Inhibition of AIM2 inflammasome-mediated pyroptosis by Andrographolide contributes to amelioration of radiation-induced lung inflammation and fibrosis

被引:170
作者
Gao, Jian [1 ]
Peng, Shuang [1 ]
Shan, Xinni [1 ]
Deng, Guoliang [1 ]
Shen, Lihong [1 ]
Sun, Jian [2 ]
Jiang, Chunhong [3 ]
Yang, Xiaoling [3 ]
Chang, Zhigang [4 ]
Sun, Xinchen [4 ]
Feng, Fude [2 ]
Kong, Lingdong [1 ]
Gu, Yanhong [4 ]
Guo, Wenjie [1 ]
Xu, Qiang [1 ,5 ]
Sun, Yang [1 ,5 ,6 ]
机构
[1] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Dept Biotechnol & Pharmaceut Sci, 163 Xianlin Ave, Nanjing 210023, Peoples R China
[2] Nanjing Univ, Sch Chem & Chem Engn, Dept Polymer Sci & Engn, Minist Educ,Key Lab High Performance Polymer Mat, Nanjing 210023, Peoples R China
[3] Jiangxi Qingfeng Pharmaceut Co Ltd, State Key Lab Innovat Nat Med & TCM Inject, Ganzhou, Peoples R China
[4] Nanjing Med Univ, Affiliated Hosp 1, Nanjing 210029, Peoples R China
[5] Xuzhou Med Univ, Jiangsu Key Lab New Drug Res & Clin Pharm, 209 Tongshan Rd, Xuzhou 221004, Jiangsu, Peoples R China
[6] Nanjing Univ, Chem & Biomed Innovat Ctr ChemBIC, Nanjing 210023, Peoples R China
基金
中国国家自然科学基金;
关键词
FACTOR-KAPPA-B; INDUCED ACTIVATION; COLORECTAL-CANCER; SERUM BIOMARKER; CELL-DEATH; RADIOTHERAPY; PNEUMONITIS; MECHANISMS; MICE; INTERLEUKIN-1-BETA;
D O I
10.1038/s41419-019-2195-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:15
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