کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5833467 1122624 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Halofuginone suppresses T cell proliferation by blocking proline uptake and inducing cell apoptosis
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Halofuginone suppresses T cell proliferation by blocking proline uptake and inducing cell apoptosis
چکیده انگلیسی


- Halofuginone induced apoptosis in T cells in the response to stimulation of TCR and IL-2 via amino acid starvation response.
- The supplement of proline rescued the pro-apoptotic activity of halofuginone.
- Halofuginone or its derivatives may be a promising candidate for a therapy against T cells.

Inactivation of T cells is a widely used strategy for immunosuppression. Halofuginone (HF) is an antiprotozoal agent for treating parasites in veterinary medicine, and has been demonstrated to inhibit collagen type 1 synthesis, T helper 17 cell differentiation and cytokine production in activated T cells. The present study was designed to examine the biological effects of HF against T cell receptor and interleukin (IL)-2 stimulated T cell proliferation. T cell proliferation in cultured murine splenocytes was determined by methylthiazol tetrazolium assay. Cell apoptosis was mainly determined by fluorescence-activated cell sorting with Annexin-V and 7-aminoactinomycin D staining. Here, we showed that HF significantly suppressed T cell proliferation in naïve splenocyte cultures in response to alloantigen or anti-CD3 antibody (IC50, 2-2.5 nM; P < 0.0001), or in activated T cell cultures in response to IL-2 (IC50, 16 nM; P < 0.0001) in a dose-dependent manner. HF did neither attenuate IL-2 production in anti-CD3 antibody activated T cells nor disrupt STAT5 signaling in IL-2-stimulated T cells, but its anti-T cell proliferation was correlated with an increase in cell apoptosis and a decrease in proline uptake in culture medium. Further experiments showed that proline supplement in cell culture medium significantly prevented HF-mediated suppression of T cell proliferation and cell apoptosis. In conclusion, these data suggest that HF interferes with proline incorporation or uptake, resulting in apoptosis via amino acid starvation response in T cells in the response to antigen/mitogen or IL-2 stimulation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 16, Issue 4, August 2013, Pages 414-423
نویسندگان
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