title: 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.affiliation: Department of Medicine, Division of Rheumatology and Immunology, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: X K
authors.initials: XK
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D007249:Inflammation / Q000235:genetics; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018925:Chemokines; D051789:Proto-Oncogene Protein c-fli-1; D049452:Green Fluorescent Proteins
keywords: Fli-1; chemokines; chemotaxis; infiltration; lupus nephritis