Loureirin B, an essential component of Sanguis Draxonis, inhibits Kv1.3 channel and suppresses cytokine release from Jurkat T cells.
Sanguis draxonis (SD), also known as "Dragon's Blood", is a traditional herb medicine that has been used to treat a variety of complications with unknown mechanisms. Recent studies show that SD displays immunosuppressive activities and improves symptoms of type I diabetes in animal models. However, the mechanisms underlying SD's immunosuppressive actions are not completely understood. The voltage-gated Kv1.3 channel plays a critical role in the pathogenesis of autoimmune diseases by regulating the functions of both T cells and B cells. Here we investigated the effect of SD and one of its active components loureirin B (LrB) on Kv1.3. Both SD and LrB inhibited Kv1.3-mediated currents, produced a membrane depolarization, and reduced Ca(2+) influx in Jurkat T cells. In addition, application of LrB inhibited phytohemagglutinin (PHA)-induced IL-2 release from activated Jurkat T cells. Furthermore, point mutations in the selective filter region significantly reduced the inhibitory effect of LrB on Kv1.3. The results of these experiments provide evidence that LrB is a channel blocker of Kv1.3 by interacting with amino acid residues in its selective filter region. Direct inhibition of Kv1.3 in T cells by SD and LrB might be the cellular and molecular basis of SD-mediated immunosuppression.
College of pharmacy, South-Central University for Nationalities, Wuhan, 430074 P R China ; Center for the Study of Itch, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110 USA.
Shijin
S
Yin
College of pharmacy, South-Central University for Nationalities, Wuhan, 430074 P R China.
Qinglan
Q
Hu
Center for the Study of Itch, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110 USA.
Jialie
J
Luo
College of pharmacy, South-Central University for Nationalities, Wuhan, 430074 P R China.
Yuxin
Y
Li
College of pharmacy, South-Central University for Nationalities, Wuhan, 430074 P R China.
Chunlan
C
Lu
College of pharmacy, South-Central University for Nationalities, Wuhan, 430074 P R China.
Xuan
X
Chen
Center for the Study of Itch, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110 USA.
Hongzhen
H
Hu
IL-2; Kv1.3 channels; Loureirin B; Sanguis draxonis