The Friend leukaemia virus integration 1 (Fli-1) transcription factor affects lupus nephritis development by regulating inflammatory cell infiltration into the kidney.

Abstract

The transcription factor Friend leukaemia virus integration 1 (Fli-1) is implicated in the pathogenesis of systemic lupus erythematosus in both human patients and murine models of lupus. Murphy Roths large (MRL)/lpr mice and New Zealand mixed (NZM)2410 mice, murine models of lupus, with decreased expression of Fli-1 had significantly prolonged survival and reduced nephritis. Lupus nephritis is a major cause of mortality and morbidity in patients, and inflammatory cell infiltration plays a key role in the development of the disease. To study how the expression of Fli-1 affects the infiltration of inflammatory cells into the kidneys, we generated congenic enhanced green fluorescent protein (GFP) transgenic MRL/lpr mice. A significantly increased number of GFP-expressing inflammatory cells infiltrated the kidneys of wild-type MRL/lpr mice compared to Fli-1 heterozygous (Fli-1(+/-)) MRL/lpr mice after injection of GFP(+) cells. Expression of inflammatory chemokine mRNA, including chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4 and CCL5, was significantly lower in the kidneys from Fli-1(+/-) MRL/lpr mice compared to wild-type littermates. Numbers of infiltrated cells into the kidneys correlate with expression levels of CCL2, CCL4 and CCL5, but not the titres of anti-dsDNA autoantibodies in these mice. Significantly increased inflammatory cells from wild-type MRL/lpr mice infiltrated into kidneys compared to the cells from Fli-1(+/-) MRL/lpr mice. The chemotaxis of inflammatory cells from Fli-1(+/-) MRL/lpr mice towards each chemokine was decreased significantly compared to inflammatory cells from wild-type MRL/lpr mice in the transwell migration assay in vitro. Our results indicate that Fli-1 affects lupus nephritis development by regulating the expression of chemokines in the kidney and the migration of inflammatory cells.

• Authors: S Sato, X K Zhang
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 177 Issue 1 Pg. 102-9 (Jul 2014) ISSN: 1365-2249 [Electronic] England
• PMID: 24580413 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2014 British Society for Immunology.

Chemical References

• Chemokines
• Proto-Oncogene Protein c-fli-1
• Green Fluorescent Proteins

Topics

• Animals
• Cell Movement (genetics)
• Cells, Cultured
• Chemokines (genetics, metabolism)
• Chemotaxis (genetics)
• Disease Models, Animal
• Gene Expression Regulation (genetics, immunology)
• Green Fluorescent Proteins (genetics)
• Humans
• Immunotherapy
• Inflammation (genetics)
• Kidney (immunology, pathology)
• Lupus Nephritis (genetics, immunology)
• Mice
• Mice, Inbred MRL lpr
• Mice, Transgenic
• Proto-Oncogene Protein c-fli-1 (genetics, metabolism)