细颗粒物致人肺泡上皮细胞炎性反应关键组分及机制探究OACSTPCD
Exploration of critical components for PM2.5 induced inflammatory reaction in human alveolar epithelial cells
目的:研究细颗粒物(PM2.5)不同组分对人Ⅱ型肺泡上皮细胞(A549)增殖的作用及机制.方法:制备PM2.5全颗粒、脂溶性和水溶性组分,观察PM2.5不同组分对A549形态的影响;MTT法评价PM2.5不同组分对细胞增殖的影响;酶联免疫吸附实验(ELISA)检测PM2.5不同组分对炎性因子表达的影响.在PM2.5组分暴露的基础上,给予丝裂原活化蛋白激酶(MAPK)信号通路抑制剂和地塞米松,分别检测A549增殖和炎性因子变化情况,MAPK信号通路相关蛋白的表达.结果:除PM2.5水溶性组分外,PM2.5全颗粒和脂溶性组分均能抑制A549细胞增殖,呈时间和浓度依赖性,染毒24 h后二者作用的IC50分别为199.9和142.1 μg/ml;二者可显著增加细胞上清液中炎性因子的表达.MAPK信号通路抑制剂(U0126、SB203580、SP600125)和地塞米松可显著增强WPPM2.5和LSPM2.5对A549细胞的抑制作用,抑制WPPM2.5和LSPM2.5致炎性因子表达的增加,促进JNK和ERK1/2的磷酸化.结论:PM2.5对A549细胞活力及炎症的影响主要与其非水溶性组分有关,其机制可能与激活ERK1/2 MAPK和JNK MAPK信号通路有关.
Objective:To observe the effect and mechanism of different components of fine particulate matter(PM2.5)on the proliferation of human type Ⅱ alveolar epithelial cells(A549).Methods:The whole particles,liposolu-ble-soluble and water-soluble of PM2.5 were prepared,and the effects of different components of PM2.5 on the mor-phology of A549 were observed.MTT assay was used to evaluate the effect of different components of PM2.5 on cell proliferation.ELISA was used to detect the effect of different components of PM2.5 on the expression of inflammatory factors.On the basis of PM25 component exposure,MAPK signaling pathway inhibitor and dexamethasone were giv-en to A549,and the changes in proliferation,inflammatory factors and the expression of MAPK signaling pathway re-lated proteins were detected.Results:The whole particles and liposoluble-soluble of PM2 5(WPPM2.5 and LSPM2 5)can inhibit the proliferation of A549 cells in a time-and concentration-dependent manner and the IC50 were 199.9,142.1 μg/ml,respectively.The inflammatory factors in cell culture supernatants increased significantly after WPPM2.5 and LSPM2.5 exposure.MAPK signaling pathway inhibitors(U0126,SB203580,SP600125)and dexametha-sone significantly enhanced the inhibitory effect of WPPM2.5 and LSPM2.5 on A549 cells,inhibited the increase in the expression of inflammatory factors induced by WPPM2 5 and LSPM2.5,and promoted the phosphorylation of JNK and ERK1/2.Conclusion:The effect of PM2.5on A549 cell viability and inflammation was related with water-insoluble components,and the mechanism may be related to the activation of ERK1/2 MAPK and JNK MAPK signaling path-ways.
王荣;张邱栋;张懿烨;贺红梅;王娜娜;秦蓓
西安医学院药学院,陕西西安 710021||西安市多靶协同抗高血压创新药物研制重点实验室,陕西西安 710021西安医学院医学技术学院,陕西西安 710021
基础医学
PM2.5A549细胞细胞毒性炎症反应丝裂原活化蛋白激酶信号通路关键组分
PM2.5Critical componentsA549 cellsCytotoxicityInflammatory responseMAPK signaling pathway
《陕西医学杂志》 2024 (001)
大气细颗粒物通过Shp2/MAPK炎性信号通路诱导气道高反应性的作用和机制
8-12 / 5
国家自然科学基金资助项目(81903288);西安医学院校级科技创新团队建设项目(2021TD03);国家级、省级、校级大学生创新创业训练计划项目(202311840020,121522107,121523020);西安医学院科研能力提升计划项目(2022NLTS070)
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