sincalide and acacetin

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.. 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.. 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.. Acacetin blocks the Kv1.3 channel and inhibits human T cell activation. This action most likely contributes to its immunomodulatory and anti-inflammatory actions.

Topics: Aniline Compounds; Anti-Inflammatory Agents; Calcium; Cell Line; Cell Line, Tumor; Cell Proliferation; Flavones; Humans; Interleukin-2; Jurkat Cells; Kv1.3 Potassium Channel; Lymphocyte Activation; Membrane Potentials; NF-kappa B; NFATC Transcription Factors; Potassium Channel Blockers; Sincalide; T-Lymphocytes; Xanthenes