کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3356070 | 1217234 | 2008 | 10 صفحه PDF | دانلود رایگان |
Resistance of T cells to activation-induced cell death (AICD) is associated with autoimmunity and lymphoproliferation. We found that apigenin (4′,5,7-trihydroxyflavone), a non-mutagenic dietary flavonoid, augmented both extrinsic and intrinsic pathways of apoptosis in recurrently activated, but not in primarily stimulated, human blood CD4+ T cells. Apigenin potentiated AICD by inhibiting NF-κB activation and suppressing NF-κB-regulated anti-apoptotic molecules, cFLIP, Bcl-xL, Mcl-1, XIAP and IAP, but not Bcl-2. Apigenin suppressed NF-κB translocation to nucleus and inhibited IκBα phosphorylation and degradation in response to TCR stimulation in reactivated peripheral blood CD4 T cells, as well as in leukemic Jurkat T cell lines. Among the pathways that lead to NF-κB activation upon TCR stimulation, apigenin selectively inhibited PI3K-PKB/Akt, but not PKC-θ activation in the human T cells, and synergized with a PI3K inhibitor to markedly augment AICD. Apigenin also suppressed expression of anti-apoptotic cyclooxygenase 2 (COX-2) protein in activated human T cells, but it did not affect activation of Erk MAPKinase. Thus, in chronically activated human T cells, relatively non-toxic apigenin can suppress anti-apoptotic pathways involving NF-κB activation, and especially cFLIP and COX-2 expression that are important for functioning and maintenance of immune cells in inflammation, autoimmunity and lymphoproliferation.
Journal: Immunology Letters - Volume 121, Issue 1, 16 November 2008, Pages 74–83