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Attenuation of nephritis in lupus-prone mice by thalidomide

Authors
 Sang-Won Lee ; Yong-Beom Park ; Beom Seok Kim ; Kyu Hun Choi ; Soo-Kon Lee ; Kyu-Hyung Park ; Jaeseok Yang 
Citation
 Rhuematology, Vol.51(12) : 2131~2140, 2012 
Journal Title
 Rhuematology 
ISSN
 1462-0324 
Issue Date
2012
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/91814
DOI
10.1093/rheumatology/kes227
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
Yonsei Authors
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Link
 http://rheumatology.oxfordjournals.org/content/51/12/2131.long
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