کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2831953 1163821 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Helenalin suppresses essential immune functions of activated CD4+ T cells by multiple mechanisms
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Helenalin suppresses essential immune functions of activated CD4+ T cells by multiple mechanisms
چکیده انگلیسی

Helenalin is a naturally occuring sesquiterpene lactone extracted from Arnica montana and Arnica chamissonis ssp. foliosa. Helenalin and its derivatives are known for anti-cancer and anti-inflammatory effects via inhibiting NF-κB and telomerase activity and impairing protein and DNA synthesis, suggesting that helenalin is a potential candidate for the treatment of deregulated and unwanted T cell-mediated immune responses. Here we show that helenalin induces apoptosis in activated CD4+ T cells by triggering the mitochondrial pathway of apoptosis. Induction of apoptosis is accompanied by rapid stabilization of p53, nuclear localization of p53 and AIF, and an increase in ROS production that results in loss of mitochondrial membrane potential (ΔΨm). Activated CD4+ T cells which survive exposure to helenalin undergo inhibition of proliferation by induction of G2/M cell cycle arrest. Cell cycle arrest is accompanied by the accumulation of cell cycle regulator proteins p21WAF/CIP1, p2KIP1 and cyclin D2, whereas abundance of cyclin A and B1 is decreased. Cell surface expression of the activation-associated receptors CD25, CD27, CD28, CD120b as well as production of IL-2 are impaired. Transcriptional activation of genes encoding for CD25, IL-2 and IFN-γ is mediated by transcription factors of the NFAT family, and we demonstrate that helenalin suppresses nuclear translocation of NFATc2 in activated CD4+ T cells. Thus, helenalin can be defined as a new immunosuppressive compound suited for the treatment of deregulated and unwanted T cell-mediated immune responses.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 46, Issue 15, September 2009, Pages 2892–2901
نویسندگان
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