1,6-O,O-Diacetylbritannilactone Inhibits Eotaxin-1 and ALOX15 Expression Through Inactivation of STAT6 in A549 Cells
1,6-O,O-Diacetylbritannilactone Inhibits Eotaxin-1 and ALOX15 Expression Through Inactivation of STAT6 in A549 Cells
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1,6-O,O-Di乙酰britannilactone 通过灭活 A549 细胞中的 STAT6 来抑制 Eotaxin-1 和 ALOX15 表达。
DOI：
10.1007/s10753-017-0637-y
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发表时间：
2017-12-01
期刊：
影响因子：
5.1
通讯作者：
Jin, Meihua
中科院分区：
文献类型：
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作者：
Chen, Xi;Ji, Ning;Jin, Meihua
1,6-O,O-二乙酰基布里坦尼内酯 (OODBL) 是一种植物倍半萜内酯，此前曾报道显示出多种药理作用，例如抗癌和抗炎活性。在本研究中，我们研究了 OODBL 对人肺 A549 细胞中白介素 (IL)-4 诱导的信号转导子和转录激活子 6 (STAT6) 信号通路的抗炎作用。我们发现 OODBL 以剂量依赖性方式显着抑制 IL-4 诱导的eotaxin-1 和花生四烯酸 15-脂氧合酶-1 (ALOX15) 的信使 RNA (mRNA) 表达。为了阐明 OODBL 的作用机制，我们检查了 OODBL 对 STAT6 激活的影响。 OODBL 降低了 STAT6 磷酸化和报告基因活性。此外，OODBL 抑制 Janus 激酶 3 (JAK3) 的磷酸化，而不影响 JAK1。总而言之，OODBL 通过抑制 STAT6 和 JAK3 的激活来消除 IL-4 诱导的eotaxin-1 和 ALOX15 mRNA 表达。这些结果表明，OODBL 作为先导化合物对炎症性疾病尤其是过敏性气道疾病具有潜在的治疗功效。
1,6-O,O-Diacetylbritannilactone (OODBL), a plant sesquiterpene lactone, was previously reported to show multiple pharmacological effects such as anti-cancer and anti-inflammatory activities. In this study, we investigated the anti-inflammatory effect of OODBL on interleukin (IL)-4-induced signal transducer and activator of transcription 6 (STAT6) signaling pathway in human lung A549 cells. We found that OODBL dramatically inhibited IL-4-induced messenger RNA (mRNA) expression of eotaxin-1 and arachidonate 15-lipoxygenase-1 (ALOX15) in a dose-dependent manner. To clarify the action mechanism of OODBL, we examined the effect of OODBL on activation of STAT6. OODBL decreased both STAT6 phosphorylation and reporter gene activity. Furthermore, OODBL suppressed phosphorylation of Janus Kinase 3 (JAK3) without affecting JAK1. Taken together, OODBL abolished IL-4-induced eotaxin-1 and ALOX15 mRNA expressions by repressing the activation of STAT6 and JAK3. These results suggest that OODBL has a potential therapeutic efficacy on inflammatory diseases especially allergic airway disease as a lead compound.