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环境细颗粒物相关自噬减轻柏花粉蛋白 3(Pla3)诱导的肺部炎症。

Ambient particulate matter-associated autophagy alleviates pulmonary inflammation induced by Platanus pollen protein 3 (Pla3).

机构信息

School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China; Lab of Plant Cell Biology, Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai 200444, China.

School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.

出版信息

Sci Total Environ. 2021 Mar 1;758:143696. doi: 10.1016/j.scitotenv.2020.143696. Epub 2020 Dec 10.

Abstract

Subpollen particles (SPPs) with diameter less than 1 mm released from allergenic pollen grains contain allergens could trigger asthma and lung inflammation after being inhaled. In the meaning time, ambient fine particles attached on the pollen grains could have further effects on the inflammation. However, the mechanisms underlying these phenomena have not been fully elucidated. In this study, the effects of autophagy triggered by PM and Platanus SPPs were evaluated by using the A549 cell lines and a pollen sensitized rat model. First, autophagy in A549 cells was analyzed after exposure to PM using acridine orange staining, real-time quantitative PCR (qRT-PCR), and western blot (WB) assays. The increased levels of ROS, superoxide dismutase, and malonaldehyde in the lung homogenates of rats exposed to SPPs indicated that inflammatory response was triggered in the lungs. Treatment with autophagy-inhibiting drugs showed that autophagy suppressed ROS formation and decreased the production of thymic stromal lymphopoietin (TSLP), a critical pathway altering the inflammatory response. Although the effect was indirect, autophagy appeared to negatively regulate TSLP levels, resulting in a compromised immune response. These results suggested that SPPs promote ROS generation and increase TSLP levels, triggering downstream inflammation reactions. However, ambient PM could aggravate autophagy, which in turn effectively suppressed ROS and TSLP levels, leading to the alleviation of the immune response and pulmonary inflammation.

摘要

粒径小于 1mm 的花粉衍生的亚花粉颗粒(SPPs)中含有过敏原,被吸入后可引发哮喘和肺部炎症。与此同时,环境中的细颗粒物附着在花粉颗粒上可能会对炎症产生进一步的影响。然而,这些现象背后的机制尚未完全阐明。在这项研究中,通过使用 A549 细胞系和花粉致敏大鼠模型,评估了 PM 和悬铃木 SPPs 引发的自噬作用。首先,通过吖啶橙染色、实时定量 PCR(qRT-PCR)和 Western blot(WB)实验分析了 A549 细胞暴露于 PM 后自噬的情况。暴露于 SPPs 的大鼠肺匀浆中 ROS、超氧化物歧化酶和丙二醛水平的升高表明肺部发生了炎症反应。用自噬抑制药物处理表明,自噬抑制了 ROS 的形成,并减少了胸腺基质淋巴细胞生成素(TSLP)的产生,这是改变炎症反应的关键途径。尽管这种作用是间接的,但自噬似乎会负调控 TSLP 水平,从而削弱免疫反应。这些结果表明,SPPs 促进 ROS 的产生并增加 TSLP 水平,引发下游炎症反应。然而,环境 PM 可能会加重自噬,进而有效抑制 ROS 和 TSLP 水平,减轻免疫反应和肺部炎症。

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