Comparative effects of schisandrin A, B, and C on Propionibacterium acnes-induced, NLRP3 inflammasome activation-mediated IL-1β secretion and pyroptosis
Comparative effects of schisandrin A, B, and C on Propionibacterium acnes-induced, NLRP3 inflammasome activation-mediated IL-1β secretion and pyroptosis
复制标题
DOI：
10.1016/j.biopha.2017.09.097
复制
发表时间：
2017-12-01
影响因子：
7.5
通讯作者：
Lu, Yanhua
中科院分区：
文献类型：
--
作者：
Guo, Miaomiao;An, Faliang;Lu, Yanhua
痤疮丙酸杆菌是与痤疮相关的常见病原体，也是各种外科感染的原因。五味子甲素（Schisandrin A）、五味子乙素（Schisandrin B）和五味子丙素（Schisandrin C）是五味子属植物北五味子的代表性木脂素。Baill.提取物，抑制痤疮丙酸杆菌诱导的炎症。然而，它们对痤疮丙酸杆菌诱导的IL-1 β分泌和由NLRP 3炎性小体激活介导的焦亡的作用仍然未知。在这项研究中，我们比较了五味子甲素、B和C（五味子甲素、五味子B和五味子C）对痤疮丙酸杆菌感染的THP-1细胞中IL-1 β分泌和细胞凋亡的影响。由于NLRP 3在痤疮丙酸杆菌介导的炎症和焦亡中起重要作用，我们还通过测量NLRP 3、活性半胱天冬酶-1和成熟IL-1 β的水平以及半胱天冬酶-1的活性来研究Schs对痤疮丙酸杆菌诱导的NLRP 3炎性小体活化的影响。我们的结果表明，Sch A，B和C抑制痤疮丙酸杆菌诱导的焦亡。此外，三种木脂素显著抑制NLRP 3炎性体活化，具有以下效力：Sch C > Sch B > Sch A。三种木脂素还抑制线粒体ROS的产生和ATP的释放。此外，Sch B和C几乎完全阻止了K+的外排，而Sch A的作用相对较弱。总的来说，我们的新发现表明，在痤疮丙酸杆菌感染的THP-1细胞中，SchA、B和C通过抑制NLRP 3炎性小体活化而有效抑制IL-1 β分泌和细胞凋亡。因此，Schs可能是治疗痤疮丙酸杆菌相关感染的有希望的药物。
Propionibacterium acnes, a common pathogen associated with acne, is also responsible for various surgical infections. Schisandrin A, schisandrin B and schisandrin C, the representative lignans of Schisandra chinensis (Turcz.) Baill. extract, inhibit P. acnes-induced inflammation. However, their effects on P. acnes-induced IL-1 beta secretion and pyroptosis mediated by NLRP3 inflammasome activation remain unknown. In this study, we compared the effects of schisandrin A, B, and C (Sch A, B, and C) on IL-1 beta secretion and pyroptosis in P. acnes-infected THP-1 cells. As NLRP3 plays important roles in P. acnes-mediated inflammation and pyroptosis, we also investigated the effects of Schs on P. acnes-induced NLRP3 inflammasome activation by measuring the levels of NLRP3, active caspase-1, and mature IL-1 beta, and activity of caspase-1. Our results showed that Sch A, B, and C suppressed P. acnes-induced pyroptosis. Further, the three lignans significantly suppressed NLRP3 inflammasome activation, with the following potency: Sch C > Sch B > Sch A. Three lignans also inhibited the production of mitochondrial ROS and ATP release. Additionally, Sch B and C almost completely prevented the efflux of K+, whereas Sch A had a relatively weak effect. Collectively, our novel findings showed that Sch A, B, and C effectively suppressed IL-1 beta secretion and pyroptosis by inhibiting NLRP3 inflammasome activation in P. acnes-infected THP-1 cells. Thus, Schs may be promising agents for the treatment of P. acnes-related infections.