title: Soluble receptor for advanced glycation end products alleviates nephritis in (NZB/NZW)F1 mice.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Kyu-Hyung
authors.initials: KH
authors.lastname: Park
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Kim
authors.forename: Sung-Yu
authors.initials: SY
authors.lastname: Hong
authors.forename: Soo-Kon
authors.initials: SK
authors.lastname: Lee
authors.forename: Donghoon
authors.initials: D
authors.lastname: Choi
authors.forename: Yong-Beom
authors.initials: YB
authors.lastname: Park
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008814:Mice, Inbred NZB; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016328:NF-kappa B; D011239:Prednisolone / Q000627:therapeutic use; D011507:Proteinuria; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000936:Antigen-Antibody Complex; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011239:Prednisolone; D009173:Mycophenolic Acid