BACKGROUND Chronic obstructive pulmonary disease (COPD) is related to inflammation and obstruction of the lungs and airways. Protein arginine methyltransferase 5 (PRMT5) that promotes arginine methylation of histones is associated with inflammation of endothelial cell and is implicated in lung branching morphogenesis and progression of lung cancer. The mechanism of PRMT5 in inflammatory response of COPD was explored in this study. METHODS Human bronchial epithelial cells, 16HBE, were treated with cigarette smoke extract for 24 h to establish cell model of COPD. Cell viability was examined by MTT assay. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays were used to explore expression of PRMT5. Expression of Interleukin (IL)-6, IL-8, tumor necrosis factor-α (TNF-α), and IL-1β were investigated by enzyme-linked-ithe mmunosorbent serologic assay. RESULTS Cigarette smoke extract treatment induced cytotoxity of 16HBE with reduced cell viability. PRMT5 was enhanced in cigarette smoke extract-induced 16HBE. Knockdown of PRMT5 increased cell viability of cigarette smoke extract-induced 16HBE, and attenuated cigarette smoke extract-induced increase of IL-6, IL-8, TNF-α, and IL-1β. Up-regulation of C-X-C Motif Chemokine 10 (CXCL10) in cigarette smoke extract-induced 16HBE was restored by knockdown of PRMT5. Over-expression of CXCL10 counteracted with the suppressive effect of PRMT5 silence on expression of IL-6, IL-8, TNF-α, and IL-1β. Moreover, PRMT5 silence-induced increase of cell viability in cigarette smoke extract-induced 16HBE was reversed by over-expression of CXCL10. CONCLUSION Knockdown of PRMT5 promoted cell viability of cigarette smoke extract-induced 16HBE, and reduced inflammation through down-regulation of CXCL10.

中文翻译：

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PRMT5 通过上调 CXCL10 促进香烟烟雾提取物诱导的支气管上皮细胞的炎症。

背景技术慢性阻塞性肺病(COPD)与肺部和气道的炎症和阻塞有关。促进组蛋白精氨酸甲基化的蛋白质精氨酸甲基转移酶 5 (PRMT5) 与内皮细胞的炎症相关，并与肺癌的肺分支形态发生和进展有关。本研究探讨PRMT5在COPD炎症反应中的作用机制。方法用香烟烟雾提取物处理人支气管上皮细胞16HBE 24 h建立COPD细胞模型。通过MTT测定检查细胞活力。使用蛋白质印迹和逆转录定量聚合酶链反应 (RT-qPCR) 测定来探索 PRMT5 的表达。白细胞介素（IL）-6、IL-8、肿瘤坏死因子-α（TNF-α）的表达，通过酶联免疫吸附血清学测定研究了IL-1β和IL-1β。结果 香烟烟雾提取物处理诱导 16HBE 的细胞毒性，降低细胞活力。PRMT5 在香烟烟雾提取物诱导的 16HBE 中增强。PRMT5 的敲低增加了香烟烟雾提取物诱导的 16HBE 的细胞活力，并减弱了香烟烟雾提取物诱导的 IL-6、IL-8、TNF-α 和 IL-1β 的增加。通过 PRMT5 的敲低恢复了香烟烟雾提取物诱导的 16HBE 中 CXC 基序趋化因子 10 (CXCL10) 的上调。CXCL10 的过表达抵消了 PRMT5 沉默对 IL-6、IL-8、TNF-α 和 IL-1β 表达的抑制作用。此外，在香烟烟雾提取物诱导的 16HBE 中，PRMT5 沉默诱导的细胞活力增加被 CXCL10 的过表达逆转。