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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Clin+Exp+Immunol
2014 ; 177
(1
): 102-9
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The Friend leukaemia virus integration 1 (Fli-1) transcription factor affects
lupus nephritis development by regulating inflammatory cell infiltration into the
kidney
#MMPMID24580413
Sato S
; Zhang XK
Clin Exp Immunol
2014[Jul]; 177
(1
): 102-9
PMID24580413
show ga
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.