Licochalcones suppress degranulation by decreasing the intracellular Ca2+ level and tyrosine phosphorylation of ERK in RBL-2H3 cells.
Licochalcones suppress degranulation by decreasing the intracellular Ca2+ level and tyrosine phosphorylation of ERK in RBL-2H3 cells.
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DOI：
10.1016/j.intimp.2010.04.007
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发表时间：
2010-07
影响因子：
5.6
通讯作者：
Shota Tanifuji;E. Aizu-Yokota;M. Funakoshi-Tago;Y. Sonoda;H. Inoue;T. Kasahara
中科院分区：
文献类型：
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作者：
Shota Tanifuji;E. Aizu-Yokota;M. Funakoshi-Tago;Y. Sonoda;H. Inoue;T. Kasahara
肥大细胞通过释放多种介质，如组胺、5-羟色胺、白三烯和细胞因子，在变态反应性炎症中发挥关键作用。由抗原刺激激活的一系列事件的信号级联有助于调节肥大细胞脱颗粒。虽然已经开发了各种抗炎和抗过敏药物来抑制肥大细胞的脱颗粒，但其抑制机制尚不清楚。利可酮A是从新疆甘草根中分离得到的一种后查尔酮类化合物，具有抗炎等多种生物活性。我们研究了利科A和相关查尔酮对大鼠嗜碱性白血病细胞系RBL-2H3脱颗粒的影响。LICO A和LICO C(LICO C)对RBL-2H3细胞脱颗粒有明显的抑制作用，而LICO D(LICO D)对RBL-2H3细胞脱颗粒有明显的抑制作用。此外，LICO D还显著抑制细胞外信号调节激酶(ERK)和MEK的钙内流和磷酸化。这些结果表明，LICO D通过抑制细胞外钙内流和激活MEK-ERK通路来抑制肥大细胞脱颗粒。
Mast cells play a key role in allergic inflammation by releasing various mediators, such as histamine, serotonin, leukotrienes and cytokines. A signaling cascade of events activated by stimulation with antigens contributes to the regulation of mast cell degranulation. While various anti-inflammatory and anti-allergic drugs have been developed that inhibit degranulation of mast cells, the inhibitory mechanism has been poorly understood. Licochalcone A (Lico A) is a retrochalcone isolated from the root of Xinjiang liquorice and has been reported to exhibit various biological activities such as anti-inflammatory activity. We examined the effects of Lico A and related chalcones on degranulation in a rat basophilic leukemia cell line, RBL-2H3. Whereas Lico A and licochalcone C (Lico C) exhibited inhibitory activity with cytotoxicity, licochalcone D (Lico D) significantly inhibited the degranulation in RBL-2H3 cells with low cytotoxicity. Moreover, Lico D significantly inhibited the Ca2+influx and phosphorylation of extracellular signal regulated kinase (ERK) and MEK. These results suggest that Lico D inhibits mast cell degranulation via the inhibition of both extracellular Ca2+influx and activation of the MEK-ERK pathway.