PMID- 16518346
OWN - NLM
STAT- MEDLINE
DCOM- 20060524
LR  - 20071115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 69
IP  - 5
DP  - 2006 Mar
TI  - The MCP-1/CCR2 system has direct proinflammatory effects in human mesangial 
      cells.
PG  - 856-63
AB  - Both inflammatory and haemodynamic factors have been implicated in the 
      pathogenesis of diabetic and other progressive glomerulopathies. Mesangial cell 
      exposure to mechanical stretch induces both intercellular adhesion molecule 1 
      (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression. CC Chemokine 
      receptor 2 (CCR2), the cognate MCP-1 receptor, has been recently demonstrated in 
      human mesangial cells (HMCs). We tested whether MCP-1 binding to CCR2 affects 
      ICAM-1 expression in HMCs and, secondly, if stretch-induced ICAM-1 is mediated by 
      MCP-1 via an autocrine mechanism. Serum-deprived HMCs were exposed to either 
      rh-MCP-1 (0.1-1-10-50-100 ng/ml) or mechanical stretch in the presence and in the 
      absence of RS102895, a specific CCR2 inhibitor. ICAM-1 expression was assessed 
      both by immunofluorescence and cytofluorimetry. Monocyte-HMC interaction was 
      tested by adhesion assay. CCR2 expression was studied by reverse 
      transcriptase-polymerase chain reaction, immunoblotting, and flow cytometry. HMCs 
      exposure to rh-MCP-1 induced a significant twofold increase in ICAM-1 expression 
      at 24 h, leading to enhanced monocyte adhesion. This effect occurred via the CCR2 
      receptor as CCR2 was expressed in HMCs and CCR2 blockade prevented ICAM-1 
      upregulation. Stretch-induced ICAM-1 expression was not altered by CCR2 blockade 
      and stretch significantly reduced CCR2 mRNA and protein expression via an 
      MCP-1-independent mechanism. In conclusion, stretch and MCP-1 independently 
      induce ICAM-1 expression in HMCs. Stretch-induced CCR2 downregulation may favour 
      MCP-1 paracrine activity.
FAU - Giunti, S
AU  - Giunti S
AD  - Department of Internal Medicine, University of Turin, 14 Corso AM Dogliotti, 
      10126 Turin, Italy. sara_giunti@katamail.com
FAU - Pinach, S
AU  - Pinach S
FAU - Arnaldi, L
AU  - Arnaldi L
FAU - Viberti, G
AU  - Viberti G
FAU - Perin, P C
AU  - Perin PC
FAU - Camussi, G
AU  - Camussi G
FAU - Gruden, G
AU  - Gruden G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Cell Adhesion
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Down-Regulation
MH  - Humans
MH  - Inflammation Mediators/*metabolism
MH  - Intercellular Adhesion Molecule-1/biosynthesis
MH  - Mesangial Cells/cytology/*metabolism
MH  - Monocytes/cytology
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics/*metabolism
MH  - Stress, Mechanical
EDAT- 2006/03/07 09:00
MHDA- 2006/05/25 09:00
CRDT- 2006/03/07 09:00
PHST- 2006/03/07 09:00 [pubmed]
PHST- 2006/05/25 09:00 [medline]
PHST- 2006/03/07 09:00 [entrez]
AID - S0085-2538(15)51580-9 [pii]
AID - 10.1038/sj.ki.5000197 [doi]
PST - ppublish
SO  - Kidney Int. 2006 Mar;69(5):856-63. doi: 10.1038/sj.ki.5000197.