Wildland fires contribute significantly to the ambient air pollution burden worldwide, causing a range of adverse health effects in exposed populations. The toxicity of woodsmoke, a complex mixture of gases, volatile organic compounds, and particulate matter, is commonly studied in vitro using isolated exposures of conventionally cultured lung cells to either resuspended particulate matter or organic solvent extracts of smoke, leading to incomplete toxicity evaluations. This study aimed to improve our understanding of the effects of woodsmoke inhalation by building an advanced in vitro exposure system that emulates human exposure of the airway epithelium. We report the development and characterization of an innovative system that permits live-cell monitoring of the intracellular redox status of differentiated primary human bronchial epithelial cells cultured at an air-liquid interface (pHBEC-ALI) as they are exposed to unfractionated woodsmoke generated in a tube furnace in real time. pHBEC-ALI exposed to freshly generated woodsmoke showed oxidative changes that were dose-dependent and reversible, and not attributable to carbon monoxide exposure. These findings show the utility of this novel system for studying the molecular initiating events underlying woodsmoke-induced toxicity in a physiologically relevant in vitro model, and its potential to provide biological plausibility for risk assessment and public health measures.
Correction: Particle and Fibre Toxicology (2023) 20:45https://doi.org/10.1186/s12989-023-00555-5
Following publication of the original article [1], the authors reported some spelling and bibliograph errors. Below is a table of corrections which have been implemented in the original article.
The original article [1] has been corrected.
Section | Originally published text | Corrected text |
|---|---|---|
Abstract | Perinatal exposure to titanium dioxide (TiO2), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel disease (IBD) later in life | Perinatal exposure to titanium dioxide (TiO2), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel diseases (IBD) later in life |
Background | A significant number of human chronic diseases (inflammatory, metabolic …) is linked to a deficiency of the IBF and some of them, like IBD, exhibit alterations of the four IBF’s compartments [8, 9] | significant number of human chronic diseases (inflammatory, metabolic …) is linked to a deficiency of the IBF and some of them, like IBD, exhibit alterations of the three IBF’s compartments [8, 9] |
To evaluate this hypothesis, we exposed pregnant female C57BL/6 mice to 9 mg E171/kg b.w./day via their drinking water,from the beginning of gestation until 3 weeks postdelivery | To evaluate this hypothesis, we exposed pregnant female C57BL/6 mice to 9 mg E171/kg b.w./day via their drinking water, from the beginning of gestation until 4 weeks postdelivery | |
This exposure concentration is in the lower range of the estimated daily exposure of human adults, which ranges between 5.5 and 10.4 mg/kg b.w./day according to EFSA’s estimations [ref 35] | This exposure concentration is in the lower range of the estimated daily exposure of human adults, which ranges between 5.5 and 10.4 mg/kg b.w./day according to EFSA’s estimations [29] | |
