Elucidation of the inhibitory effect of hopeaphenol on polynosinic- polycytidylic acid-induced innate immunity activation in human cerebral microvascular endothelial cells
Elucidation of the inhibitory effect of hopeaphenol on polynosinic- polycytidylic acid-induced innate immunity activation in human cerebral microvascular endothelial cells
复制标题
阐明希望苯酚对聚肌苷-聚胞苷酸诱导的人脑微血管内皮细胞天然免疫激活的抑制作用
DOI：
10.1016/j.jphs.2022.04.011
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发表时间：
2022
影响因子：
3.5
通讯作者：
Imaizumi T
中科院分区：
文献类型：
--
作者：
Xu L;Yu Z;Uesaka Y;Kawaguchi S;Kikuchi H;Daitoku K;MInakawa M;MOtomura S;Furukawa KI;Oshima Y;Seya K;Imaizumi T
用于调节先天免疫系统的药物开发对于预防和治疗自身炎性和自身免疫性疾病是重要的。在这种情况下，我们研究了白藜芦醇衍生物对大脑炎症反应的影响。白藜芦醇以低聚物的形式存在于Vitisplants中，具有神经保护作用;然而，其对先天免疫的调节作用仍不清楚。我们研究了白藜芦醇四聚体（+）-藜芦酚及其衍生物对聚肌苷酸-聚胞苷酸（poly IC）诱导的人脑微血管内皮细胞系hCMEC/D3产生干扰素（IFN）-β和C-X-C基序趋化因子10（CXCL 10）的影响。（+）-Hopeaphenol（1-10 μM）不仅以剂量依赖性方式抑制poly IC诱导的CXCL 10的产生，还以剂量依赖性方式抑制维甲酸诱导基因I的产生，并通过抑制p65的磷酸化而非干扰素调节转录因子IRF 3的磷酸化，显著降低poly IC诱导的hCMEC/D3细胞IFN-β基因表达和蛋白释放。对接研究表明（+）-藜芦酚对p65具有高亲和力。这些结果表明，（+）-藜芦酚可以通过抑制转录因子NF-κ B的磷酸化来抑制聚IC/IFN-β/CXCL 10信号传导轴，从而调节先天免疫系统。
Drug development for regulating the innate immune system is important for the prevention and treatment of autoinflammatory and autoimmune diseases. In this context, we investigated the effect of resveratrol derivatives on the inflammatory reactions in the brain. Resveratrol, which can be found inVitisplants in the form of oligomers, exhibits neuroprotective effects; however, its regulatory effects on innate immunity are still unclear. We examined the effects of (+)-hopeaphenol, a resveratrol tetramer, and its derivatives on the polyinosinic–polycytidylic acid (poly IC)-induced production of interferon (IFN)-β and C-X-C motif chemokine 10 (CXCL10) in the cultured human cerebral microvascular endothelial cell line hCMEC/D3. (+)-Hopeaphenol (1–10 μM) inhibited the poly IC-induced production of not only CXCL10 but also retinoic acid-inducible gene-I in a dose-dependent manner and significantly reduced the poly IC-induced IFN-β gene expression and protein release from hCMEC/D3 cells by inhibiting the phosphorylation of p65 but not that of the interferon regulatory transcription factor IRF3. A docking study indicated a high affinity of (+)-hopeaphenol for p65. These results suggest that (+)-hopeaphenol can regulate the innate immune system by inhibiting the poly IC/IFN-β/CXCL10 signaling axis via suppression of the phosphorylation of the transcription factor NF-ĸB.