{"title":"Environmental pollutant 3-methyl-4-nitrophenol promotes the expression of oncostatin M to exacerbate airway allergic inflammation.","authors":"Lihua Mo, Xinxin Wang, Yun Liao, Yu Liu, Aifa Tang, Jing Li, Pingchang Yang","doi":"10.1093/cei/uxae078","DOIUrl":null,"url":null,"abstract":"<p><p>Asthma exacerbation is a common clinical occurrence. The causal factors are not fully understood yet. Environmental pollution is linked to asthma exacerbation. The objective of this study is to elucidate the role of 3-methyl-4-nitrophenol (MNP), an environmental pollutant, in asthma exacerbation. In this study, an airway allergy mouse model was established with ovalbumin as a specific antigen with or without the presence of MNP. The results showed that, in a mouse model, the intensity of airway allergy was significantly increased by exposure to MNP. RNAseq results showed an increase in endoplasmic reticulum (ER) stress-associated molecules and the Osm expression in airway epithelial cells of mice with airway allergy. Exposure of epithelial cells to MNP in culture induced the expression of oncostatin M (OSM) and ER stress associated molecules. The OSM receptor was expressed by macrophages. OSM could drive macrophages to produce tumor necrosis factor-α (TNF-α). Inhibition of PERK, one of the key molecules of ER stress, or depletion of OSM receptor in macrophages, could effectively attenuate the MNP/ovalbumin protocol induced airway allergy. To sum up, by promoting ER stress, environmental pollutant MNP can cause airway epithelial cells to produce OSM. The latter induces macrophages to produce TNF-α, which can exacerbate airway allergy.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482495/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and experimental immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/cei/uxae078","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Asthma exacerbation is a common clinical occurrence. The causal factors are not fully understood yet. Environmental pollution is linked to asthma exacerbation. The objective of this study is to elucidate the role of 3-methyl-4-nitrophenol (MNP), an environmental pollutant, in asthma exacerbation. In this study, an airway allergy mouse model was established with ovalbumin as a specific antigen with or without the presence of MNP. The results showed that, in a mouse model, the intensity of airway allergy was significantly increased by exposure to MNP. RNAseq results showed an increase in endoplasmic reticulum (ER) stress-associated molecules and the Osm expression in airway epithelial cells of mice with airway allergy. Exposure of epithelial cells to MNP in culture induced the expression of oncostatin M (OSM) and ER stress associated molecules. The OSM receptor was expressed by macrophages. OSM could drive macrophages to produce tumor necrosis factor-α (TNF-α). Inhibition of PERK, one of the key molecules of ER stress, or depletion of OSM receptor in macrophages, could effectively attenuate the MNP/ovalbumin protocol induced airway allergy. To sum up, by promoting ER stress, environmental pollutant MNP can cause airway epithelial cells to produce OSM. The latter induces macrophages to produce TNF-α, which can exacerbate airway allergy.
环境污染物 3-甲基-4-硝基苯酚会促进 oncostatin M 的表达,从而加剧气道过敏性炎症。
哮喘加重是一种常见的临床现象。其致病因素尚不完全清楚。环境污染与哮喘恶化有关。本研究旨在阐明环境污染物 3-甲基-4-硝基苯酚(MNP)在哮喘恶化中的作用。本研究以卵清蛋白为特异性抗原,在有或没有 MNP 的情况下建立了气道过敏小鼠模型。结果显示,在小鼠模型中,暴露于 MNP 会显著增加气道过敏的强度。RNAseq 结果显示,气道过敏小鼠气道上皮细胞中的 ER 应激相关分子和 Osm 表达量增加。将上皮细胞暴露于 MNP 培养液中可诱导 OSM 和 ER 应激相关分子的表达。巨噬细胞表达 OSM 受体。OSM 可驱动巨噬细胞产生 TNF-α。抑制ER应激的关键分子之一PERK或消耗巨噬细胞中的OSM受体,可有效减轻MNP/OVA方案诱导的气道过敏。综上所述,环境污染物MNP可通过促进ER应激,促使气道上皮细胞产生OSM。后者诱导巨噬细胞产生 TNF-α,从而加剧气道过敏。
期刊介绍:
Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice.
The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.