PMID- 12399623
OWN - NLM
STAT- MEDLINE
DCOM- 20030717
LR  - 20171101
IS  - 1660-8151 (Print)
IS  - 1660-8151 (Linking)
VI  - 92
IP  - 4
DP  - 2002 Dec
TI  - Differential expression of MCP-1 and its receptor CCR2 in glucose primed human 
      mesangial cells.
PG  - 797-806
AB  - BACKGROUND: Glomerular mononuclear cell infiltration is associated with the 
      development of a diffuse glomerulosclerosis in patients with diabetic 
      nephropathy. Monocyte chemoattractant protein-1 (MCP-1) plays an important role 
      in the recruitment and accumulation of monocytes and lymphocytes within the 
      glomerulus. In the present study, we examined whether the ambient glucose 
      concentration alters the expression of MCP-1 and its receptor CCR2 in primary 
      human mesangial cells (HMC). METHODS: MCP-1 mRNA expression was assessed by 
      Northern blot and CCR2 mRNA expression by RT-PCR analysis. MCP-1 protein 
      production was determined by ELISA. Migration studies were performed to assess 
      functional MCP-1 receptor expression. RESULTS: Exposure of HMC to 30 mM D-glucose 
      led to a 30% increase in MCP-1 mRNA expression as compared to 5 mM D-glucose and 
      osmotic controls while there was no difference in MCP-1 protein production. 
      Simultaneously, CCR2 mRNA expression was down-regulated in HMC exposed to 30 mM 
      D-glucose. 5 mM D-glucose primed HMC showed a dose-dependent migration towards 
      MCP-1 that was dose-dependently inhibited by pertussis toxin, the broad-spectrum 
      chemokine antagonist vMIP-II as well as the CCR2 receptor antagonist 
      (1-8del)MCP-1--demonstrating functional activity of MCP-1 receptor expression in 
      primary HMC. In accordance with the downregulatory effects of 30 mM D-glucose on 
      CCR2 mRNA expression no migratory response towards MCP-1 was observed under these 
      conditions. The additional proinflammatory stimulus TNFalpha increased MCP-1 
      protein production in 30 as compared to 5 mM D-glucose primed HMC (2,194 +/- 568 
      vs. 1,422 +/- 379 pg MCP-1/10(4) cells x ml in 30 vs. 5 mM D-glucose primed HMC 
      +24 h TNFalpha 500 U/ml, p = 0.002). However, this was not associated with an 
      increased MCP-1 mRNA transcription. The 30 mM D-glucose induced downregulation of 
      CCR2 mRNA expression was prevented in the presence of TNFalpha. CONCLUSION: High 
      ambient glucose does not affect mesangial MCP-1 release and decreases its CCR2 
      receptor expression. However, in the presence of an inflammatory stimulus these 
      effects of high glucose are reversed and an autocrine pathway of MCP-1 develops 
      in mesangial cells.
CI  - Copyright 2002 S. Karger AG, Basel
FAU - Janssen, Ulf
AU  - Janssen U
AD  - Division of Nephrology, University of Aachen, Medizinische Hochschule, Hannover, 
      Germany.
FAU - Sowa, Eveline
AU  - Sowa E
FAU - Marchand, Petra
AU  - Marchand P
FAU - Floege, Jurgen
AU  - Floege J
FAU - Phillips, Aled O
AU  - Phillips AO
FAU - Radeke, Heinfried H
AU  - Radeke HH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Nephron
JT  - Nephron
JID - 0331777
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cell Movement/physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Culture Media, Serum-Free
MH  - *Gene Expression Regulation
MH  - Glomerular Mesangium/cytology/drug effects/*metabolism
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Up-Regulation/physiology
EDAT- 2002/10/26 04:00
MHDA- 2003/07/18 05:00
CRDT- 2002/10/26 04:00
PHST- 2002/10/26 04:00 [pubmed]
PHST- 2003/07/18 05:00 [medline]
PHST- 2002/10/26 04:00 [entrez]
AID - 65448 [pii]
AID - 10.1159/000065448 [doi]
PST - ppublish
SO  - Nephron. 2002 Dec;92(4):797-806. doi: 10.1159/000065448.