PMID- 25909495
OWN - NLM
STAT- MEDLINE
DCOM- 20150811
LR  - 20220408
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 66
IP  - 2
DP  - 2015 Aug
TI  - Soluble monosodium urate, but not its crystal, induces toll like receptor 
      4-dependent immune activation in renal mesangial cells.
PG  - 310-8
LID - S0161-5890(15)00354-5 [pii]
LID - 10.1016/j.molimm.2015.03.250 [doi]
AB  - BACKGROUND: Uric acid has emerged as a novel and potential modifiable risk factor 
      for the incidence and progression of kidney diseases, however, the deteriorate 
      effect of uric acid on renal mesangial cells remains unclear. The present study 
      is to examine the immune activation of soluble and crystal forms of uric acid in 
      human mesangial cells. METHODS: We stimulated primary human mesangial cells 
      (HMCs) with increasing concentrations (from 50 to 200 mug/ml) of soluble 
      monosodium urate (MSU) or MSU crystals. We examined interleukin (IL)-1beta protein 
      expression levels in cell culture by ELISA. The stimulated HMCs were further 
      stimulated with soluble MSU or MSU crystals at 200 mug/ml with or without the 
      pre-incubation of toll like receptor (TLR) 4 inhibitor TAK242 (1muM). TLR4, 
      nod-like receptor protein (NLRP3, also known as NALP3), IL-1beta, human leukocyte 
      antigen (HLA)-DR and CD40 were examined by Realtime-PCR, Western blot and ELISA, 
      respectively. RESULTS: We found that both soluble MSU and MSU crystals increased 
      IL-1beta protein expression levels in dose-dependent fashion. Soluble MSU 
      significantly enhanced the expression of TLR4, NLRP3, IL-1beta, HLA-DR and CD40 
      while MSU crystals only upregulated the expression of TLR4 and IL-1beta. TLR4 
      inhibitor TAK242 significantly blocked the up-regulation of NLRP3, IL-1beta, HLA-DR 
      and CD40 induced by soluble MSU while no TAK242 suppression effect on MSU 
      crystals induced IL-1beta up-regulation was found. CONCLUSIONS: Our results 
      suggested that soluble MSU, but not MSU crystals, induce NLRP3, IL-1beta, HLA-DR and 
      CD40 upregulation in a TLR4-dependent manner. These findings indicate that 
      soluble MSU may play a pathological role in hyperuricemia induced renal mesangial 
      injury.
CI  - Copyright (c) 2015. Published by Elsevier Ltd.
FAU - Xiao, Jing
AU  - Xiao J
AD  - Department of Nephrology, Huadong Hospital affiliated to Fudan University, 
      Shanghai, PR China.
FAU - Fu, Chensheng
AU  - Fu C
AD  - Department of Nephrology, Huadong Hospital affiliated to Fudan University, 
      Shanghai, PR China.
FAU - Zhang, Xiaoli
AU  - Zhang X
AD  - Department of Nephrology, Huadong Hospital affiliated to Fudan University, 
      Shanghai, PR China.
FAU - Zhu, Dingyu
AU  - Zhu D
AD  - Department of Nephrology, Huadong Hospital affiliated to Fudan University, 
      Shanghai, PR China.
FAU - Chen, Weijun
AU  - Chen W
AD  - Department of Nephrology, Huadong Hospital affiliated to Fudan University, 
      Shanghai, PR China.
FAU - Lu, Yijun
AU  - Lu Y
AD  - Department of Nephrology, Huadong Hospital affiliated to Fudan University, 
      Shanghai, PR China.
FAU - Ye, Zhibin
AU  - Ye Z
AD  - Department of Nephrology, Huadong Hospital affiliated to Fudan University, 
      Shanghai, PR China. Electronic address: yezb2013@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150421
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (CD40 Antigens)
RN  - 0 (Carrier Proteins)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (Sulfonamides)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate)
RN  - 268B43MJ25 (Uric Acid)
SB  - IM
MH  - CD40 Antigens/*agonists/genetics/immunology
MH  - Carrier Proteins/*agonists/genetics/immunology
MH  - Crystallization
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation
MH  - HLA-DR Antigens/genetics/immunology
MH  - Humans
MH  - Interleukin-1beta/*agonists/genetics/immunology
MH  - Mesangial Cells/cytology/*drug effects/immunology
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Primary Cell Culture
MH  - Signal Transduction
MH  - Solubility
MH  - Sulfonamides/pharmacology
MH  - Toll-Like Receptor 4/*agonists/antagonists & inhibitors/genetics/immunology
MH  - Uric Acid/chemistry/*pharmacology
OTO - NOTNLM
OT  - Human renal mesangial cells
OT  - Immune activation
OT  - Monosodium urate crystal
OT  - Soluble monosodium urate
OT  - Toll like receptor 4
EDAT- 2015/04/25 06:00
MHDA- 2015/08/12 06:00
CRDT- 2015/04/25 06:00
PHST- 2014/05/25 00:00 [received]
PHST- 2015/03/21 00:00 [revised]
PHST- 2015/03/30 00:00 [accepted]
PHST- 2015/04/25 06:00 [entrez]
PHST- 2015/04/25 06:00 [pubmed]
PHST- 2015/08/12 06:00 [medline]
AID - S0161-5890(15)00354-5 [pii]
AID - 10.1016/j.molimm.2015.03.250 [doi]
PST - ppublish
SO  - Mol Immunol. 2015 Aug;66(2):310-8. doi: 10.1016/j.molimm.2015.03.250. Epub 2015 
      Apr 21.