Soluble receptor for advanced glycation end products alleviates nephritis in (NZB/NZW)F1 mice

Sang Won Lee, Kyu Hyung Park, Sungha Park, Ji Hye Kim, Sung Yu Hong, Soo Kon Lee, Donghoon Choi, YongBeom Park

Research output: Contribution to journalArticle

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Abstract

Objective To investigate the efficacy of different doses of the soluble form of the receptor for advanced glycation end products (sRAGE) (conjugated to the Fc portion of immunoglobulin) in the treatment of nephritis in lupus-prone mice, in comparison with the efficacy of combination therapy with mycophenolate mofetil plus prednisolone. Methods Twenty-eight female (NZB/NZW)F1 mice were divided into 5 groups (untreated, sRAGE [dose groups of 0.5, 1, or 2 μg], or mycophenolate mofetil plus prednisolone). Proteinuria and histologic damage were evaluated. Immune complex deposition and the nuclear translocation of NF-κB in the kidney tissue were assessed by immunofluorescence staining. Serum concentrations of anti-double-stranded DNA (anti-dsDNA) and IgG subclasses were also measured. The population of T cells was evaluated using a fluorescence-activated cell sorter, and expression of intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 in the kidney tissue was assessed by immunohistochemical staining. Results In comparison with untreated mice, mice treated with 1 or 2 μg sRAGE showed significantly reduced proteinuria and attenuated histologic renal damage, with efficacy comparable to that of combination therapy. Treatment with 2 μg sRAGE significantly reduced immune complex deposition and decreased the serum concentrations of anti-dsDNA, IgG2a, IgG2b, and IgG3. In addition, sRAGE interrupted the nuclear translocation of NF-κB in the kidney, resulting in reduction in the expression of downstream genes of NF-κB in vivo and in vitro. Furthermore, sRAGE effectively modified T cell populations. Conclusion Treatment with 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 has antiinflammatory effects on the pathophysiology of lupus nephritis and could serve as a potent new therapy for this disease.

Original languageEnglish
Pages (from-to)1902-1912
Number of pages11
JournalArthritis and Rheumatism
Volume65
Issue number7
DOIs
Publication statusPublished - 2013 Jul 1

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Nephritis
Lupus Nephritis
Mycophenolic Acid
Kidney
Prednisolone
Antigen-Antibody Complex
Proteinuria
Therapeutics
Immunoglobulin G
Staining and Labeling
Immunoglobulin Fc Fragments
T-Lymphocytes
Vascular Cell Adhesion Molecule-1
Advanced Glycosylation End Product-Specific Receptor
Serum
Population
Fluorescent Antibody Technique
Anti-Inflammatory Agents
Fluorescence
Gene Expression

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Lee, Sang Won ; Park, Kyu Hyung ; Park, Sungha ; Kim, Ji Hye ; Hong, Sung Yu ; Lee, Soo Kon ; Choi, Donghoon ; Park, YongBeom. / Soluble receptor for advanced glycation end products alleviates nephritis in (NZB/NZW)F1 mice. In: Arthritis and Rheumatism. 2013 ; Vol. 65, No. 7. pp. 1902-1912.
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abstract = "Objective To investigate the efficacy of different doses of the soluble form of the receptor for advanced glycation end products (sRAGE) (conjugated to the Fc portion of immunoglobulin) in the treatment of nephritis in lupus-prone mice, in comparison with the efficacy of combination therapy with mycophenolate mofetil plus prednisolone. Methods Twenty-eight female (NZB/NZW)F1 mice were divided into 5 groups (untreated, sRAGE [dose groups of 0.5, 1, or 2 μg], or mycophenolate mofetil plus prednisolone). Proteinuria and histologic damage were evaluated. Immune complex deposition and the nuclear translocation of NF-κB in the kidney tissue were assessed by immunofluorescence staining. Serum concentrations of anti-double-stranded DNA (anti-dsDNA) and IgG subclasses were also measured. The population of T cells was evaluated using a fluorescence-activated cell sorter, and expression of intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 in the kidney tissue was assessed by immunohistochemical staining. Results In comparison with untreated mice, mice treated with 1 or 2 μg sRAGE showed significantly reduced proteinuria and attenuated histologic renal damage, with efficacy comparable to that of combination therapy. Treatment with 2 μg sRAGE significantly reduced immune complex deposition and decreased the serum concentrations of anti-dsDNA, IgG2a, IgG2b, and IgG3. In addition, sRAGE interrupted the nuclear translocation of NF-κB in the kidney, resulting in reduction in the expression of downstream genes of NF-κB in vivo and in vitro. Furthermore, sRAGE effectively modified T cell populations. Conclusion Treatment with 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 has antiinflammatory effects on the pathophysiology of lupus nephritis and could serve as a potent new therapy for this disease.",
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Soluble receptor for advanced glycation end products alleviates nephritis in (NZB/NZW)F1 mice. / Lee, Sang Won; Park, Kyu Hyung; Park, Sungha; Kim, Ji Hye; Hong, Sung Yu; Lee, Soo Kon; Choi, Donghoon; Park, YongBeom.

