The pro-inflammatory chemokine CCL2 [chemokine (Cys-Cys motif) ligand 2; also known as MCP-1 (monocyte chemotactic protein-1)] is up-regulated in the glomerular compartment during the early phase of LPS (lipopolysaccharide)-induced nephritis. This up-regulation also occurs in cultured MCs (mesangial cells) and is more pronounced in MCs lacking the PGE2 (prostaglandin E2) receptor EP2 or in MCs treated with a prostaglandin EP4 receptor antagonist. To examine a possible feedback mechanism of EP receptor stimulation on CCL2 expression, we used an in vitro model of MCs with down-regulated EP receptor expression. Selectively overexpressing the various EP receptors in these cells then allows the effects on the LPS-induced CCL2 expression to be examined. Cells were stimulated with LPS and CCL2 gene expression was examined and compared with LPS-stimulated, mock-transfected PTGS2 [prostaglandin-endoperoxide synthase 2, also known as COX-2 (cyclo-oxygenase-2)]-positive cells. Overexpression of EP1, as well as EP3, had no effect on LPS-induced Ccl2 mRNA expression. In contrast, overexpression of EP2, as well as EP4, significantly decreased LPS-induced CCL2 expression. These results support the hypothesis that PTGS2-derived prostaglandins, when strongly induced, counter-balance inflammatory processes through the EP2 and EP4 receptors in MCs.
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Research Article|
August 27 2009
Prostaglandin EP2 and EP4 receptors modulate expression of the chemokine CCL2 (MCP-1) in response to LPS-induced renal glomerular inflammation
Gunther Zahner;
Gunther Zahner
1
1Zentrum Innere Medizin III, Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany
1To whom correspondence should be addressed (email zahner@uke.uni-hamburg.de).
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Melanie Schaper;
Melanie Schaper
1Zentrum Innere Medizin III, Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany
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Ulf Panzer;
Ulf Panzer
1Zentrum Innere Medizin III, Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany
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Malte Kluger;
Malte Kluger
1Zentrum Innere Medizin III, Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany
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Rolf A. K. Stahl;
Rolf A. K. Stahl
1Zentrum Innere Medizin III, Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany
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Friedrich Thaiss;
Friedrich Thaiss
1Zentrum Innere Medizin III, Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany
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André Schneider
André Schneider
1Zentrum Innere Medizin III, Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany
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Publisher: Portland Press Ltd
Received:
March 12 2009
Revision Received:
June 17 2009
Accepted:
July 02 2009
Accepted Manuscript online:
July 02 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 422 (3): 563–570.
Article history
Received:
March 12 2009
Revision Received:
June 17 2009
Accepted:
July 02 2009
Accepted Manuscript online:
July 02 2009
Citation
Gunther Zahner, Melanie Schaper, Ulf Panzer, Malte Kluger, Rolf A. K. Stahl, Friedrich Thaiss, André Schneider; Prostaglandin EP2 and EP4 receptors modulate expression of the chemokine CCL2 (MCP-1) in response to LPS-induced renal glomerular inflammation. Biochem J 15 September 2009; 422 (3): 563–570. doi: https://doi.org/10.1042/BJ20090420
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