Atorvastatin inhibits T cell activation through 3-hydroxy-3-methylglutaryl coenzyme A reductase without decreasing cholesterol synthesis.
J Immunol
; 179(6): 3613-21, 2007 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-17785796
ABSTRACT
The localization of the TCR and other signaling molecules in membrane rafts (MR) is essential for the activation of T lymphocytes. MR are stabilized by sphingolipids and cholesterol. Activation of T lymphocytes leads to the confluence of small MR and the formation of an immunological synapse that is essential for sustained activation and proliferation. In this study, we investigated the effect of statins on MR and T cell activation in superantigen-stimulated human PBMC. Atorvastatin significantly inhibited cellular activation and proliferation. The binding of cholera toxin B subunit to isolated MR and to whole cells was inhibited by low doses of statins. Statins reduce the association of critical signaling proteins such as Lck and linker of activation in T cells with MR in stimulated T cells. The expression of activation markers CD69 and CD25 was inhibited. Several statin-mediated mechanisms, such as a lower stimulation with MHC-II, an inhibition of costimulation by direct binding of statins to LFA-1, a reduced secretion of cytokines, or a depletion of cellular cholesterol pools, were excluded. Inhibition of protein prenylation had a similar effect on T cell proliferation, suggesting that a reduced protein prenylation might contribute to the statin-mediated inhibition of T cell activation. Statins induce both lower levels of low-density lipoprotein cholesterol and inhibition of T cell activation, which might contribute to an inhibition of atherosclerosis.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirroles
/
Activación de Linfocitos
/
Linfocitos T
/
Colesterol
/
Hidroximetilglutaril-CoA-Reductasas NADP-Dependientes
/
Ácidos Heptanoicos
/
Inmunosupresores
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Alemania