PRMT5 promotes inflammation of cigarette smoke extract-induced bronchial epithelial cells by up-regulation of CXCL10

Abstract

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 24h 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.