期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 34, 期 4, 页码 1359-1372出版社
KARGER
DOI: 10.1159/000366343
关键词
Acacetin; Kv1.3 potassium channel; Chemical blockade; Immunomodulatory; Human T cells
资金
- National Nature Science Foundation of China [81170164]
- Open Foundation of Hubei Key Laboratory of Biological Targeted Therapy [2013-81]
- National Basic Research Program of China (973 Program) [2013CB531103]
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 K-Ca currents in human T cells; Western blot was used to detect Kv1.3 expression as well as NFAT1 and NF-kappa B activity; Fluo-4, CCK-8 and an ELISA kit were used to measure Ca2+ 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 mu mol/L, respectively. Treatment with Acacetin for 24 h significantly inhibited Kv1.3 protein expression. Additionally, paralleling Kv1.3 inhibition, Acacetin also inhibited Ca2+ influx, the Ca2+-activated transcription factors NFAT1, NF-kappa B 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. Copyright (C) 2014 S. Karger AG, Basel
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