Apigenin, a dietary flavonoid, sensitizes human T cells for activation-induced cell death by inhibiting PKB/Akt and NF-kappaB activation pathway.
Immunol Lett
; 121(1): 74-83, 2008 Nov 16.
Article
em En
| MEDLINE
| ID: mdl-18812189
ABSTRACT
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-kappaB activation and suppressing NF-kappaB-regulated anti-apoptotic molecules, cFLIP, Bcl-x(L), Mcl-1, XIAP and IAP, but not Bcl-2. Apigenin suppressed NF-kappaB translocation to nucleus and inhibited IkappaBalpha 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-kappaB activation upon TCR stimulation, apigenin selectively inhibited PI3K-PKB/Akt, but not PKC-theta 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-kappaB activation, and especially cFLIP and COX-2 expression that are important for functioning and maintenance of immune cells in inflammation, autoimmunity and lymphoproliferation.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Linfócitos T CD4-Positivos
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NF-kappa B
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Apoptose
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Apigenina
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Proteínas Proto-Oncogênicas c-akt
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Proteínas Reguladoras de Apoptose
Limite:
Humans
Idioma:
En
Revista:
Immunol Lett
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos