NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages.
A limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death. We observed an increasing proportion of pyroptosis and elevating Caspase-1 activation in 10 and 20 Gy radiation groups. Nlrp3 knock out significantly diminished the quantity of cleaved-Caspase-1 (p10) and IL-1β as well as the proportion of pyroptosis. Additionally, in vivo research shows that 9.5 Gy of radiation promotes Caspase-1 activation in marginal zone cells and induces death in mice, both of which can be significantly inhibited by knocking out Nlrp3. Thus, based on these findings, we conclude that the NLRP3 inflammasome activation mediates radiation-induced pyroptosis in BMDMs. Targeting NLRP3 inflammasome and pyroptosis may serve as effective strategies to diminish injury caused by radiation.
Department of Health Toxicology, College of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China.
Yan-Gang
YG
Liu
Department of Health Toxicology, College of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China.
Ji-Kuai
JK
Chen
Department of Health Toxicology, College of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China.
Zi-Teng
ZT
Zhang
Department of Health Toxicology, College of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China.
Xiu-Juan
XJ
Ma
Department of Health Toxicology, College of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China.
Yong-Chun
YC
Chen
Department of Health Toxicology, College of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China.
Xiu-Ming
XM
Du
Radiology Department X-ray Room, The Second People's Hospital, Neijiang, Sichuan 641100, China.
Hong
H
Liu
Department of Health Toxicology, College of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China.
Ying
Y
Zong
Department of Health Toxicology, College of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China.|CTI Biotechnology (Suzhou) Co., Ltd, Jiangsu 215300, China.
Guo-Cai
GC
Lu
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D000069292:Pyroptosis / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; D020170:Caspase 1