Endothelin-1, Endothelin-2 and Endothelin-3 Induced Expression of Monocyte Chemoattractant Protein-1 in Rat Mesangial Cells / 대한신장학회잡지

ABSTRACT

BACKGROUND: Monocyte chemoattractant protein- 1 (MCP-1) is an important mediator for monocyte/ macrophage infiltration in various inflammatory renal diseases and is produced by renal cells. In the process of renal diseases, endothelin-1 (ET-1) is known to play an active role in cell growth, inflammation and fibrosis. The aim of this study was to investigate whether three isoforms of endothelin regulate MCP-1 expression in cultured mesangial cells. METHODS: Mesangial cells were incubated with or without various doses of ET-1, ET-2 or ET-3. To determine the monocyte chemotactic activity, chemotaxis assay was performed in modified Boyden chambers using freshly isolated human monocytes. MCP-1 mRNA expression in mesangial cells was measured by Northern blot analysis. RESULTS: ET-1, ET-2 and ET-3 stimulated monocyte chemotactic activity released from mesangial cells in a dose-dependent manner. ET-1, ET-2 and ET-3 also stimulated MCP-1 mRNA expression in a time-dependent manner, which was seen as early as 4 hours and was maintained up to 24 hours. CONCLUSION: These data suggest that ET-1, ET- 2 and ET-3 stimulate MCP-1 expression in mesangial cells and may contribute to the monocyte/ macrophage infiltration in inflammatory renal diseases.