Circular RNA 406961 interacts with ILF2 to regulate PM2.5-induced inflammatory responses in human bronchial epithelial cells via activation of STAT3/JNK pathways
Circular RNA 406961 interacts with ILF2 to regulate PM2.5-induced inflammatory responses in human bronchial epithelial cells via activation of STAT3/JNK pathways
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DOI：
10.1016/j.envint.2020.105755
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发表时间：
2020-08-01
影响因子：
11.8
通讯作者：
Jiang, Yiguo
中科院分区：
文献类型：
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作者：
Jia, Yangyang;Li, Xin;Jiang, Yiguo
细颗粒物（PM2.5）已被证实会增加肺炎、哮喘、肺纤维化和其他肺部疾病的发病率。气道炎症是呼吸系统的病理基础，了解气道炎症的分子机制可能有助于呼吸系统疾病的诊断和治疗。在我们的研究中，人支气管上皮细胞（BEAS-2B）暴露于不同浓度的PM2.5 48 h。PM2.5进入细胞，导致白细胞介素6（IL-6）和白细胞介素8（IL-8）的产生增加，环状RNA 406961（circ_406961）的表达减少。此外，以浓度为75 μ g/mL的PM2.5为研究对象进行了机理研究。功能实验进一步证实，circ_406961抑制PM2.5诱导的BEAS-2B细胞炎症。RNA pull-down和质谱分析表明，circ_406961与白细胞介素增强子结合因子2（IL F2）相互作用，IL F2可以调节信号转导和转录激活因子3（STAT 3）和丝裂原活化蛋白激酶8（MAPK 8，JNK）的磷酸化。我们的研究表明，circ_406961通过与ILF 2蛋白相互作用抑制STAT 3/JNK通路的激活，从而抑制PM2.5诱导的炎症反应。
Fine particulate matter (PM2.5) has been verified to augmented the incidence of pneumonia, asthma, pulmonary fibrosis, and other pulmonary diseases. Airway inflammation is the pathological basis of the respiratory system, and understanding the molecular mechanisms responsible for airway inflammation may thus support the diagnosis and treatment of respiratory diseases. In our study, human bronchial epithelial cells (BEAS-2B) were exposed to various concentrations of PM2.5 for 48 h. PM2.5 entered the cells, resulting in increased production of interleukin 6 (IL-6) and interleukin 8 (IL-8) and decreased the expression of circular RNA 406961 (circ_406961). Further, PM2.5 with a concentration of 75 mu g/mL was applied to mechanism study. Functional experiments further confirmed that circ_406961 inhibited PM2.5-induced BEAS-2B cell inflammation. RNA pull -down and mass spectrometry showed that circ_406961 interacted with interleukin enhancer -binding factor 2 (ILF2), which could regulate phosphorylation of signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase 8 (MAPK8, JNK). Our studies showed that circ_406961 inhibited activation of STAT3/JNK pathways via interacting with ILF2 protein, thereby inhibiting the PM2.5-induced inflammatory reaction.