Session Title: Systemic Lupus Erythematosus - Animal Models
Session Type: Abstract Submissions (ACR)
The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor that interacts with multiple ligands such as high mobility group box 1 (HMGB1) and is involved in various innate immune responses. The soluble form of RAGE (sRAGE) can bind to RAGE-ligands in the extracellular space, and thus competitively inhibit the binding of ligands to the membrane-bound form of RAGE (mRAGE), resulting in a reduction of the inflammation induced by NF-κB activation. We investigated the efficacy of different doses of the Fc-portion-conjugated sRAGE on nephritis in lupus-prone mice in comparison with the efficacy of combination therapy of mycophenolate mofetil plus prednisolone.
Twenty-eight female NZB/WF1 mice were divided into five groups (untreated; 0.5, 1, 2 μg of sRAGE; mycophenolate mofetil plus prednisolone). Proteinuria and histological damage were evaluated. Immune-complex deposition and the nuclear translocation of NF-κB in kidney tissues were assessed by immunofluorescence staining. Serum concentrations of anti-dsDNA and IgG subclasses were also measured. The population of T cells was evaluated using a fluorescence-activated cell sorter and ICAM-1 and VCAM-1 expression in kidney tissues was assessed by immunohistochemical staining.
In comparison with untreated mice, mice treated with 1 or 2 μg of sRAGE showed significantly reduced proteinuria and improved histological renal damage, with efficacy comparable to that of combination therapy. Treatment with 1 or 2 μg of sRAGE significantly reduced immune-complex accumulation; decreased the serum concentrations of anti-dsDNA, IgG2a, IgG2b and IgG3; and interrupted the nuclear translocation of NF-κB in kidney tissues, leading to reduced ICAM-1 and VAM-1 expression. Furthermore, sRAGE effectively modified T cell populations.
sRAGE significantly improved nephritis in lupus-prone mice, with efficacy comparable to that of standard induction treatment for lupus nephritis. These data suggest that sRAGE have anti-inflammatory effects in lupus nephritis pathophysiology and could serve as a potent additional therapy for lupus nephritis.
S. W. Lee,
K. H. Park,
J. H. Kim,
S. Y. Hong,
S. K. Lee,
Y. B. Park,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/soluble-receptor-for-advanced-glycation-end-products-alleviates-nephritis-in-nzbwf1-mice/