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Maackiain, a compound derived from Sophora flavescens, increases IL-1β production by amplifying nigericin-mediated inflammasome activation.
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-06-26 , DOI: 10.1002/2211-5463.12899
Jin-Won Huh 1 , Jung-Hoon Lee 1 , Eekhyoung Jeon 1 , Hyung Won Ryu 2 , Sei-Ryang Oh 2 , Kyung-Seop Ahn 2 , Hyun Sik Jun 1 , Un-Hwan Ha 1
Affiliation  

Sophora flavescens is used as a traditional herbal medicine to modulate inflammatory responses. However, little is known about the impact of (‐)‐maackiain, a compound derived from S. flavescens, on the activation of inflammasome/caspase‐1, a key factor in interleukin‐1β (IL‐1β) processing. Here, we report that (‐)‐maackiain potently amplified caspase‐1 cleavage in macrophages in response to nigericin (Nig). In macrophages primed with either lipopolysaccharide or monophosphoryl lipid A, Nig‐mediated caspase‐1 cleavage was also markedly promoted by (‐)‐maackiain. Notably, (‐)‐maackiain induced the production of vimentin, an essential mediator for the activation of the NOD‐, LRR‐, and pyrin domain‐containing protein 3 inflammasome, thereby contributing to promotion of the formation of the inflammasome complex to activate caspase‐1. Taken together, our data suggest that (‐)‐maackiain exerts an immunostimulatory effect by promoting IL‐1β production via activation of the inflammasome/caspase‐1 pathway. Thus, the potent inflammasome‐activating effect of (‐)‐maackiain may be clinically useful as an acute immune‐stimulating agent.

中文翻译:

Maackiain 是一种源自苦参的化合物,通过放大尼日利亚菌素介导的炎症小体激活来增加 IL-1β 的产生。

苦参被用作传统草药来调节炎症反应。然而,关于 (-)-maackiain(一种源自S. flavescens的化合物)的影响知之甚少,关于炎症小体/caspase-1 的激活,这是白细胞介素-1β (IL-1β) 加工的关键因素。在这里,我们报告了 (-)-maackiain 响应尼日利亚菌素 (Nig) 在巨噬细胞中有效放大 caspase-1 裂解。在用脂多糖或单磷酰脂质 A 引发的巨噬细胞中,(-)-maackiain 也显着促进了 Nig 介导的 caspase-1 裂解。值得注意的是,(-)-maackiain 诱导波形蛋白的产生,波形蛋白是激活包含 NOD-、LRR-和pyrin 结构域的蛋白 3 炎性体的必需介质,从而有助于促进炎性体复合物的形成以激活半胱天冬酶‐1. 总之,我们的数据表明,(-)-maackiain 通过激活炎症小体/caspase-1 通路促进 IL-1β 的产生,从而发挥免疫刺激作用。因此,
更新日期:2020-06-26
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