PMID- 36585288
OWN - NLM
STAT- MEDLINE
DCOM- 20230223
LR  - 20230223
IS  - 1873-569X (Electronic)
IS  - 0923-1811 (Linking)
VI  - 108
IP  - 3
DP  - 2022 Dec
TI  - Cathepsin B/NLRP3/GSDMD axis-mediated macrophage pyroptosis induces inflammation 
      and fibrosis in systemic sclerosis.
PG  - 127-137
LID - S0923-1811(22)00277-8 [pii]
LID - 10.1016/j.jdermsci.2022.12.006 [doi]
AB  - BACKGROUND: Pyroptosis is a newly discovered type of programmed cell death 
      associated with inflammatory and fibrotic diseases. Macrophages play an important 
      role in inducing early immune inflammation in systemic sclerosis (SSc). 
      OBJECTIVE: To investigate the effect of macrophages pyroptosis on fibrosis of 
      SSc. METHODS: Pyroptosis/inflammatory markers in serum and skin of SSc patients 
      were detected. Bleomycin (BLM) was subcutaneously injected to establish SSc mouse 
      model. The levels of pyroptosis markers, dermal thickness and collagen deposition 
      in skin were assessed before and after the administration of pyroptosis 
      inhibitors, including MCC950, Disulfiram and necrosulfonamide (NSA). 
      Human-derived monocyte-macrophage cell line (THP-1) or mouse bone marrow-derived 
      macrophages (BMDMs) were primed with lipopolysaccharide (LPS) and stimulated by 
      silicon dioxide (SiO(2)) to induce cell pyroptosis. Fibroblasts from patients 
      with SSc were co-cultured with pyroptotic THP-1 cells, and the collagen 
      production was assessed. RESULTS: Pyroptotic/inflammatory proteins, including 
      NLRP3, cleaved-Caspase (CASP)1, GSDMD-N terminal and IL-18 were increased in the 
      serum, and ASC aggregation and GSDMD were elevated in macrophages in the skin of 
      SSc patients. SSc mice showed increased pyroptosis markers, dermal thickness and 
      collagen deposition in skins, which were alleviated by MCC950, Disulfiram and 
      NSA. Pyroptosis of THP-1 cells and BMDMs was induced by LPS/SiO(2), and it was 
      reduced by the inhibitors of Cathepsin B, NLRP3, CASP1 and GSDMD. Co-culture with 
      pyroptotic THP-1 cells increased the fibrotic proteins in fibroblasts, which were 
      alleviated by pyroptosis inhibitors. CONCLUSIONS: SSc patients and BLM-induced 
      mouse model presented increased pyroptosis. LPS/SiO(2)-induced macrophage 
      pyroptosis promoted fibrosis of SSc through Cathepsin B/NLRP3/GSDMD pathway.
CI  - Copyright (c) 2022 Japanese Society for Investigative Dermatology. Published by 
      Elsevier B.V. All rights reserved.
FAU - Liu, Chaofan
AU  - Liu C
AD  - Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Tang, Jiaxuan
AU  - Tang J
AD  - Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Liu, Shiying
AU  - Liu S
AD  - Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Shen, Chen
AU  - Shen C
AD  - Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University 
      School of Medicine, Shanghai, China.
FAU - Zhou, Xing
AU  - Zhou X
AD  - Department of Dermatology, Shanghai Children's Hospital, Shanghai Jiao Tong 
      University, Shanghai, China.
FAU - Lu, Jinghao
AU  - Lu J
AD  - Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Li, Ming
AU  - Li M
AD  - Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Zhu, Lubing
AU  - Zhu L
AD  - Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China. 
      Electronic address: zhu.lubing@zs-hospital.sh.cn.
LA  - eng
PT  - Journal Article
DEP - 20221224
PL  - Netherlands
TA  - J Dermatol Sci
JT  - Journal of dermatological science
JID - 9011485
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - EC 3.4.22.1 (Cathepsin B)
RN  - 0 (Lipopolysaccharides)
RN  - TR3MLJ1UAI (Disulfiram)
RN  - 7631-86-9 (Silicon Dioxide)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - 0 (Inflammasomes)
RN  - 0 (GSDMD protein, human)
RN  - 0 (Nlrp3 protein, mouse)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Pyroptosis
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Cathepsin B/metabolism/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Disulfiram/metabolism/pharmacology
MH  - Silicon Dioxide/metabolism/pharmacology
MH  - Macrophages
MH  - Inflammation/metabolism
MH  - Caspase 1/metabolism
MH  - Disease Models, Animal
MH  - Fibrosis
MH  - *Scleroderma, Systemic/metabolism
MH  - Inflammasomes/metabolism
OTO - NOTNLM
OT  - Collagen
OT  - Macrophage
OT  - Pyroptosis
OT  - Silicon dioxide
OT  - Systemic sclerosis
COIS- Declaration of Competing Interest The authors have no conflict of interest to 
      declare.
EDAT- 2022/12/31 06:00
MHDA- 2023/02/25 06:00
CRDT- 2022/12/30 21:53
PHST- 2022/04/10 00:00 [received]
PHST- 2022/12/01 00:00 [revised]
PHST- 2022/12/20 00:00 [accepted]
PHST- 2022/12/31 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2022/12/30 21:53 [entrez]
AID - S0923-1811(22)00277-8 [pii]
AID - 10.1016/j.jdermsci.2022.12.006 [doi]
PST - ppublish
SO  - J Dermatol Sci. 2022 Dec;108(3):127-137. doi: 10.1016/j.jdermsci.2022.12.006. 
      Epub 2022 Dec 24.