کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5832132 1122593 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Therapeutic targeting of BET protein BRD4 delays murine lupus
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Therapeutic targeting of BET protein BRD4 delays murine lupus
چکیده انگلیسی


- JQ1 treatment significantly attenuated the nephritis, anti-dsDNA, and proinflammatory mediators.
- JQ1 improved the survival of lupus mice.
- In vitro, BAFF, IL-1β, IL-6, and IL-17 were inhibited by JQ1.
- The immune complex-mediated activation of human monocytes in vitro was inhibited by JQ1.

BRD4 is a member of the BET (bromodomain and extraterminal domain) family proteins that can bind acetylated histones and influence transcription, which are considered as potential therapeutic targets in many distinct diseases. And the BET inhibitor JQ1 has been proven to be effective in suppressing multiple inflammatory and autoimmune diseases. This study aimed to examine the therapeutic potential of JQ1 on a lupus model, MRL-lpr mice. Ten-week-old MRL-lpr mice were treated with JQ1 (oral administration of 200 mg/kg) or vehicle for 8 weeks. The proteinuria, nephritic damage, serum biochemistry, autoantibodies and cytokines were examined. Splenocytes of MRL-lpr mice were isolated for in vitro experiments. Treatment with JQ1 significantly attenuated the progression of proteinuria and nephritis. The serum concentrations of anti-dsDNA antibody as well as B-cell activating factor (BAFF), interleukin (IL)-1β, IL-6, IL-17 and INF-γ were inhibited, and IL-10 augmented by JQ1. Importantly, JQ1 improved the survival of lupus mice. In vitro, BAFF, IL-1β, IL-6, IL-17 and INF-γ were inhibited, and IL-10 augmented by JQ1 (500 nM) in the cultures of splenocytes from diseased MRL-lpr mice, which was further supported by a significant reduction in immune complex-mediated activation of human monocytes in vitro by JQ1. Taken together, JQ1 effectively alleviates lupus in MRL-lpr mice by suppressing BAFF, pro-inflammatory cytokines and autoimmunity, supporting the therapeutic value of JQ1 in lupus disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 29, Issue 2, December 2015, Pages 314-319
نویسندگان
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