Chlorogenic acid induces apoptosis to inhibit inflammatory proliferation of IL-6-induced fibroblast-like synoviocytes through modulating the activation of JAK/STAT and NF-κB signaling pathways
Chlorogenic acid induces apoptosis to inhibit inflammatory proliferation of IL-6-induced fibroblast-like synoviocytes through modulating the activation of JAK/STAT and NF-κB signaling pathways
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DOI：
10.3892/etm.2016.3136
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发表时间：
2016-05-01
影响因子：
2.7
通讯作者：
Chai, Limin
中科院分区：
文献类型：
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作者：
Lou, Lixia;Zhou, Jingwei;Chai, Limin
绿原酸（CGA）是金银花的主要成分，金银花是一种用于治疗类风湿性关节炎的中药。本研究旨在探讨CGA是否能够通过诱导凋亡来抑制成纤维细胞样滑膜细胞系（RSC-364）在白细胞介素(IL)-6刺激下的增殖。IL-6或IL-6加CGA孵育后，MTT法检测RSC-364细胞的增殖情况。流式细胞术检测凋亡细胞比例。Western blot分析janus活化激酶/信号传导和转录激活因子3 （JAK/STAT）信号通路[磷酸化(p)-STAT3， JAK1和gp130]和核因子kappa B （NF-kappa B）信号通路[磷酸化(p)- kappa B激酶亚基α / β和NF-kappa B p50抑制剂]关键分子的蛋白表达水平。结果表明，CGA可通过诱导凋亡抑制IL-6介导的RSC-364细胞的炎症增殖。CGA还能够抑制JAK/STAT和NF-kappa B信号通路关键分子的表达水平，并通过il -6介导的信号传导抑制这些信号通路在炎症反应中的激活，从而抑制滑膜细胞的炎症增殖。本研究结果表明，CGA可能通过诱导RA患者滑膜细胞凋亡来抑制滑膜炎症性增生。
Chlorogenic acid (CGA) is the primary constituent of Caulis Lonicerae, a Chinese herb used for the treatment of rheumatoid arthritis (RA). The present study aimed to investigate whether CGA was able to inhibit the proliferation of the fibroblast-like synoviocyte cell line (RSC-364), stimulated by interleukin (IL)-6, through inducing apoptosis. Following incubation with IL-6 or IL-6 and CGA, the cellular proliferation of RSC-364 cells was detected by MTT assay. The ratio of apoptosed cells were detected by flow cytometry. Western blot analysis was performed to observe protein expression levels of key molecules involved in the Janus-activated kinase/signal transducer and activator of transcription 3 (JAK/STAT) signaling pathway [phosphorylated (p)-STAT3, JAK1 and gp130] and the nuclear factor kappa B (NF-kappa B) signaling pathway [phosphorylated (p)-inhibitor of kappa B kinase subunit alpha/beta and NF-kappa B p50). It was revealed that CGA was able to inhibit the inflammatory proliferation of RSC-364 cells mediated by IL-6 through inducing apoptosis. CGA was also able to suppress the expression levels of key molecules in the JAK/STAT and NF-kappa B signaling pathways, and inhibit the activation of these signaling pathways in the inflammatory response through IL-6-mediated signaling, thereby resulting in the inhibition of the inflammatory proliferation of synoviocytes. The present results indicated that CGA may have potential as a novel therapeutic agent for inhibiting inflammatory hyperplasia of the synovium through inducing synoviocyte apoptosis in patients with RA.