Histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits anti-inflammatory activities through induction of mitochondrial damage and apoptosis in activated lymphocytes.
Int Immunopharmacol
; 12(4): 580-7, 2012 Apr.
Article
en En
| MEDLINE
| ID: mdl-22369900
Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has been proven to be an anti-cancer agent. Its anti-inflammatory activities have recently been observed both in in vitro and in vivo models. Yet its action on lymphocytes and the underlying mechanism are still not well known. In this study, in order to evaluate the anti-inflammatory function of SAHA, we analyzed the effects of SAHA on the proliferation, activation, cytokines secretion, cell cycle distribution and apoptosis of murine lymphocytes activated with concanavalin A (Con A). Our results demonstrated that SAHA inhibited the proliferation of Con A-activated lymphocytes in a dose-dependent manner. The expression of CD69 on CD3(+) T lymphocytes was significantly inhibited by SAHA. Intracellular cytokine staining analysis showed that SAHA could downregulate the expression of pro-inflammatory cytokines TNF-α, IL-6 and IFN-γ in T lymphocytes. Furthermore, analysis of sub-G(0)/G(1) peaks and annexin V binding populations revealed that SAHA induced apoptotic cell death in Con A-activated lymphocytes. Consistent with these results, SAHA treatment also induced a decrease of mitochondrial membrane potential and cleavage of caspase-3 and PARP in these cells. Moreover, SAHA caused an accumulation of phosphorylated histone H2A.X, indicating increased double strand DNA breaks. These findings suggest that induction of apoptosis through the mitochondrial pathway may contribute to the anti-inflammatory activities of SAHA on activated lymphocytes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos
/
Inhibidores de Histona Desacetilasas
/
Ácidos Hidroxámicos
/
Antiinflamatorios
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2012
Tipo del documento:
Article
Pais de publicación:
Países Bajos