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- Title
The MCP-1/CCR2 system has direct proinflammatory effects in human mesangial cells.
- Authors
Giunti, S.; Pinach, S.; Arnaldi, L.; Viberti, G.; Perin, P. C.; Camussi, G.; Gruden, G.
- Abstract
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.Kidney International (2006) 69, 856–863. doi:10.1038/sj.ki.5000197; published online 25 January 2006
- Subjects
PATHOGENIC microorganisms; PEOPLE with diabetes; CELLS; MOLECULES; MONOCYTES; PROTEINS; AUTOCRINE mechanisms
- Publication
Kidney International, 2006, Vol 69, Issue 5, p856
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/sj.ki.5000197