2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation
2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced aryl hydrocarbon receptor activation enhanced the suppressive function of mesenchymal stem cells against splenocyte proliferation
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2,3,7,8-四氯二苯并-对二恶英诱导的芳烃受体激活增强间充质干细胞对脾细胞增殖的抑制功能
DOI：
10.1007/s11626-019-00383-y
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发表时间：
2019-08
影响因子：
2.1
通讯作者：
Guo Xuejun
中科院分区：
文献类型：
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作者：
Zhang Guorui;Li Xiaoming;Cheng Yi;Yu Haiyang;Gu Wen;Cui Zhilei;Guo Xuejun
间充质干细胞（MSCs）的免疫抑制功能是众所周知的。芳烃受体（Aryl hydrocarbon receptor, AhR）是bHLH/PAS家族的一种转录因子，广泛表达于多种细胞中，参与多种生理病理过程。先前，我们发现从嗜中性粒细胞哮喘小鼠分离的MSCs中AhR的表达下调，并且AhR的激活增强了MSCs减轻嗜中性粒细胞哮喘的功能。我们假设AhR激活增强了MSCs的免疫抑制功能。我们的目的是研究AhR激活是否可以增强MSCs对脾细胞增殖的抑制功能。我们将MSCs或ahr活化的MSCs与脾细胞按不同比例共培养。结果表明，在MSCs中激活AhR可上调诱导型一氧化氮（iNOS）的表达，促进一氧化氮（NO）的产生，从而增强对脾细胞增殖的抑制作用。NO供体s -亚硝基-N-乙酰青霉胺也能抑制脾细胞的增殖，iNOS抑制剂N(G)-硝基- l-精氨酸甲酯和NO清除剂2-苯基-4,4,5,5-四甲基咪唑啉-1-氧基- 3-氧化物部分逆转免疫抑制功能。我们的研究表明，MSCs的AhR激活可能在调节脾细胞增殖中起重要作用，并可能作为治疗免疫相关疾病的潜在策略。
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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影响因子：
20.3
作者：
Sato, Kazuya;Ozaki, Katsutoshi;Ozawa, Keiya
通讯作者：
Ozawa, Keiya
影响因子：
12.4
作者：
通讯作者：
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影响因子：
7.8
作者：
Cella M;Colonna M
通讯作者：
Colonna M
DOI：
10.1002/stem.2353/abstract
发表时间：
2016
期刊：
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影响因子：
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作者：
김종석;신성재;조상래;차승빈
通讯作者：
김종석;신성재;조상래;차승빈
DOI：
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发表时间：
2004
期刊：
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影响因子：
--
作者：
通讯作者：
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