Prostaglandin EP2 and EP4 receptors modulate expression of the chemokine CCL2 (MCP-1) in response to LPS-induced renal glomerular inflammation
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Prostaglandin EP2 and EP4 receptors modulate expression of the chemokine CCL2 (MCP-1) in response to LPS-induced renal glomerular inflammation. / Zahner, Gunther; Schaper, Melanie; Panzer, Ulf; Kluger, Malte; Stahl, Rolf A K; Thaiss, Friedrich; Schneider, André.
in: BIOCHEM J, Jahrgang 422, Nr. 3, 15.09.2009, S. 563-70.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Prostaglandin EP2 and EP4 receptors modulate expression of the chemokine CCL2 (MCP-1) in response to LPS-induced renal glomerular inflammation
AU - Zahner, Gunther
AU - Schaper, Melanie
AU - Panzer, Ulf
AU - Kluger, Malte
AU - Stahl, Rolf A K
AU - Thaiss, Friedrich
AU - Schneider, André
PY - 2009/9/15
Y1 - 2009/9/15
N2 - 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.
AB - 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.
KW - Adjuvants, Immunologic
KW - Animals
KW - Blotting, Western
KW - Cell Line
KW - Chemokine CCL2
KW - Dinoprostone
KW - Enzyme-Linked Immunosorbent Assay
KW - Kidney Glomerulus
KW - Lipopolysaccharides
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Nephritis
KW - Receptors, Prostaglandin E
KW - Receptors, Prostaglandin E, EP2 Subtype
KW - Receptors, Prostaglandin E, EP4 Subtype
U2 - 10.1042/BJ20090420
DO - 10.1042/BJ20090420
M3 - SCORING: Journal article
C2 - 19570035
VL - 422
SP - 563
EP - 570
JO - BIOCHEM J
JF - BIOCHEM J
SN - 0264-6021
IS - 3
ER -