DDS: 同型半胱氨酸会促进CD4+T细胞向Th17细胞分化

2018-07-22 MedSci MedSci原创

患者出现高同型半胱氨酸血症(Hhcy)是在炎性肠病(IBD)患者中观察到的常见现象。之前的研究表明,Hhcy在结肠炎动物模型中加重了肠道炎症。在具有Hhcy的结肠炎动物模型中也观察到IL-17和RORγt水平增加。然而,还未有研究报道过高半胱氨酸对Th17细胞分化的直接影响。本研究的目的是验证Hhcy对CD4+T细胞分化为Th17细胞具有影响作用。

背景
患者出现高同型半胱氨酸血症(Hhcy)是在炎性肠病(IBD)患者中观察到的常见现象。之前的研究表明,Hhcy在结肠炎动物模型中加重了肠道炎症。在具有Hhcy的结肠炎动物模型中也观察到IL-17和RORγt水平增加。然而,还未有研究报道过高半胱氨酸对Th17细胞分化的直接影响。本研究的目的是验证Hhcy对CD4+T细胞分化为Th17细胞具有影响作用。

方法
研究人员从Wistar大鼠结肠粘膜中的分理出固有层淋巴细胞(LPL)并在Th17诱导(iTH17)环境下培养。不同浓度的Hcy(0-100μmol/ ml)与IL-23(100ng / ml)或叶酸(5μmol/ ml)进行不同的组合。LPL分为以下八组:(1)对照组;(2)10μmol/ ml Hcy;(3)25μmol/ ml Hcy;(4)50μmol/ ml Hcy;(5)100μmol/ ml Hcy;(6)100ng / ml IL-23组;(7)50μmol/ ml Hcy + 100ng / ml IL-23组和(8)50μmol/ ml Hcy + 100ng / ml IL-23 +5μmol/ ml叶酸组。通过免疫印迹分析检测IL-17,类视黄醇相关的孤儿核受体-γt(RORγt),p38MAPK,磷酸化的p38MAPK,胞质磷脂酶A2(cPLA2),磷酸化的cPLA2和环加氧酶2(COX2)的蛋白质表达水平。同时将T细胞通过流式细胞术分析。

结果
Hcy可以增加IL-17的蛋白质水平,可以提高磷酸化的cPLA2与cPLA2(p-cPLA2 / cPLA2)和COX2的比率,存在剂量依赖性效能。50μmol/ ml的Hcy是增加这些分子的蛋白质水平的最佳浓度。在Hhcy组中,细胞培养上清液中IL-17和PGE2的水平以及IL-17和RORγt在阳性CD4+T细胞中的表达也增加。IL-23与Hcy显示出对CD4+Th细胞分化为Th17细胞的协同作用,而叶酸补充显示出抑制作用。

结论
同型半胱氨酸以剂量依赖性方式促进CD4+T细胞向Th17细胞的分化,而叶酸可以抑制这种效果。

原始出处:
Xin Gao.et al.Effect of Homocysteine on the Differentiation of CD4+T Cells into Th17 Cells. Digestive Diseases and Sciences. 2018.

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    2018-10-14 qidongfanjian
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    2019-03-30 xuyu
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    2018-07-24 zhaojie88
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    2018-07-23 大爰

    学习了谢谢分享!!

    0

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    2018-07-23 1e145228m78(暂无匿称)

    学习了,谢谢作者分享!

    0

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    2018-07-23 kafei

    了解一下谢谢

    0