Angiotensin II Participates in Mononuclear Cell Recruitment in Experimental Immune Complex Nephritis Through Nuclear Factor-κB Activation and Monocyte Chemoattractant Protein-1 Synthesis

Abstract Angiotensin-converting enzyme (ACE) inhibitors reduce macrophage infiltration in several models of renal injury. We approached the hypothesis that angiotensin II (AngII) could be involved in inflammatory cell recruitment during renal damage through the synthesis of monocyte chemoattractant protein-1 (MCP-1). In a model of immune complex nephritis, we observed an up-regulation of renal MCP-1 (mRNA and protein) coincidentally with mononuclear cell infiltration that were markedly reduced by treatment with the ACE inhibitor quinapril. Exposure of cultured rat mesangial cells to AngII increased MCP-1 mRNA expression (2.7-fold) and synthesis (3-fold), similar to that observed with TNF-α. Since NF-κB is involved in the regulation of MCP-1 gene, we explored whether the effects of AngII were mediated through NF-κB activation. Untreated nephritic rats showed increased renal NF-κB activity (3.5-fold) that decreased in response to ACE inhibition. In mesangial cells, AngII activated NF-κB (4.3-fold), and the NF-κB inhibitor pyrrolidine dithiocarbamate abolished the AngII-induced NF-κB activation and MCP-1 gene expression. Our results suggest that AngII could participate in the recruitment of mononuclear cells through NF-κB activation and MCP-1 expression by renal cells. This could be a novel mechanism that might further explain the beneficial effects of ACE inhibitors in progressive renal diseases.