PMID- 32555186
OWN - NLM
STAT- MEDLINE
DCOM- 20210318
LR  - 20210618
IS  - 2041-4889 (Electronic)
VI  - 11
IP  - 6
DP  - 2020 Jun 18
TI  - Induction of ASC pyroptosis requires gasdermin D or caspase-1/11-dependent 
      mediators and IFNbeta from pyroptotic macrophages.
PG  - 470
LID - 10.1038/s41419-020-2664-0 [doi]
LID - 470
AB  - Mesenchymal stem cells (MSCs) have been used in cell-based therapies for a 
      variety of disorders. Some factors such as inflammatory mediators in the diseased 
      area might damage the survival of MSCs and affect their efficacy. Pyroptosis is a 
      form of programmed necrosis as a response for immune cells to cytosolic 
      pathogenic stimuli. Whether MSCs develop pyroptosis under pathological 
      stimulation, its underlying mechanism and biological significance are still 
      unclear. Here, we found that LPS, flagellin, dsDNA, nigericin (NIG), or LPS 
      combined with nigericin (LPS/NIG) could not induce pyroptosis in 
      adipose-tissue-derived mesenchymal stem cells (ASCs). However, when applied the 
      culture media collected from LPS/NIG-induced pyroptotic bone marrow-derived 
      macrophages (BMDMs) to incubate ASCs, ASCs developed pyroptosis. Inhibition of 
      caspases or deletion of Caspase-1/11 in ASCs did not affect the pyroptotic 
      macrophage media-triggered ASC pyroptosis while ablation of Caspase-1/11 
      abolished BMDM pyroptosis induced by LPS/NIG. Media collected from LPS/NIG 
      stimulated Gsdmd(-/-) or Caspase-1/11(-/-) BMDMs could not induce pyroptosis of 
      ASCs. In addition, RNA-seq analysis showed that interferon (IFN)-stimulated genes 
      were upregulated in pyroptotic ASCs. Adding IFNbeta could boost LPS/NIG stimulated 
      BMDM media-induced ASC pyroptosis. Surprisingly, the pyroptotic ASCs had a lower 
      bactericidal ability to P. Aeruginosa. Taken together, induction of ASC 
      pyroptosis requires gasdermin D or caspase-1/11-dependent mediators and IFNbeta from 
      pyroptotic macrophages.
FAU - Zhang, Cuiping
AU  - Zhang C
AD  - Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, 
      Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
AD  - Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan 
      University, 361015, Xiamen, China.
FAU - Zhao, Caiqi
AU  - Zhao C
AD  - Unit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese 
      Academy of Sciences, 200031, Shanghai, China.
AD  - University of Chinese Academy of Sciences, 100039, Beijing, China.
FAU - Chen, Xiaoyan
AU  - Chen X
AD  - Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, 
      Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
FAU - Tao, Rujia
AU  - Tao R
AD  - Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital, 
      Tongji University, 200433, Shanghai, China.
FAU - Wang, Sijiao
AU  - Wang S
AD  - Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, 
      Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
AD  - Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan 
      University, 361015, Xiamen, China.
FAU - Meng, Guangxun
AU  - Meng G
AD  - The Center for Microbes, Development and Health, Unit of Innate Immunity, 
      Institut Pasteur of Shanghai, Chinese Academy of Sciences, 200031, Shanghai, 
      China.
FAU - Liu, Xing
AU  - Liu X
AD  - The Center for Microbes, Development and Health, Unit of Anti-Infective Immunity 
      and Immune Diseases, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 
      200031, Shanghai, China.
FAU - Shao, Changzhou
AU  - Shao C
AD  - Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, 
      Zhongshan Hospital, Fudan University, 200032, Shanghai, China. 
      sczzhongshan@126.com.
AD  - Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan 
      University, 361015, Xiamen, China. sczzhongshan@126.com.
FAU - Su, Xiao
AU  - Su X
AD  - Unit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese 
      Academy of Sciences, 200031, Shanghai, China. xsu@ips.ac.cn.
AD  - University of Chinese Academy of Sciences, 100039, Beijing, China. xsu@ips.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200618
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Gsdmd protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Phosphate-Binding Proteins)
RN  - 12777-81-0 (Flagellin)
RN  - 77238-31-4 (Interferon-beta)
RN  - 9007-49-2 (DNA)
RN  - EC 3.4.22.- (Casp4 protein, mouse)
RN  - EC 3.4.22.- (Caspases, Initiator)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - RRU6GY95IS (Nigericin)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Caspase 1/*metabolism
MH  - Caspases, Initiator/*metabolism
MH  - DNA/metabolism
MH  - Flagellin/pharmacology
MH  - Interferon-beta/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/drug effects/*metabolism
MH  - Male
MH  - Mesenchymal Stem Cells/*cytology/drug effects/*metabolism
MH  - Mice, Inbred C57BL
MH  - Nigericin/pharmacology
MH  - Phosphate-Binding Proteins/*metabolism
MH  - *Pyroptosis
MH  - Transcriptome/drug effects/genetics
MH  - Up-Regulation/drug effects
PMC - PMC7303158
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/06/20 06:00
MHDA- 2021/03/19 06:00
PMCR- 2020/06/18
CRDT- 2020/06/20 06:00
PHST- 2019/12/07 00:00 [received]
PHST- 2020/05/13 00:00 [accepted]
PHST- 2020/05/10 00:00 [revised]
PHST- 2020/06/20 06:00 [entrez]
PHST- 2020/06/20 06:00 [pubmed]
PHST- 2021/03/19 06:00 [medline]
PHST- 2020/06/18 00:00 [pmc-release]
AID - 10.1038/s41419-020-2664-0 [pii]
AID - 2664 [pii]
AID - 10.1038/s41419-020-2664-0 [doi]
PST - epublish
SO  - Cell Death Dis. 2020 Jun 18;11(6):470. doi: 10.1038/s41419-020-2664-0.