Department of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of Korea.
Department of Food Science and Engineering, Seowon University, Cheongju, Republic of Korea.
Mediators Inflamm. 2018 Mar 4;2018:6054069. doi: 10.1155/2018/6054069. eCollection 2018.
var. (Asteraceae, ) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of extract (APO) on interleukin- (IL-) 1 regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model . The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. evaluation revealed that intraperitoneal administration of APO reduced IL-1 levels, significantly ( < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis.
(菊科)是一种广为人知的传统草药,在韩国、日本、中国和其他亚洲国家被用于治疗各种炎症性疾病。在本研究中,我们研究了 提取物(APO)对骨髓来源的巨噬细胞(BMDM)中白细胞介素-(IL-)1 调节和炎症小体激活的影响,并在尿酸单钠(MSU)诱导的腹膜炎小鼠模型中进行了研究。APO 处理预先用脂多糖(LPS)刺激的 BMDM 可以分别减弱危险信号(如 ATP、 Nigericin、硅晶体和聚(dA:dT))诱导的 NLRP3 和 AIM2 炎症小体激活。机制研究表明,APO 抑制 ASC 寡聚化和斑点形成,这是炎症小体激活所必需的。APO 处理还减少了 LPS 和酪氨酸磷酸酶抑制剂联合作用诱导的 ASC 磷酸化。体内评价显示,APO 腹腔内给药可显著(<0.05)和剂量依赖性地降低 MSU 诱导的腹膜炎小鼠模型中的 IL-1 水平。总之,我们的研究首次报道了 提取物通过调节 ASC 磷酸化抑制炎症小体激活。因此,APO 可能被开发为治疗炎症小体介导的炎症性疾病(如痛风性关节炎)的治疗潜力。