Abstract
Abstract Fli-1, a member of the Ets family of transcription factors, is highly expressed in immune cells and endothelial cells and is implicated in the development of nephritis in murine models of systemic lupus erythematosus (SLE). Expression of monocyte chemotactic protein-1 (MCP-1) play an important role in the inflammation responses. In this study, we examined the role of Fli-1 on production of MCP-1 in endothelial cells. We found expression of MCP-1 was significantly reduced in endothelial cells isolated from Fli-1 heterozygous knockout NZM2410 mice (Fli1+/-; Fli-1 homozygous knockout is embryonic lethal) after stimulation with Lipopolysaccharides (LPS) compared with endothelial cells isolated from wild-type controls. The expression of Fli-1 protein was significantly reduced and the production of MCP-1 was significantly decreased in endothelial cells transfected with specific Fli-1 siRNA compared to cells transfected with negative control siRNA. We demonstrated that Fli-1 directly binds to the promotor of MCP-1 by Chromatin Immunoprecipitation (ChIP) assay. Our data indicate that transcription factor Fli-1 can binds to the promoter of MCP-1 and directly regulates the expression of inflammatory chemokine MCP-1.
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