کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9007877 1122720 2005 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of mycophenolic acid on endothelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Effects of mycophenolic acid on endothelial cells
چکیده انگلیسی
Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits the activity of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo synthesis of guanosine nucleotides. MMF has been used widely in solid-organ transplantation. Increased evidence indicated that MMF exhibited beneficial effects on various types of vasculitis, for reasons that were not fully understood. Endothelial cells play a pivotal role in the pathogenesis of vasculitis. Endothelium may not only be the main target for injury, but also be able to amplify the inflammatory response by adhesion molecule expression, leukocyte adhesion, cytokine production and angiogenesis. In the present study, the effect of mycophenolic acid (MPA), the active metabolite of MMF, on human umbilical vein endothelial cells (HUVECs) was investigated. MPA markedly inhibited tumor necrosis factor-α (TNFα)-induced intercellular adhesion molecule-1 (ICAM-1) mRNA and surface expression, suppressed TNFα-induced neutrophils adhesion to endothelial cells, and reduced TNFα-induced interleukin-6 (IL-6) secretion. The inhibitory effects of MPA on ICAM-1 surface expression and IL-6 secretion were not attenuated by addition of guanosine, implying that inhibition of these processes were not due to intracellular guanosine nucleotides depletion. MPA also decreased angiogenesis of endothelial cells in three-dimensional collagen gel culture system, reduced the migration in a wounded monolayer of endothelial cells, and inhibited the proliferation of endothelial cells. In conclusion, MPA exhibited multifarious effects on endothelial cells including inhibition of ICAM-1 expression, neutrophil attachment, IL-6 secretion, and the process of angiogenesis, which might contribute to the efficacy of MMF in the treatment of vasculitis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 5, Issue 6, June 2005, Pages 1029-1039
نویسندگان
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