Fine Particulate Matter (PM2.5) upregulates expression of Inflammasome NLRP1 via ROS/NF-κB signaling in HaCaT Cells
Fine Particulate Matter (PM2.5) upregulates expression of Inflammasome NLRP1 via ROS/NF-κB signaling in HaCaT Cells
复制标题
细颗粒物 (PM) 通过 HaCaT 细胞中的 ROS/NF-κB 信号传导上调炎症小体 NLRP1 的表达。
DOI：
10.7150/ijms.46962
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发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Xu, Feng
中科院分区：
文献类型：
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作者：
Dong, Liu;Hu, Ruiming;Xu, Feng
皮肤作为人体的主要器官，持续暴露于PM2.5刺激下，这可能对皮肤的生理产生特定的毒性影响。本研究旨在研究PM2.5对皮肤细胞炎症小体形成的影响，探讨PM2.5与皮肤炎症的可能机制。采用实时荧光定量PCR和蛋白质印迹法检测不同浓度PM2. 5作用24 h后，人永生化表皮细胞（HaCaT）中炎性小体相关基因mRNA和蛋白水平的变化。PM2.5暴露后NLRP 1的表达在mRNA和蛋白水平上均显著增加，而ELISA检测到细胞培养物中IL-1 β的分泌蛋白水平升高，这是NLRP 1的主要下游因子之一。另外，NF-κ B抑制剂可逆转NLRP 1和IL-1 β的上调，提示PM2.5可能通过激活NF-κ B通路促进NLRP 1的表达。此外，在PM2.5处理的细胞中也发现了高水平的ROS，并且ROS的抑制也可以逆转PM2.5刺激的NK-κ B的产生，这意味着ROS参与了这种皮肤炎症过程。
Skin, as the major organ of a human body, is constantly exposed to PM2.5 stimulation, which may exert specific toxic influences on the physiology of skin. This study aims to investigate the effect of PM2.5 on the formation of inflammasomes in skin cells and to explore the potential mechanism linking PM2.5 and skin inflammation. Changes in mRNA and protein levels of inflammasome-related genes were detected by real-time PCR and western blot in human immortalized epidermal cells (HaCaT) treated with PM2.5 at multiple concentrations for 24 hours. The expression of NLRP1 was increased significantly both in mRNA and protein levels after PM2.5 exposure while the elevated secretory protein level of IL-1 beta in cell culture was detected by ELISA, which is one of the main downstream factors of NLRP1. In addition, the upregulation of NLRP1 and IL-1 beta could be reversed by NF-kappa B inhibitor indicating that PM2.5 may promote NLRP1 expression through activating NF-kappa B pathway. Furthermore, high ROS level was also found in cells treated with PM2.5 and inhibition of ROS could also reverse NK-kappa B production stimulated by PM2.5 that means ROS is involved in this skin inflammation process.