Interferon-gamma regulation of human renal cortical epithelial cell-derived monocyte chemotactic peptide-1

The chemoattractant signal(s) that results in the transmigration of monocytes/macrophage into the tubulointerstitium during acute inflammation is not known. Monocyte chemotactic peptide-1 (MCP-1), a recently described chemotactic cytokine, may function as both a potent monocyte chemotaxin and activator in renal inflammation. We have studied the proinflammatory conditions in which cultured human renal cortical epithelial cells (RCEC) of tubular origin may be stimulated to produce MCP-1. RCEC were stimulated in a dose-time dependent manner with: IL-1 beta (0.01 to 1.0 ng/ml), TNF (0.1 to 10 ng/ml), LPS (0.1 to 10 micrograms/ml) or INF-gamma (10-1000 U/ml). Conditioned media from RCEC stimulated with either IL-1 beta or INF-gamma produced a monocyte chemoattractant activity which was significantly suppressed with neutralizing antibody to MCP-1. Stimulation of RCEC with either IL-1 beta or INF-gamma resulted in a significant (4- to 5-fold) increase in steady state levels of MCP-1 mRNA. MCP-1 antigenic peptide in RCEC conditioned media was significantly increased over control (2- to 2.5-fold) after stimulation with either IL-1 beta or IFN-gamma. In contrast, production of interleukin-8 (IL-8), a neutrophil chemotactic cytokine, was not stimulated by IFN-gamma in RCEC. Thus, the chemokine signaling repertoire of renal tubule cells may be selectively controlled by IFN-gamma.