Fli-1 transcription factor affects inflammatory cell infiltration into the kidneys independent of autoantibodies (P4150)

Abstract

Abstract Background and Purpose: Expression levels of Fli-1, a member of the Ets family of transcription factors, are a mitigating factor in the development of nephritis in lupus model mouse. In this study, we examined the effects of reduced expression of Fli-1 on inflammatory cell infiltration into the kidneys in vivo. Methods: We generated MRL/lpr transgenic mice expressing green fluorescent protein (GFP), and isolated spleen cells from these mice. One million cells were injected into 9 Fli-1 heterozygous (+/-) and 13 wild-type (WT) MRL/lpr mice at the age of 4 to 8 months. Mice were sacrificed 18 hours after injection, kidneys were removed and frozen sections were made. Inflammatory cells with GFP were counted by immunofluorescence microscopy. The expression of chemokines in the kidney tissue was analyzed by real-time PCR. Results: The GFP positive cells were significantly higher in kidneys from WT MRL/lpr mice compared to Fli-1+/- MRL/lpr mice despite similar autoantibody titers found. We identified the majority of these cells as T cells, B cells and macrophages. Fli-1+/- MRL/lpr mice had less proteinuria and the expression level of chemokines in the kidneys had lower trends after GFP cells injection. Conclusion: Our data indicate that Fli-1 expression impacts lupus nephritis development by modulating expression of inflammatory chemokines in the kidney and infiltration of inflammatory cells independent of autoantibodies in MRL/lpr mice.