PMID- 22318546
OWN - NLM
STAT- MEDLINE
DCOM- 20120813
LR  - 20211021
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Linking)
VI  - 39
IP  - 6
DP  - 2012 Jun
TI  - PDTC attenuate LPS-induced kidney injury in systemic lupus erythematosus-prone 
      MRL/lpr mice.
PG  - 6763-71
LID - 10.1007/s11033-012-1501-7 [doi]
AB  - Lipopolysaccharide (LPS) from bacteria can accelerate and exacerbate lupus 
      nephritis (LN) and induce infiltrating inflammatory cells in kidney in animal 
      models. Pyrrolidine dithiocarbamate (PDTC) is known to exert anti-inflammatory 
      effects. Monocyte chemoattractant protein-1(MCP-1) is upregulated by various 
      stimuli, including LPS, high glucose, and hyperosmolality. However, the molecular 
      mechanisms of transcriptional regulation of the MCP-1 protein expression with LPS 
      are poorly understood. Expression of MCP-1 was examined by western blot and 
      enzyme-linked immunosorbent assay, respectively. The activity of nuclear factor 
      (NF)-kappaB was measured by western blot. These mice have uncontrolled 
      proliferation of T cells, an impaired response to T cell mitogen and produce 
      autoantibodies against nuclear antigens, including DNA. We found that after LPS 
      treatment for 14 weeks, LPS increased MCP-1 protein expression in kidney, which 
      was significantly suppressed by antioxidant PDTC. The expression of NF-kappaB, pERK, 
      pJNK and MCP-1 were increased, pp38 expression was decreased significantly, 
      concomitantly with sera anti-dsDNA, MCP-1 and the acceleration of severity of 
      autoimmune kidney injury. LPS induce markedly neutrophil infiltration in the 
      glomerulus, especially around the mesangial region. PDTC reduced the number of 
      infiltrating inflammatory cells and severity of kidney injury via inhibiting 
      NF-kappaB and p38 MAPK activity. They also markedly prevented LPS-induced pJNK and 
      MCP-1. Therefore, MCP-1 may be responsible for the recruitment and activation of 
      leukocytes in diseased kidneys in female MRL/lpr mice. In this study, the 
      long-term administration of PDTC had impacts on the prevention of end-stage organ 
      damage induced by LPS treated. We demonstrated that PDTC inhibited LPS-induced 
      monocyte migration and attenuated LPS-induced p38 MAPK activation. Based on these 
      data we infer that PDTC inhibits LPS-induced MCP-1 expression, secretion and 
      function through inhibition of NF-kappaB and p38 MAPK activity. Our study suggests 
      that MAPK is an important therapeutic target of monocyte recruitment and 
      accumulation within the glomerulus in inflammatory renal disease. These results 
      suggest that PDTC protects against kidney inflammation of SLE at least in part 
      via NF-kappaB and MAPK signaling pathways induction, and that inhibitory action on 
      anti-dsDNA may be associated with the protective mechanism of PDTC. In summary, 
      PDTC pretreatment attenuates LPS-induced kidney injury in female MRL/lpr mice 
      through regulating NF-kappaB and MAPK signaling pathways. Our results indicate that 
      LPS induces MCP-1 mainly through activating NF-kappaB and its downstream MAPK, and 
      that such effect was inhibited by PDTC, suggesting the efficacy of PDTC in 
      preventing kidney fibrosis in lupus-prone mice. Therefore, appropriate inhibition 
      of NF-kappaB activation may attenuate the kidney injury in lupus-prone mice.
FAU - Zhai, Jin-Xia
AU  - Zhai JX
AD  - Department of Occupational and Environmental Health, Anhui Medical University, 
      Hefei, Anhui Province, China.
FAU - Zhang, Zhao-Xiang
AU  - Zhang ZX
FAU - Feng, Ya-Juan
AU  - Feng YJ
FAU - Ding, Shu-Shu
AU  - Ding SS
FAU - Wang, Xing-Hua
AU  - Wang XH
FAU - Zou, Li-Wei
AU  - Zou LW
FAU - Ye, Dong-Qing
AU  - Ye DQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120209
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Antioxidants)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Pyrrolidines)
RN  - 0 (Rela protein, mouse)
RN  - 0 (Thiocarbamates)
RN  - 0 (Transcription Factor RelA)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antibodies, Antinuclear/blood
MH  - Antioxidants/*pharmacology/therapeutic use
MH  - Chemokine CCL2/blood/genetics
MH  - Female
MH  - Gene Expression
MH  - Gene Expression Regulation/drug effects
MH  - Glomerulonephritis, Membranoproliferative/etiology/immunology/pathology
MH  - Kidney/pathology
MH  - Lipopolysaccharides/*pharmacology
MH  - Lupus Erythematosus, Systemic/blood/complications/*immunology
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Mice, Inbred MRL lpr
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Phosphorylation
MH  - Proteinuria/prevention & control
MH  - Pyrrolidines/*pharmacology/therapeutic use
MH  - Renal Insufficiency/blood/immunology/*prevention & control
MH  - Thiocarbamates/*pharmacology/therapeutic use
MH  - Transcription Factor RelA/genetics/metabolism
EDAT- 2012/02/10 06:00
MHDA- 2012/08/14 06:00
CRDT- 2012/02/10 06:00
PHST- 2011/08/18 00:00 [received]
PHST- 2012/01/24 00:00 [accepted]
PHST- 2012/02/10 06:00 [entrez]
PHST- 2012/02/10 06:00 [pubmed]
PHST- 2012/08/14 06:00 [medline]
AID - 10.1007/s11033-012-1501-7 [doi]
PST - ppublish
SO  - Mol Biol Rep. 2012 Jun;39(6):6763-71. doi: 10.1007/s11033-012-1501-7. Epub 2012 
      Feb 9.