Prostaglandin EP2 and EP4 receptors modulate expression of the chemokine CCL2 (MCP-1) in response to LPS-induced renal glomerular inflammation.

Full Abstract

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.

Author information

Author/s: Zahner, Gunther (G); Schaper, Melanie (M); Panzer, Ulf (U); Kluger, Malte (M); Stahl, Rolf A K (RA); Thaiss, Friedrich (F); Schneider, André (A);

Affiliation: Zentrum Innere Medizin III, Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany. zahner(-atsign-)uke.uni-hamburg.de

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Biochemical journal (Biochem J), published in England. (Language: eng)

Reference: 2009-Sep; vol 422 (issue 3) : pp 563-70

Dates: Created 2009/08/24; Completed 2009/09/16;

PMID: 19570035, status: MEDLINE (last retrieved date: 9/16/2009)

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Kidney Glomerulus - drug effects; metabolism
Lipopolysaccharides - pharmacology
Mice
Mice, Inbred C57BL
Mice, Knockout
Nephritis - chemically induced; metabolism
Receptors, Prostaglandin E - genetics; physiology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Adjuvants, Immunologic (0) ; Chemokine CCL2 (0) ; Lipopolysaccharides (0) ; Receptors, Prostaglandin E (0) ; prostaglandin E2 receptor, EP4 subtype (0) ; prostaglandin EP2 receptor (0) ; Dinoprostone (363-24-6)

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