Wogonin Suppresses IL-10 Production in B Cells via STAT3 and ERK Signaling Pathway
Wogonin Suppresses IL-10 Production in B Cells via STAT3 and ERK Signaling Pathway
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汉黄芩素通过 STAT3 和 ERK 信号通路抑制 B 细胞中 IL-10 的产生
DOI：
10.1155/2020/3032425
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发表时间：
2020-06-01
影响因子：
4.1
通讯作者：
Zhang, Qi
中科院分区：
文献类型：
--
作者：
Fan, Li;Qiu, Dongbo;Zhang, Qi
汉黄芩素（5,7 - 二羟基 - 8 - 甲氧基黄酮）是黄芩提取物的一种成分，已有文献记载其具有广泛的抗炎和抗肿瘤活性，包括抑制调节性T细胞、调节效应T细胞功能以及介导巨噬细胞免疫。然而，汉黄芩素对B细胞的潜在作用尚未完全明确。在此，我们的研究结果显示汉黄芩素抑制B细胞中白细胞介素 - 10（IL - 10）的分泌。当纯化的B细胞在体外被脂多糖（LPS）激活时，汉黄芩素显著降低了上清液中IL - 10的产生量。B细胞对葡聚糖硫酸钠（DSS）诱导的结肠炎的保护作用在接触汉黄芩素后减弱。此外，对脂多糖处理的B细胞施用汉黄芩素抑制了信号转导及转录激活因子3（STAT3）和细胞外调节蛋白激酶（ERK）的磷酸化，但不抑制蛋白激酶B（AKT）的磷酸化。有趣的是，在那些与IL - 10信号相关的转录因子中，汉黄芩素特异性地降低了缺氧诱导因子 - 1α（Hif - 1α）的信使核糖核酸（mRNA）和蛋白质水平。总体而言，我们的研究表明汉黄芩素通过抑制STAT3和ERK信号通路以及抑制转录因子Hif - 1α的mRNA和蛋白质水平，潜在地抑制B细胞中IL - 10的产生。这些结果为汉黄芩素在B细胞中提供了新的潜在分子靶点，并帮助我们进一步了解其作用机制，这可能会在未来潜在地改善其临床应用。
Wogonin (5,7-dihydroxy-8-methoxyflavone) is an ingredient of the extracts from Scutellaria baicalensis, which has documented a wide spectrum of anti-inflammatory and antitumor activities, including inhibiting regulatory T cells, regulating effector T cell functions, and mediating macrophage immunity. However, the potential effect of Wogonin on B cells has not been fully understood. Here, our results showed that Wogonin inhibited IL-10 secretion in B cells. When purified B cells were activated by lipopolysaccharide (LPS) in vitro, the amount of IL-10 production in supernatant was decreased by Wogonin significantly. The protective role of B cells on dextran sulfate sodium- (DSS-) induced colitis was alleviated after exposure to Wogonin. Furthermore, administration of Wogonin on LPS-treated B cells suppressed phosphorylation of STAT3 and ERK, but not AKT. Interestingly, among those IL-10 signaling-associated transcription factors, mRNA and protein levels of Hif-1α were specifically decreased by Wogonin. Overall, our study indicates that Wogonin suppresses potentially IL-10 production in B cells via inhibition of the STAT3 and ERK signaling pathway as well as inhibition of mRNA and protein levels of the transcription factor Hif-1α. These results provide novel and potential molecular targets of Wogonin in B cells and help us further understand its mechanism of action, which could potentially improve its clinical application in the future.