Micheliolide Attenuates Lipopolysaccharide-Induced Inflammation by Modulating the mROS/NF-κB/NLRP3 Axis in Renal Tubular Epithelial Cells
Micheliolide Attenuates Lipopolysaccharide-Induced Inflammation by Modulating the mROS/NF-κB/NLRP3 Axis in Renal Tubular Epithelial Cells
复制标题
Micheliolide 通过调节肾小管上皮细胞中的 mROS/NF-κB/NLRP3 轴来减轻脂多糖诱导的炎症
DOI：
10.1155/2020/3934769
复制
发表时间：
2020-08-17
影响因子：
4.6
通讯作者：
Long, Haibo
中科院分区：
文献类型：
--
作者：
Lei, Xianghong;Li, Shuting;Long, Haibo
慢性肾脏病是一种与肾小管炎症和氧化应激密切相关的常见疾病，目前尚无有效的治疗方法。核苷酸结合寡聚化结构域样受体蛋白3（NLRP 3）炎性体的激活是肾脏炎症的重要因素，但其机制尚不清楚。含笑属植物是一种具有抗氧化和抗炎作用的新化合物，在肿瘤和炎症性疾病中具有多种作用。本研究探讨了MCL对脂多糖（LPS）诱导的肾小管细胞炎症反应的影响及其机制。我们发现MCL显著抑制LPS诱导的NF-κB信号传导和细胞因子如肿瘤坏死因子-α和单核细胞趋化蛋白-1在大鼠近端肾小管细胞系（NRK-52 E）中的炎症表达。MCL还在体外阻止LPS和三磷酸腺苷诱导的NLRP 3炎性体活化，如通过抑制NLRP 3表达、半胱天冬酶-1切割以及白细胞介素-1 β和白细胞介素-18成熟和分泌所证明的。此外，MCL抑制线粒体膜电位的降低，减少活性氧（ROS）的释放。此外，MCL可以阻止鱼藤酮（一种众所周知的线粒体活性氧（mROS）激动剂）诱导的NLRP 3炎性小体激活，表明MCL的抗炎作用机制可能与mROS密切相关。结论：MCL可通过抑制肾小管上皮细胞mROS/NF-κB/NLRP 3轴来抑制LPS诱导的肾脏炎症反应。
Chronic kidney disease is a common disease closely related to renal tubular inflammation and oxidative stress, and no effective treatment is available. Activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important factor in renal inflammation, but the mechanism remains unclear. Micheliolide (MCL), which is derived from parthenolide, is a new compound with antioxidative and anti-inflammatory effects and has multiple roles in tumors and inflammatory diseases. In this study, we investigated the effect of MCL on lipopolysaccharide- (LPS-) induced inflammation in renal tubular cells and the related mechanism. We found that MCL significantly suppressed the LPS-induced NF-κB signaling and inflammatory expression of cytokines, such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in a rat renal proximal tubular cell line (NRK-52E). MCL also prevented LPS- and adenosine triphosphate-induced NLRP3 inflammasome activation in vitro, as evidenced by the inhibition of NLRP3 expression, caspase-1 cleavage, and interleukin-1β and interleukin-18 maturation and secretion. Additionally, MCL inhibited the reduction of mitochondrial membrane potential and decreases the release of reactive oxygen species (ROS). Moreover, MCL can prevent NLRP3 inflammasome activation induced by rotenone, a well-known mitochondrial ROS (mROS) agonist, indicating that the mechanism of MCL's anti-inflammatory effect may be closely related to the mROS. In conclusion, our study indicates that MCL can inhibit LPS-induced renal inflammation through suppressing the mROS/NF-κB/NLRP3 axis in tubular epithelial cells.