Acacetin blocks kv1.3 channels and inhibits human T cell activation.
Cell Physiol Biochem
; 34(4): 1359-72, 2014.
Article
en En
| MEDLINE
| ID: mdl-25301362
ABSTRACT
BACKGROUNDS/AIMS:
Acacetin, a natural flavonoid compound, has been proven to exert anti-inflammatory and immunomodulatory effects. Kv1.3 channels, highly expressed in human T cells, are attractive therapeutic targets to treat inflammatory and immunological disorders. The present study was designed to characterize the inhibition of Kv1.3 channels by Acacetin in human T cells and examine its role in T cell activation.METHODS:
Whole-cell patch-clamp was applied to record the Kv1.3 and KCa currents in human T cells; Western blot was used to detect Kv1.3 expression as well as NFAT1 and NF-κB activity; Fluo-4, CCK-8 and an ELISA kit were used to measure Ca(2+) influx, proliferation, and IL-2 secretion, respectively.RESULTS:
Acacetin decreased the Kv1.3 current, accelerated the decay rate and negatively shifted the steady-state inactivation curves in a concentration-dependent manner. The IC50 values at +40 mV for peak and the current at end of pulse were 21.09 ± 2.75 and 3.63 ± 0.25 µmol/L, respectively. Treatment with Acacetin for 24 h significantly inhibited Kv1.3 protein expression. Additionally, paralleling Kv1.3 inhibition, Acacetin also inhibited Ca(2+) influx, the Ca(2+)-activated transcription factors NFAT1, NF-κB p65/p50 activity, and proliferation as well as IL-2 production. Small interfering RNA against Kv1.3 reduced the inhibitory effect of Acacetin on IL-2 secretion.CONCLUSIONS:
Acacetin blocks the Kv1.3 channel and inhibits human T cell activation. This action most likely contributes to its immunomodulatory and anti-inflammatory actions.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
/
Linfocitos T
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Bloqueadores de los Canales de Potasio
/
Flavonas
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Canal de Potasio Kv1.3
Límite:
Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article