The pro-inflammatory chemokine CCL2 (MCP-1) is upregulated in the glomerular compartment during the early phase of LPS-induced nephritis. This upregulation also appears in cultured mesangial cells (MC) and is more pronounced in MC lacking the prostaglandin EP2 receptor or in MC treated with a prostaglandin EP4 receptor antagonist. To examine a possible feedback of EP receptor stimulation on CCL2 expression, we chose an in vitro model in MC with down regulated EP receptor expression. By selective overexpression of EP receptors in these cells, their effects on LPS-induced CCL2 expression were examined. Cells were stimulated with LPS and CCL2 gene expression was examined and compared to LPS stimulated, mock transfected COX-2+ 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 receptors significantly decreased LPS-induced CCL2 expression. These results support the hypothesis that COX-2 derived prostaglandins, when strongly induced, counter-balanced inflammatory processes through EP2 and EP4 receptors in MC.
