Histone deacetylase inhibitors suppress natural killer cell cytolytic activity.
FEBS Lett
; 581(7): 1317-22, 2007 Apr 03.
Article
em En
| MEDLINE
| ID: mdl-17349632
ABSTRACT
Treatment of transformed cells from leukemia or solid tumors with histone deacetylase inhibitors (HDACi) was shown to increase their sensitivity to NK cell lysis. In this study, treatment of IL-2-activated NK cells with HDACi including suberoylanilide hydroxamic acid and valproic acid was studied. Both drugs at therapeutic concentrations inhibited NK cell cytotoxicity on human leukemic cells. This inhibition was associated with decreased expression and function of NK cell activating receptors NKp46 and NKp30 as well as impaired granule exocytosis. NFkappaB activation in IL-2-activated NK cells was inhibited by both HDACi. Pharmacologic inhibition of NFkappaB activity resulted in similar effects on NK cell activity like those observed for HDACi. These results demonstrate for the first time that HDACi prevent NK cytotoxicity by downregulation of NK cell activating receptors probably through the inhibition of NFkappaB activation.
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Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Receptores Imunológicos
/
Citotoxicidade Imunológica
/
Inibidores Enzimáticos
/
Inibidores de Histona Desacetilases
Limite:
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Alemanha