PMID- 26364141
OWN - NLM
STAT- MEDLINE
DCOM- 20160126
LR  - 20220410
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 68
IP  - 2 Pt A
DP  - 2015 Dec
TI  - Effects of ROS-relative NF-kappaB signaling on high glucose-induced TLR4 and MCP-1 
      expression in podocyte injury.
PG  - 261-71
LID - S0161-5890(15)30066-3 [pii]
LID - 10.1016/j.molimm.2015.09.002 [doi]
AB  - High glucose (HG) induced inflammation is central to progression in diabetic 
      nephropathy (DN). Recent studies have suggested that nuclear factor-kappa B 
      (NF-kappaB) signaling activation is associated with DN, and podocyte damage may be 
      involved in orchestrating these effects. Therefore, the aim of this study was to 
      investigate the effects of NF-kappaB signaling on podocytes under HG conditions. The 
      effects of HG and NF-kappaB signaling on podocytes were assessed by CCK-8 assay, 
      cellular NF-kappaB translocation assay, measurement of reactive oxygen species (ROS) 
      and Western blot analysis. We found that HG reduced cell viability, activated 
      NF-kappaB signaling and up-regulated toll-like receptor 4 (TLR4) and monocyte 
      chemoattractant protein-1 (MCP-1). In these cells, NF-kappaB inhibition with ammonium 
      pyrrolidinethiocarbamate (PDTC) resulted in effectively constraining TLR4 and 
      MCP-1 up-regulation, indicating that protective effects associated with the 
      inhibition of NF-kappaB were linked to TLR4 and MCP-1 down-regulation in podocytes. 
      Furthermore, HG significantly increased the production of intracellular ROS. 
      Pretreatment with N-acetyl-l-cysteine (NAC) significantly inhibited intracellular 
      ROS generation and increased cell viability, accompanied by a significant NF-kappaB 
      inhibition and suppression of TLR4 and inflammatory cytokine MCP-1 expression. 
      Collectively, our novel data suggest that HG induces the over-experssion of TLR-4 
      and MCP-1 through a NF-kappaB-dependent signaling. NF-kappaB-mediated increased 
      inflammation is possibly via ROS and contributes to the cell injury. These 
      results may provide potential therapeutic target for diabetic nephropathy in the 
      future.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Wei, Miaomiao
AU  - Wei M
AD  - College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin 
      Key Laboratory of Tumor Microenvironment and Neuro-vascular Regulation, Nankai 
      University, Tianjin 300071, China.
FAU - Li, Zhigui
AU  - Li Z
AD  - College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin 
      Key Laboratory of Tumor Microenvironment and Neuro-vascular Regulation, Nankai 
      University, Tianjin 300071, China.
FAU - Xiao, Lu
AU  - Xiao L
AD  - College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin 
      Key Laboratory of Tumor Microenvironment and Neuro-vascular Regulation, Nankai 
      University, Tianjin 300071, China.
FAU - Yang, Zhuo
AU  - Yang Z
AD  - College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin 
      Key Laboratory of Tumor Microenvironment and Neuro-vascular Regulation, Nankai 
      University, Tianjin 300071, China. Electronic address: zhuoyang@nankai.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150909
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyrrolidines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Thiocarbamates)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - IY9XDZ35W2 (Glucose)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Cell Line, Transformed
MH  - Chemokine CCL2/genetics/*immunology
MH  - Gene Expression Regulation
MH  - Glucose/*toxicity
MH  - Inflammation
MH  - Mice
MH  - NF-kappa B/antagonists & inhibitors/genetics/*immunology
MH  - Podocytes/*drug effects/immunology/pathology
MH  - Pyrrolidines/pharmacology
MH  - Reactive Oxygen Species/agonists/antagonists & inhibitors/*metabolism
MH  - Signal Transduction
MH  - Thiocarbamates/pharmacology
MH  - Toll-Like Receptor 4/genetics/*immunology
OTO - NOTNLM
OT  - Monocyte chemoattractant protein-1
OT  - Nuclear factor-kappa B
OT  - Podocytes
OT  - Toll-like receptor-4
EDAT- 2015/09/14 06:00
MHDA- 2016/01/27 06:00
CRDT- 2015/09/14 06:00
PHST- 2015/07/26 00:00 [received]
PHST- 2015/08/31 00:00 [revised]
PHST- 2015/09/01 00:00 [accepted]
PHST- 2015/09/14 06:00 [entrez]
PHST- 2015/09/14 06:00 [pubmed]
PHST- 2016/01/27 06:00 [medline]
AID - S0161-5890(15)30066-3 [pii]
AID - 10.1016/j.molimm.2015.09.002 [doi]
PST - ppublish
SO  - Mol Immunol. 2015 Dec;68(2 Pt A):261-71. doi: 10.1016/j.molimm.2015.09.002. Epub 
      2015 Sep 9.