کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5833097 | 1122618 | 2013 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
11β-Hydroxysteroid dehydrogenase 1 inhibition attenuates collagen-induced arthritis
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
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چکیده انگلیسی
11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) plays an important role in inflammation. However, the role of 11β-HSD1 in rheumatoid arthritis (RA) remains unknown. The purpose of this study was to evaluate the therapeutic effects of a selective 11β-HSD1 inhibitor BVT-2733 in collagen-induced arthritis (CIA) and its underlying mechanisms. CIA mice were treated with BVT-2733 (100 mg/kg, orally) or vehicle twice daily for 2 weeks. Arthritis score and joint histology were investigated. The levels of pro-inflammatory cytokines as well as anti-type II collagen antibody (anti-CII) were detected by ELISA. Western blot analysis was used to assess the activation of NF-κB and NLRP1 inflammasome in joint tissues and in human RA synovial cells. BVT-2733 treatment attenuated the arthritis severity and anti-CII level in CIA mice. BVT-2733 also decreased the levels of serum TNF-α, IL-1β, IL-6 and IL-17. BVT-2733 treatment also significantly reduced synovial inflammation and joint destruction. NF-κB activation and NLRP1 inflammasome assembly were also inhibited in arthritic joints and human RA synovial cells. In conclusion, BVT-2733 exhibits an anti-inflammatory effect on CIA. This protective effect is, at least partly, mediated by inhibition of the NF-κB and NLRP1 inflammasome signaling pathways. 11β-HSD1 inhibition may represent a potential therapeutic target for RA patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 17, Issue 3, November 2013, Pages 489-494
Journal: International Immunopharmacology - Volume 17, Issue 3, November 2013, Pages 489-494
نویسندگان
Lei Zhang, Yubo Dong, Fangpeng Zou, Min Wu, Changchun Fan, Yaohai Ding,