuppressive function of mesenchymal stem cells (MSCs) is well known. Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is widely expressed in several cells and is involved in various physiological and pathological processes. Previously, we found that the expression of AhR was downregulated in MSCs isolated from mice with neutrophilic asthma and that the activation of AhR enhanced the function of MSCs to alleviate neutrophilic asthma. We hypothesized that AhR activation enhanced MSCs for their immunosuppressive function. We aimed to investigate whether AhR activation can augment the suppressive function of MSCs against splenocyte proliferation. We co-cultured MSCs or AhR-activated MSCs with splenocytes at different ratios. The results showed that AhR activation in MSCs upregulated the expression of inducible nitric oxide (iNOS), which promoted the production of nitric oxide (NO), thus enhancing the inhibitory effect on splenocyte proliferation. The NO donor S-nitroso-N-acetylpenicillamine also inhibited the proliferation of splenocytes, and the iNOS inhibitor N(G)-nitro L-arginine methyl ester and NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide partially reversed the immunosuppressive function. Our study indicates that the AhR activation of MSCs might have an important role in the regulation of splenocyte proliferation and might serve as a potential strategy for treating immune-related diseases.
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spelling pubmed-67171732019-09-13 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation Zhang, Guorui Li, Xiaoming Cheng, Yi Yu, Haiyang Gu, Wen Cui, Zhilei Guo, Xuejun In Vitro Cell Dev Biol Anim Article The immunosuppressive function of mesenchymal stem cells (MSCs) is well known. Aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family, is widely expressed in several cells and is involved in various physiological and pathological processes. Previously, we found that the expression of AhR was downregulated in MSCs isolated from mice with neutrophilic asthma and that the activation of AhR enhanced the function of MSCs to alleviate neutrophilic asthma. We hypothesized that AhR activation enhanced MSCs for their immunosuppressive function. We aimed to investigate whether AhR activation can augment the suppressive function of MSCs against splenocyte proliferation. We co-cultured MSCs or AhR-activated MSCs with splenocytes at different ratios. The results showed that AhR activation in MSCs upregulated the expression of inducible nitric oxide (iNOS), which promoted the production of nitric oxide (NO), thus enhancing the inhibitory effect on splenocyte proliferation. The NO donor S-nitroso-N-acetylpenicillamine also inhibited the proliferation of splenocytes, and the iNOS inhibitor N(G)-nitro L-arginine methyl ester and NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide partially reversed the immunosuppressive function. Our study indicates that the AhR activation of MSCs might have an important role in the regulation of splenocyte proliferation and might serve as a potential strategy for treating immune-related diseases. Springer US 2019-08-05 2019 /pmc/articles/PMC6717173/ /pubmed/31385165 http://dx.doi.org/10.1007/s11626-019-00383-y Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Zhang, Guorui
Li, Xiaoming
Cheng, Yi
Yu, Haiyang
Gu, Wen
Cui, Zhilei
Guo, Xuejun
2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation
title 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation
title_full 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation
title_fullStr 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation
title_full_unstemmed 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation
title_short 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation
title_sort 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717173/
https://www.ncbi.nlm.nih.gov/pubmed/31385165
http://dx.doi.org/10.1007/s11626-019-00383-y
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