PMID- 31862870 OWN - NLM STAT- MEDLINE DCOM- 20200911 LR - 20210110 IS - 2041-4889 (Electronic) VI - 10 IP - 12 DP - 2019 Dec 20 TI - Inhibition of AIM2 inflammasome-mediated pyroptosis by Andrographolide contributes to amelioration of radiation-induced lung inflammation and fibrosis. PG - 957 LID - 10.1038/s41419-019-2195-8 [doi] LID - 957 AB - 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. FAU - Gao, Jian AU - Gao J AD - State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. FAU - Peng, Shuang AU - Peng S AD - State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. FAU - Shan, Xinni AU - Shan X AD - State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. FAU - Deng, Guoliang AU - Deng G AD - State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. FAU - Shen, Lihong AU - Shen L AD - State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. FAU - Sun, Jian AU - Sun J AD - Key Laboratory of High Performance Polymer Materials and Technology of Ministry of Education, Department of Polymer Science & Engineering, School of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023, China. FAU - Jiang, Chunhong AU - Jiang C AD - State Key Laboratory of Innovative Nature Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd, Ganzhou, China. FAU - Yang, Xiaoling AU - Yang X AD - State Key Laboratory of Innovative Nature Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd, Ganzhou, China. FAU - Chang, Zhigang AU - Chang Z AD - The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. FAU - Sun, Xinchen AU - Sun X AD - The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. FAU - Feng, Fude AU - Feng F AD - Key Laboratory of High Performance Polymer Materials and Technology of Ministry of Education, Department of Polymer Science & Engineering, School of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023, China. FAU - Kong, Lingdong AU - Kong L AD - State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. FAU - Gu, Yanhong AU - Gu Y AD - The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. FAU - Guo, Wenjie AU - Guo W AUID- ORCID: 0000-0001-8506-3905 AD - State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. FAU - Xu, Qiang AU - Xu Q AD - State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China. FAU - Sun, Yang AU - Sun Y AUID- ORCID: 0000-0003-1425-0089 AD - State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. yangsun@nju.edu.cn. AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China. yangsun@nju.edu.cn. AD - Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, 210023, China. yangsun@nju.edu.cn. LA - eng GR - 81673436/National Natural Science Foundation of China (National Science Foundation of China)/International GR - 91853109/National Natural Science Foundation of China (National Science Foundation of China)/International GR - 81872877/National Natural Science Foundation of China (National Science Foundation of China)/International GR - 81730100/National Natural Science Foundation of China (National Science Foundation of China)/International GR - 2018K100B/Jiangsu Postdoctoral Research Foundation (Jiangsu Province Postdoctoral Research Foundation)/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191220 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Aim2 protein, mouse) RN - 0 (DNA-Binding Proteins) RN - 0 (Diterpenes) RN - 0 (Inflammasomes) RN - 0 (Radiation-Protective Agents) RN - 410105JHGR (andrographolide) SB - IM MH - Abnormalities, Radiation-Induced/*drug therapy/genetics/pathology MH - Animals MH - DNA-Binding Proteins/*genetics MH - Disease Models, Animal MH - Diterpenes/*pharmacology MH - Humans MH - Inflammasomes/drug effects/genetics MH - Inflammation/drug therapy/etiology/genetics/pathology MH - Lung/abnormalities/drug effects/radiation effects MH - Lung Injury/*drug therapy/etiology/pathology MH - Mice MH - Pyroptosis/drug effects/genetics MH - Radiation-Protective Agents/pharmacology PMC - PMC6925222 COIS- The authors declare that they have no conflict of interest. EDAT- 2019/12/22 06:00 MHDA- 2020/09/12 06:00 PMCR- 2019/12/20 CRDT- 2019/12/22 06:00 PHST- 2019/05/09 00:00 [received] PHST- 2019/12/09 00:00 [accepted] PHST- 2019/12/07 00:00 [revised] PHST- 2019/12/22 06:00 [entrez] PHST- 2019/12/22 06:00 [pubmed] PHST- 2020/09/12 06:00 [medline] PHST- 2019/12/20 00:00 [pmc-release] AID - 10.1038/s41419-019-2195-8 [pii] AID - 2195 [pii] AID - 10.1038/s41419-019-2195-8 [doi] PST - epublish SO - Cell Death Dis. 2019 Dec 20;10(12):957. doi: 10.1038/s41419-019-2195-8.