PMID- 33064961
OWN - NLM
STAT- MEDLINE
DCOM- 20210928
LR  - 20210928
IS  - 1208-6002 (Electronic)
IS  - 0829-8211 (Linking)
VI  - 99
IP  - 3
DP  - 2021 Jun
TI  - Blockade of anti-dsDNA ameliorates systemic lupus erythematosus in MRL/Faslpr 
      mice through ameliorating inflammation via the PKCdelta-NLRC4 axis.
PG  - 313-321
LID - 10.1139/bcb-2020-0265 [doi]
AB  - Anti-double-stranded DNA (anti-dsDNA) is closely associated with the inflammatory 
      burden in the brain after ischemic stroke. Here, we studied the inflammatory 
      cascade and investigated the mechanisms behind the pro-inflammatory role of dsDNA 
      in systemic lupus erythematosus (SLE). The serum levels of interleukin-1beta 
      (IL-1beta) and IL-6 in SLE patients and the corresponding controls were evaluated 
      using ELISA, and the expression level of caspase-1 was evaluated using 
      quantitative real-time polymerase chain reaction (qRT-PCR). We found that the 
      serum levels of IL-1beta and IL-6 were increased in the SLE patients. The expression 
      of caspase-1 was upregulated and positively correlated with the levels of 
      pro-inflammatory factors. The level of anti-dsDNA was also elevated and 
      positively correlated with the results for the mean fluorescence intensity (MFI) 
      of caspase-1. Additionally, we evaluated the functions of PRKCD encoding protein 
      kinase c delta (PKCdelta) and NLRC4, in vivo, in MRL/Faslpr mice. We found that renal 
      injury was aggravated, and the levels of pro-inflammatory factors were increased 
      in the MRL/Faslpr mice. We also found that increased levels of NLRC4 in the mice 
      exacerbated renal injury and increased the levels of pro-inflammatory factors, 
      whereas inhibition of PKCdelta had the opposite results. These findings provide 
      unique perspectives on pathogenesis of SLE and indicate that inhibition of 
      anti-dsDNA could attenuate renal inflammatory burden, representing a promising 
      therapeutic opportunity for SLE.
FAU - Yang, Fan
AU  - Yang F
AD  - Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710004, Shaanxi, P.R. China.
AD  - Department of Plastic Surgery and Burns, Taihe Hospital, Hubei University of 
      Medicine, Shiyan 442000, Hubei, P.R. China.
FAU - Yang, Yinhui
AU  - Yang Y
AD  - Department of Plastic Surgery and Burns, Taihe Hospital, Hubei University of 
      Medicine, Shiyan 442000, Hubei, P.R. China.
FAU - Zeng, Weihui
AU  - Zeng W
AD  - Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710004, Shaanxi, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20201016
PL  - Canada
TA  - Biochem Cell Biol
JT  - Biochemistry and cell biology = Biochimie et biologie cellulaire
JID - 8606068
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (CARD Signaling Adaptor Proteins)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (NLRC4 protein, human)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Antibodies, Antinuclear/*chemistry/immunology
MH  - CARD Signaling Adaptor Proteins/genetics/*metabolism
MH  - Calcium-Binding Proteins/genetics/*metabolism
MH  - Case-Control Studies
MH  - DNA/*immunology
MH  - *Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Inflammation/immunology/metabolism/pathology/*prevention & control
MH  - Lupus Erythematosus, Systemic/immunology/metabolism/pathology/*prevention & 
      control
MH  - Male
MH  - Mice
MH  - Mice, Inbred MRL lpr
MH  - Protein Kinase C-delta/genetics/*metabolism
OTO - NOTNLM
OT  - NLRC4 inflammasome
OT  - PKCdelta
OT  - anticorps contre l'ADN double brin
OT  - dommage renal
OT  - double-stranded DNA antibody
OT  - inflammasome NLRC4
OT  - lupus erythemateux dissemine
OT  - renal injury
OT  - systemic lupus erythematosus
EDAT- 2020/10/17 06:00
MHDA- 2021/09/29 06:00
CRDT- 2020/10/16 20:09
PHST- 2020/10/17 06:00 [pubmed]
PHST- 2021/09/29 06:00 [medline]
PHST- 2020/10/16 20:09 [entrez]
AID - 10.1139/bcb-2020-0265 [doi]
PST - ppublish
SO  - Biochem Cell Biol. 2021 Jun;99(3):313-321. doi: 10.1139/bcb-2020-0265. Epub 2020 
      Oct 16.