کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5555472 1559746 2017 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Investigations on the immunosuppressive activity of derivatives of mycophenolic acid in immature dendritic cells
ترجمه فارسی عنوان
تحقیقات در مورد فعالیت های سرکوب کننده ایمنی مشتق های اسید مایکوفنولی در سلول های دندریتیک نابالغ
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
چکیده انگلیسی


- Designed MPA derivatives inhibited the maturation of DC.
- Pro-inflammatory cytokines level was also reduced.
- Several compounds were more active towards IL-2 than parent MPA.
- Two acridone derivatives of MPA increased anti-inflammatory cytokines level.

The main activity of mycophenolic acid 1 (MPA) and its analogs is the inhibition of proliferation of T cells. Here, we hypothesized that MPA and its conjugates inhibits also the activity of antigen-presenting cells (APC) including dendritic cells (DCs). We tested the effect of novel amino acid derivatives of MPA and conjugates of MPA with acridines/acridones on DCs by flow cytometry, ELISA and MLR assay. Both acridines/acridone derivatives could inhibit the maturation of DC, as shown by the decreased expression of B7 family receptors. It was confirmed in the mixed leucocyte reaction (MLR), in which T cells challenged with DCs pretreated with the analogs showed decreased proliferation and reduced cytokine secretion. The most interesting activity in this series of studies, that is, the suppression of CD86 receptor expression, decreased cytokine production and suppressed mixed leucocyte reaction, exhibited (mycophenoyl-N-3-propyl)-9-acridone-4-carboxamide ester 5a and (mycophenoyl-N-5-pentyl)-9-acridone-4-carboxamide ester 5b. These compounds reduced also the secretion of IL-2 and IL-15. In addition, they increased secretion of suppressive IL-10. Equally promising results were obtained for the N-mycophenoyl-D-glutamic acid 4b, which previously gave the highest value of selectivity. Acridone derivatives of MPA are therefore good immunosuppressive drug candidates for further testing.

The selected derivatives of mycophenolic acid (MPA), a potent immunosuppressant, were investigated on their influence on maturation of dendritic cells (DCs). The tested compounds decreased concentrations of cytokines significant for immune response within allograft rejection. The most promising results were obtained in the case of acridone conjugates of MPA and N-mycophenoyl-D-glutamic acid.79

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 44, March 2017, Pages 137-142
نویسندگان
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