Selective lymphocyte inhibition by FTY720 slows the progressive course of chronic anti-thy 1 glomerulosclerosis

Abstract

Lymphocyte depletion by FTY720 limits the progression of anti-thy 1-induced glomerulosclerosis toward chronic tubulointerstitial fibrosis and renal insufficiency. The data suggest that lymphocytes actively participate in the progression of chronic experimental kidney disease, and that FTY720 may be a novel approach to slow the progressive course of human chronic renal diseases.

Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced chronic glomerulosclerosis of the rat

“…Glomeruli from individual rats were isolated by a graded sieving technique (160-, 125-, and 71-m mesh metal sieves), as described previously (17,22,27). For cultures of renal cortical tissue, a piece of cortical tissue was weighed and minced extensively with a razor blade.…”

“…After 48-h incubation at 37°C/5% CO 2, supernatants were harvested and stored at Ϫ70°C until analysis of TGF-␤1 or TIMP-1 content. TGF-␤1 and TIMP-1 content of the culture supernatant was measured after acid activation, using commercially available ELISA kits (TGF-␤1 and TIMP-1 Duoset, R&D Systems, Wiesbaden, Germany) according to the manufacturer's instructions (17,22,27). Three samples from each rat were analyzed.…”

Rosuvastatin is additive to high-dose candesartan in slowing progression of experimental mesangioproliferative glomerulosclerosis

“…Progression in chronic anti-thy1 GS is not primarily immune mediated. It is rather an experimental paradigm for a "one-hit, self-progressing kidney disease," as it is seen in patients with deteriorating renal function and a transient glomerulonephritic episode in the past (18). Control animals with and without uninephrectomy were injected with equal volumes of PBS only.…”

The lymphocyte migration inhibitor FTY720 attenuates experimental hypertensive nephropathy

“…In a model of antibody-induced, chronic-progressive renal fibrosis, i.e., anti-thy1-induced chronic glomerulosclerosis, we have previously reported that selective inhibition of lymphocyte migration into the diseased kidney by FTY720 significantly limited the progressive course of the disease toward glomerulosclerosis and tubulointerstitial fibrosis (21). FTY720 {fingolimod; 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride} is a novel and potent lymphocyte-specific immunomodulator and has currently been tested in phase III studies for the treatment of multiple sclerosis (3,10).…”