Qing Hua Chang Yin inhibits the LPS-induced activation of the IL-6/STAT3 signaling pathway in human intestinal Caco-2 cells
Qing Hua Chang Yin inhibits the LPS-induced activation of the IL-6/STAT3 signaling pathway in human intestinal Caco-2 cells
复制标题
清花常饮抑制LPS诱导的人肠Caco-2细胞IL-6/STAT3信号通路的激活
DOI：
10.3892/ijmm.2015.2083
复制
发表时间：
2015-04-01
影响因子：
5.4
通讯作者：
Sferra, Thomas J.
中科院分区：
文献类型：
--
作者：
Ke, Xiao;Hu, Guanghong;Sferra, Thomas J.
越来越多的证据表明，溃疡性结肠炎（UC）的发病机制受到白细胞介素-6（IL-6）/信号转导和转录激活因子3（STAT 3）通路及其负反馈调节因子细胞因子信号转导抑制因子3（SOCS 3）的高度调节。因此，调节IL-6/STAT 3/SOCS 3的信号反馈回路可能被证明是治疗UC的新的治疗方法。清化肠饮是临床上用于治疗溃疡性结肠炎的传统中药制剂。我们以前曾报道过QHCY通过抑制核因子-κ B（NF-κ B）通路在体内和体外改善急性肠道炎症。为了进一步阐明QHCY的抗炎作用机制，本研究采用脂多糖（LPS）刺激人肠Caco-2细胞，建立人肠上皮细胞炎症模型，观察QHCY对炎症Caco-2细胞IL-6/STAT 3/SOCS 3信号网络的影响。通过ELISA测量IL-6的水平，并且通过蛋白质印迹分析测量STAT 3和SOCS 3的水平。我们发现QHCY以剂量依赖性方式显著抑制LPS诱导的Caco-2细胞分泌促炎性IL-6。此外，QHCY深刻抑制LPS诱导的Janus激活激酶1（JAK 1），JAK 2和STAT 3的磷酸化。此外，用QHCY处理显著增加SOCS 3的表达。总之，本研究的结果表明，IL-6/STAT 3/SOCS 3信号网络的调节可能是QHCY发挥其抗炎作用的机制之一。
Increasing evidence indicates that the pathogenesis of ulcerative colitis (UC) is highly regulated by the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway and its negative feedback regulator, suppressor of cytokine signaling 3 (SOCS3). Therefore, modulating the signaling feedback loop of IL-6/STAT3/SOCS3 may prove to be a novel therapeutic approach for the treatment of UC. Qing Hua Chang Yin (QHCY) is a traditional Chinese formulation that has long been used in clinic for the treatment of UC. We have previously reported that QHCY ameliorates acute intestinal inflammation in vivo and in vitro through the suppression of the nuclear factor-kappa B (NF-kappa B) pathway. In the present study, in order to further elucidate the mechanisms responsible for the anti-inflammatory activities of QHCY, we stimulated human intestinal Caco-2 cells with lipopolysaccharide (LPS) to create an in vitro model of an inflamed human intestinal epithelium, and evaluated the effects of QHCY on the IL-6/STAT3/SOCS3 signaling network in inflamed Caco-2 cells. The levels of IL-6 were measured by ELISA and the levels of STAT3 and SOCS3 were measured by western blot analysis. We found that QHCY significantly inhibited the LPS-induced secretion of pro-inflammatory IL-6 in the Caco-2 cells in a dose-dependent manner. Moreover, QHCY profoundly suppressed the LPS-induced phosphorylation of Janus-activated kinase 1 (JAK1), JAK2 and STAT3. Furthermore, treatment with QHCY markedly augmented the expression of SOCS3. Taken together, the findings of the present study suggest that the modulation of the IL-6/STAT3/SOCS3 signaling network may be one of the mechanisms through which QHCY exerts its anti-inflammatory effects.