In: Arthritis and Rheumatism, Vol. 65, No. 7, 01.07.2013, p. 1902-1912.

Research output: Contribution to journalArticle

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AU - Lee, Sang Won

AU - Park, Kyu Hyung

AU - Park, Sungha

AU - Kim, Ji Hye

AU - Hong, Sung Yu

AU - Lee, Soo Kon

AU - Choi, Donghoon

AU - Park, YongBeom

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N2 - Objective To investigate the efficacy of different doses of the soluble form of the receptor for advanced glycation end products (sRAGE) (conjugated to the Fc portion of immunoglobulin) in the treatment of nephritis in lupus-prone mice, in comparison with the efficacy of combination therapy with mycophenolate mofetil plus prednisolone. Methods Twenty-eight female (NZB/NZW)F1 mice were divided into 5 groups (untreated, sRAGE [dose groups of 0.5, 1, or 2 μg], or mycophenolate mofetil plus prednisolone). Proteinuria and histologic damage were evaluated. Immune complex deposition and the nuclear translocation of NF-κB in the kidney tissue were assessed by immunofluorescence staining. Serum concentrations of anti-double-stranded DNA (anti-dsDNA) and IgG subclasses were also measured. The population of T cells was evaluated using a fluorescence-activated cell sorter, and expression of intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 in the kidney tissue was assessed by immunohistochemical staining. Results In comparison with untreated mice, mice treated with 1 or 2 μg sRAGE showed significantly reduced proteinuria and attenuated histologic renal damage, with efficacy comparable to that of combination therapy. Treatment with 2 μg sRAGE significantly reduced immune complex deposition and decreased the serum concentrations of anti-dsDNA, IgG2a, IgG2b, and IgG3. In addition, sRAGE interrupted the nuclear translocation of NF-κB in the kidney, resulting in reduction in the expression of downstream genes of NF-κB in vivo and in vitro. Furthermore, sRAGE effectively modified T cell populations. Conclusion Treatment with 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 has antiinflammatory effects on the pathophysiology of lupus nephritis and could serve as a potent new therapy for this disease.

AB - Objective To investigate the efficacy of different doses of the soluble form of the receptor for advanced glycation end products (sRAGE) (conjugated to the Fc portion of immunoglobulin) in the treatment of nephritis in lupus-prone mice, in comparison with the efficacy of combination therapy with mycophenolate mofetil plus prednisolone. Methods Twenty-eight female (NZB/NZW)F1 mice were divided into 5 groups (untreated, sRAGE [dose groups of 0.5, 1, or 2 μg], or mycophenolate mofetil plus prednisolone). Proteinuria and histologic damage were evaluated. Immune complex deposition and the nuclear translocation of NF-κB in the kidney tissue were assessed by immunofluorescence staining. Serum concentrations of anti-double-stranded DNA (anti-dsDNA) and IgG subclasses were also measured. The population of T cells was evaluated using a fluorescence-activated cell sorter, and expression of intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 in the kidney tissue was assessed by immunohistochemical staining. Results In comparison with untreated mice, mice treated with 1 or 2 μg sRAGE showed significantly reduced proteinuria and attenuated histologic renal damage, with efficacy comparable to that of combination therapy. Treatment with 2 μg sRAGE significantly reduced immune complex deposition and decreased the serum concentrations of anti-dsDNA, IgG2a, IgG2b, and IgG3. In addition, sRAGE interrupted the nuclear translocation of NF-κB in the kidney, resulting in reduction in the expression of downstream genes of NF-κB in vivo and in vitro. Furthermore, sRAGE effectively modified T cell populations. Conclusion Treatment with 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 has antiinflammatory effects on the pathophysiology of lupus nephritis and could serve as a potent new therapy for this disease.

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