The innate immune system is a prerequisite for biophylactic ability, but its dysregulation can cause inflammatory and autoimmune diseases. To determine a safe method of controlling inflammatory reactions in the brain, we examined the effects of gnetin C, a natural resveratrol dimer, on C-C motif chemokine ligand 2 (CCL2) and CCL5 (pro-inflammatory chemokines) production observed after treatment with polyinosinic-polycytidylic acid [poly IC; a synthetic analog of dsRNA as a Toll-like receptor 3 (TRL3) ligand, 30 μg/mL] in cultured human astrocytoma U373MG and neuroblastoma SH-SY5Y cells. The addition of gnetin C (10 μM) to the media moderately reduced the CCL2 production and markedly suppressed CCL5 production in both cells. In the TLR3-interferon (IFN)-β-phosphorylated-STAT1 (signal transducer and activator of transcription protein 1)RIG-I (retinoic acid-inducible gene-I) pathway that mediates CCL2 and CCL5 production, gnetin C first inhibits IFN-β expression in SH-SY5Y cells and primarily inhibits STAT1 phosphorylation in U373MG cells. In any case, gnetin C attenuated the dsRNA-activated TLR3 signaling resulting in CCL2 and CCL5 production, thus, may be useful for controlling TLR3-mediated inflammation in the brain.

中文翻译：

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Gnetin C通过抑制Toll样受体3信号传导途径抑制双链RNA诱导的CC基序趋化因子配体2（CCL2）和CCL5的产生。

先天免疫系统是生物防御能力的先决条件，但其失调可引起炎症和自身免疫性疾病。为了确定控制脑部炎症反应的安全方法，我们检查了聚肌苷酸-丁二酸-丁二酸-丁二醇处理后观察到的天然nets白藜芦醇二聚体gnetin C对CC基序趋化因子配体2（CCL2）和CCL5（促炎性趋化因子）产生的影响。聚胞苷酸[poly IC; dsRNA的合成类似物作为Toll样受体3（TRL3）配体[30μg/ mL]在培养的人星形细胞瘤U373MG和成神经细胞瘤SH-SY5Y细胞中合成。向培养基中添加促胃泌素C（10μM）适度降低了两个细胞中CCL2的产生并显着抑制了CCL5的产生。在介导CCL2和CCL5产生的TLR3-干扰素（IFN）-β-磷酸化STAT1（信号转导和转录蛋白1激活子）RIG-I（视黄酸诱导基因-I）途径中，netnetin C首先抑制IFN- β在SH-SY5Y细胞中表达，并主要抑制U373MG细胞中的STAT1磷酸化。在任何情况下，netnetin C都会减弱dsRNA激活的TLR3信号传导，从而导致CCL2和CCL5的产生，因此对于控制TLR3介导的大脑炎症可能有用。