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 systemic lupus erythematosus (SLE) in both human patients and mouse models. Increased expression of IL-6 is also involved in the SLE and other autoimmune disease development. We examined the role of Fli-1 on production of IL-6 in this study. We found expression of IL-6 was significantly reduced in sera from Fli-1 heterozygous knockout MRL/lpr mice (Fli1+/-; Fli-1 homozygous knockout is embryonic lethal), a murine model of lupus, compared to wild-type littermates. The production of IL-6 were significantly decreased in endothelial cells transfected with specific Fli-1 siRNA compared to cells transfected with negative control siRNA after LPS stimulation. We demonstrated that Fli-1 directly binds to the IL-6 promoter by Chromatin Immunoprecipitation (ChIP) assay and transient transfection assays show that Fli-1 drives transcription from the IL-6 promoter in a dose-dependent manner. Our data indicate that transcription factor Fli-1 binds to the promoter of IL-6 and directly regulates the expression of IL-6.
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