PMID- 32060137
OWN - NLM
STAT- MEDLINE
DCOM- 20201102
LR  - 20201102
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 204
IP  - 6
DP  - 2020 Mar 15
TI  - Tris DBA Ameliorates Accelerated and Severe Lupus Nephritis in Mice by Activating 
      Regulatory T Cells and Autophagy and Inhibiting the NLRP3 Inflammasome.
PG  - 1448-1461
LID - 10.4049/jimmunol.1801610 [doi]
AB  - Tris (dibenzylideneacetone) dipalladium (Tris DBA), a small-molecule palladium 
      complex, has been shown to inhibit cell growth and proliferation in pancreatic 
      cancer, lymphocytic leukemia, and multiple myeloma. In the current study, we 
      examined the therapeutic effects of Tris DBA on glomerular cell proliferation, 
      renal inflammation, and immune cells. Treatment of accelerated and severe lupus 
      nephritis (ASLN) mice with Tris DBA resulted in improved renal function, 
      albuminuria, and pathology, including measurements of glomerular cell 
      proliferation, cellular crescents, neutrophils, fibrinoid necrosis, and 
      tubulointerstitial inflammation in the kidneys as well as scoring for 
      glomerulonephritis activity. The treated ASLN mice also showed significantly 
      decreased glomerular IgG, IgM, and C3 deposits. Furthermore, the compound was 
      able to 1) inhibit bone marrow-derived dendritic cell-mediated T cell functions 
      and reduce serum anti-dsDNA autoantibody levels; 2) differentially regulate 
      autophagy and both the priming and activation signals of the NLRP3 inflammasome; 
      and 3) suppress the phosphorylation of JNK, ERK, and p38 MAPK signaling pathways. 
      Tris DBA improved ASLN in mice through immunoregulation by blunting the MAPK 
      (ERK, JNK)-mediated priming signal of the NLRP3 inflammasome and by regulating 
      the autophagy/NLRP3 inflammasome axis. These results suggest that the pure 
      compound may be a drug candidate for treating the accelerated and deteriorated 
      type of lupus nephritis.
CI  - Copyright (c) 2020 by The American Association of Immunologists, Inc.
FAU - Wu, Chung-Yao
AU  - Wu CY
AD  - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 
      Taiwan 114.
FAU - Hua, Kuo-Feng
AU  - Hua KF
AD  - Department of Biotechnology and Animal Science, National Ilan University, Yilan, 
      Taiwan 260.
FAU - Chu, Ching-Liang
AU  - Chu CL
AD  - Graduate Institute of Immunology, National Taiwan University College of Medicine, 
      Taipei, Taiwan 106; shukmanka@gmail.com annchen31717@gmail.com.
FAU - Yang, Shin-Ruen
AU  - Yang SR
AD  - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 
      Taiwan 114.
FAU - Arbiser, Jack L
AU  - Arbiser JL
AD  - Department of Dermatology, Emory School of Medicine, Atlanta, GA 30322.
AD  - Winship Cancer Institute, Emory School of Medicine, Atlanta, GA 30322.
AD  - Atlanta Veterans Administration Medical Center, Decatur, GA 30033.
FAU - Yang, Sung-Sen
AU  - Yang SS
AD  - Division of Nephrology, Department of Internal Medicine, Tri-Service General 
      Hospital, National Defense Medical Center, Taipei, Taiwan 114; 
      shukmanka@gmail.com annchen31717@gmail.com.
FAU - Lin, Yu-Chuan
AU  - Lin YC
AD  - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 
      Taiwan 114.
FAU - Liu, Feng-Cheng
AU  - Liu FC
AD  - Division of Rheumatology/Immunology and Allergy, Department of Medicine, 
      Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 
      114.
FAU - Yang, Shun-Min
AU  - Yang SM
AD  - Institute of Physics, Academia Sinica, Taipei, Taiwan 114.
FAU - Ka, Shuk-Man
AU  - Ka SM
AD  - Graduate Institute of Aerospace and Undersea Medicine, Academy of Medicine, 
      National Defense Medical Center, Taipei, Taiwan 114; and.
FAU - Chen, Ann
AU  - Chen A
AD  - Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 
      Taiwan 114; shukmanka@gmail.com annchen31717@gmail.com.
AD  - Department of Pathology, Tri-Service General Hospital, National Defense Medical 
      Center, Taipei, Taiwan 114.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200214
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Organometallic Compounds)
RN  - 0 (tris(dibenzylideneacetone)dipalladium)
SB  - IM
MH  - Animals
MH  - Autophagy/drug effects
MH  - Cell Communication/drug effects/immunology
MH  - Dendritic Cells/immunology/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Inflammasomes/*antagonists & inhibitors/immunology/metabolism
MH  - Kidney Glomerulus/immunology/metabolism/pathology
MH  - Lupus Nephritis/diagnosis/*drug therapy/immunology/pathology
MH  - Lymphocyte Activation/*drug effects
MH  - MAP Kinase Signaling System/drug effects/immunology
MH  - Mice
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & 
      inhibitors/immunology/metabolism
MH  - Organometallic Compounds/*pharmacology/therapeutic use
MH  - Severity of Illness Index
MH  - T-Lymphocytes, Regulatory/drug effects/*immunology
EDAT- 2020/02/16 06:00
MHDA- 2020/11/03 06:00
CRDT- 2020/02/16 06:00
PHST- 2018/12/10 00:00 [received]
PHST- 2020/01/10 00:00 [accepted]
PHST- 2020/02/16 06:00 [pubmed]
PHST- 2020/11/03 06:00 [medline]
PHST- 2020/02/16 06:00 [entrez]
AID - jimmunol.1801610 [pii]
AID - 10.4049/jimmunol.1801610 [doi]
PST - ppublish
SO  - J Immunol. 2020 Mar 15;204(6):1448-1461. doi: 10.4049/jimmunol.1801610. Epub 2020 
      Feb 14.