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10.1002/art.38818

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suck abstract from ncbi


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pmid25155007      Arthritis+Rheumatol 2014 ; 66 (12): 3436-44
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  • A critical role for the transcription factor Fli-1 in lupus development by regulating expression of Interleukin 6 #MMPMID25155007
  • Sato S; Richard ML; Brandon D; Jones Buie JN; Oates J; Gilkeson G; Zhang XK
  • Arthritis Rheumatol 2014[Dec]; 66 (12): 3436-44 PMID25155007show ga
  • Objective: The Fli-1 transcription factor is implicated in the pathogenesis of systemic lupus erythematosus (SLE) in both human patients and animal models. Dysregulation of interleukin 6 (IL-6) is also associated with SLE. We investigated whether Fli-1 directly regulates the expression of IL-6. Methods: Sera were collected from wild-type and Fli-1 heterozygous (Fli-1+/?) MRL/lpr mice and the concentration of IL-6 was measured by ELISA. Expression of IL-6 in the kidney was measured by real-time PCR. T cells were isolated from wild-type and Fli-1+/? MRL/lpr mice and stimulated with CD3/CD28 beads, and the concentration of IL-6 in the supernatants was measured by ELISA. MS1 endothelial cells were transfected with Fli-1 and control siRNA, and the production of IL-6 was compared after lipopolysaccharides (LPS) stimulation. A chromatin immunoprecipitation (ChIP) assay was performed to determine whether Fli-1binds to the IL-6 promoter region. Transient transfections with the NIH 3T3 cell line were performed to study if Fli-1 regulates the expression of IL-6. Results: Fli-1+/? MRL/lpr mice had significantly decreased IL-6 in sera and reduced expression of IL-6 in kidneys compared to wild-type littermates. The T cells isolated from Fli-1+/? MRL/lpr mice produced less IL-6. Inhibiting the expression of Fli-1 in endothelial cells resulted in reduced production of IL-6. The ChIP assay revealed direct binding of Fli-1 to three regions within the IL-6 promoter. Fli-1 activated transcription from the IL-6 promoter in a dose-dependent manner. Conclusion: Fli-1 directly regulates IL-6 expression as one of possible mechanisms for the protective effect in lupus of decreased Fli-1 expression.
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