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Attenuation of nephritis in lupus-prone mice by thalidomide

Authors
 Sang-Won Lee  ;  Yong-Beom Park  ;  Jaeseok Yang  ;  Kyu-Hyung Park  ;  Soo-Kon Lee  ;  Kyu Hun Choi  ;  Beom Seok Kim 
Citation
 RHEUMATOLOGY , Vol.51(12) : 2131-2140, 2012 
Journal Title
 RHEUMATOLOGY 
ISSN
 0080-2727 
Issue Date
2012
MeSH
Animals ; Anti-Inflammatory Agents/administration & dosage ; Anti-Inflammatory Agents/pharmacology* ; Anti-Inflammatory Agents/toxicity ; Antigen-Antibody Complex/metabolism ; DNA/metabolism ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Glomerulonephritis/pathology ; Glomerulonephritis/prevention & control ; Immunoglobulin G/metabolism ; Immunosuppressive Agents/pharmacology ; Lupus Nephritis/blood ; Lupus Nephritis/pathology ; Lupus Nephritis/prevention & control* ; Mice ; Mice, Inbred NZB ; Mycophenolic Acid/analogs & derivatives ; Mycophenolic Acid/pharmacology ; Prednisolone/administration & dosage ; Prednisolone/pharmacology ; Proteinuria/prevention & control ; Survival Rate ; Thalidomide/administration & dosage ; Thalidomide/pharmacology* ; Thalidomide/toxicity
Keywords
thalidomide ; NZB/WF1 mice ; LN
Abstract
OBJECTIVES: Thalidomide has various effects, such as immune modulation, anti-angiogenicity, anti-inflammation and anti-proliferation. Moreover, thalidomide modulates the activity of NF-κB, which can up-regulate the expression of downstream genes involved in the pathophysiology of LN. Here we investigated the efficacy of thalidomide monotherapy or thalidomide plus prednisolone (PL) on nephritis in NZB/WF1 mice at different doses and compared both with a combination therapy of MMF plus PL. METHODS: Forty-three female NZB/WF1 mice were divided into eight groups (untreated; 1.7, 5 or 10 mg/kg of thalidomide alone; 1.7, 5 or 10 mg/kg of thalidomide plus 1.5 mg/kg of PL and 33.3 mg/kg of MMF plus PL). Proteinuria and histological damage were evaluated. Immune complex deposition and nuclear translocation of NF-κB in kidney tissues were assessed by immunofluorescence staining. Serum concentrations of anti-dsDNA and IgG subclasses were also measured. RESULTS: In comparison with untreated mice, mice treated with 10 mg/kg of thalidomide monotherapy showed a significant decrease in proteinuria and significantly lower glomerular and tubular damage scores, comparable to 5 or 10 mg/kg of thalidomide plus PL or MMF plus PL. Also, treatment with 10 mg/kg of thalidomide significantly decreased immune complex accumulation, reduced the serum concentration of anti-dsDNA, IgG2a and IgG2b and inhibited nuclear translocation of NF-κB in kidney tissues, comparable to standard therapy for LN. CONCLUSION: These data suggest that thalidomide might play an anti-inflammatory role in the pathophysiology of LN, and it could serve as a complementary therapy to standard induction regimens for refractory LN.
Full Text
http://rheumatology.oxfordjournals.org/content/51/12/2131.long
DOI
22923758
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
Park, Kyu Hyung(박규형)
Park, Yong Beom(박용범)
Lee, Sang Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
Lee, Soo Kon(이수곤)
Choi, Kyu Hun(최규헌) ORCID logo https://orcid.org/0000-0003-0095-9011
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91814
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