Inhibition of AIM2 inflammasome-mediated pyroptosis by Andrographolide contributes to amelioration of radiation-induced lung inflammation and fibrosis
Inhibition of AIM2 inflammasome-mediated pyroptosis by Andrographolide contributes to amelioration of radiation-induced lung inflammation and fibrosis
复制标题
穿心莲内酯抑制 AIM2 炎症小体介导的细胞焦亡有助于改善辐射引起的肺部炎症和纤维化
DOI：
10.1038/s41419-019-2195-8
复制
发表时间：
2019-12-20
影响因子：
9
通讯作者：
Sun, Yang
中科院分区：
文献类型：
--
作者：
Gao, Jian;Peng, Shuang;Sun, Yang
放射性肺损伤（RILI）是胸部放射治疗最常见和致命的并发症之一，而没有有效的干预措施。穿心莲是从穿心莲中提取的活性成分，用于治疗上呼吸道感染。本文报道穿心莲内酯对RILI的辐射防护作用及其机制。C57 BL/6小鼠接受18戈伊的全胸照射，然后每隔一天腹腔注射穿心莲，持续4周。穿心莲内酯显著改善放射性肺组织损伤、炎性细胞浸润和早期促炎细胞因子释放以及晚期进行性纤维化。此外，穿心莲内酯显着阻碍辐射诱导的AIM2炎性小体的激活和体内细胞凋亡。此外，骨髓源性巨噬细胞（BMDM）在体外暴露于8戈伊的X射线辐射，穿心莲显着抑制AIM 2炎性小体介导的BMDM细胞的热凋亡。从机制上讲，穿心莲有效地阻止AIM 2易位到细胞核中，以感知BMDM中放射或化疗剂诱导的DNA损伤。综上所述，穿心莲内酯通过抑制巨噬细胞中AIM2炎性小体介导的焦亡来改善RILI，将穿心莲内酯鉴定为RILI的新型潜在保护剂。
Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy, whereas no effective interventions are available. Andrographolide, an active component extracted from Andrographis paniculate, is prescribed as a treatment for upper respiratory tract infection. Here we report the potential radioprotective effect and mechanism of Andrographolide on RILI. C57BL/6 mice were exposed to 18 Gy of whole thorax irradiation, followed by intraperitoneal injection of Andrographolide every other day for 4 weeks. Andrographolide significantly ameliorated radiation-induced lung tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine release in the early phase and progressive fibrosis in the late phase. Moreover, Andrographolide markedly hampered radiation-induced activation of the AIM2 inflammasome and pyroptosis in vivo. Furthermore, bone marrow-derived macrophages (BMDMs) were exposed to 8 Gy of X-ray radiation in vitro and Andrographolide significantly inhibited AIM2 inflammasome mediated-pyroptosis in BMDMs. Mechanistically, Andrographolide effectively prevented AIM2 from translocating into the nucleus to sense DNA damage induced by radiation or chemotherapeutic agents in BMDMs. Taken together, Andrographolide ameliorates RILI by suppressing AIM2 inflammasome mediated-pyroptosis in macrophage, identifying Andrographolide as a novel potential protective agent for RILI.