When considering the guidances on dose conversion between human and animal exposure, such as the Nair and Jacob practice guide or FDA’s guidelines, we previously estimated that doses up to 50–60 mg/kg b.w./day in mice would be realistic [ref notre revue PFT] confirming that the dose used in the present study can be considered as a low exposure dose | When considering the guidances on dose conversion between human and animal exposure, such as the Nair and Jacob practice guide or FDA’s guidelines, we previously estimated that doses up to 50–60 mg/kg b.w./day in mice would be realistic [14] confirming that the dose used in the present study can be considered as a low exposure dose
更正：Particle and Fibre Toxicology (2023) 20:45https://doi.org/10.1186/s12989-023-00555-5Following 原文[1]发表后，作者报告了一些拼写和文献错误。以下是原文[1]的更正表。节最初发表的文本更正后的文本摘要作为食源性微粒的二氧化钛（TiO2）的产前暴露可能会影响肠道屏障功能和日后患炎症性肠病（IBD）的易感性作为食源性微粒的二氧化钛（TiO2）的产前暴露可能会影响肠道屏障功能和日后患炎症性肠病（IBD）的易感性背景大量人类慢性疾病（炎症性、代谢性......）与肠道屏障功能缺乏有关。为了评估这一假设，我们通过饮用水向怀孕的雌性 C57BL/6 小鼠暴露 9 mg E171/kg b. w./天。w./day via their drinking water,from the beginning of pregnancy until 3 weeks postdelivery.根据欧洲食品安全局（EFSA）的估计，这一暴露浓度处于人类成人每日暴露量的较低范围，即介于 5.5 至 10.4 毫克/千克体重/天之间[参考文献 35]。根据欧洲食品安全局的估计，这一暴露浓度处于人类成人每日暴露量估计值的较低范围，在 5.5 至 10.4 毫克/千克体重/天之间。当考虑到人类和动物暴露剂量换算指南（如 Nair 和 Jacob 实践指南或 FDA 指南）时，我们之前估计小鼠体内的剂量最高可达 50-60 mg/kg b. w. /day [ref notre revue PFT]，这证实本研究中使用的剂量可被视为低暴露剂量。结果图 1 食源性二氧化钛通过人体屏障转移的能力。A-G 野生型雌性小鼠暴露于二氧化钛（9 毫克/体重/天）图 1 食源性二氧化钛在人体屏障中的迁移能力。A-G 野生型雌性小鼠暴露于 TiO2（9 毫克/千克体重/天） 由于肠道微生物群被描述为调节肠道上皮细胞的稳态[29, 30]，我们研究了围产期暴露于食源性 TiO2 是否会影响肠道上皮细胞的稳态[30, 31]、图 2 小鼠围产期暴露于食源性 TiO2 30 天后对结肠微生物群的影响。A-E 野生型雌性小鼠在围产期（包括妊娠期和哺乳期）暴露于二氧化钛（9 毫克/体重/天）。然后在出生后第 30 天图 2 围产期暴露于食源性 TiO2 对出生后第 30 天结肠微生物区系的影响。A-D 野生型雌性小鼠在围产期（包括妊娠期和哺乳期）暴露于二氧化钛（9 毫克/千克体重/天）。出生后第 30 天，幼鼠被处死，并通过 16S rRNA 基因测序监测结肠粘膜相关微生物区系的结构（B-D）C-D 出生后第 30 天，暴露或未暴露于食源性 TiV 的小鼠结肠微生物区系的组成（C）和受显著干扰的细菌属的折叠变化 2（D）。S5A，B）在出生后 50 天，暴露于 TiO2 只增加了 Muc2 的水平（附加文件 5：图 5）。
引用次数: 0
Results from omic approaches in rat or mouse models exposed to inhaled crystalline silica: a systematic review
暴露于吸入结晶二氧化硅的大鼠或小鼠模型的奥米克方法结果：系统综述
IF 1
1区 医学
Q1 Pharmacology, Toxicology and Pharmaceutics
Pub Date : 2024-03-01
DOI: 10.1186/s12989-024-00573-x
Crystalline silica (cSiO2) is a mineral found in rocks; workers from the construction or denim industries are particularly exposed to cSiO2 through inhalation. cSiO2 inhalation increases the risk of silicosis and systemic autoimmune diseases. Inhaled cSiO2 microparticles can reach the alveoli where they induce inflammation, cell death, auto-immunity and fibrosis but the specific molecular pathways involved in these cSiO2 effects remain unclear. This systematic review aims to provide a comprehensive state of the art on omic approaches and exposure models used to study the effects of inhaled cSiO2 in mice and rats and to highlight key results from omic data in rodents also validated in human. The protocol of systematic review follows PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible articles were identified in PubMed, Embase and Web of Science. The search strategy included original articles published after 1990 and written in English which included mouse or rat models exposed to cSiO2 and utilized omic approaches to identify pathways modulated by cSiO2. Data were extracted and quality assessment was based on the SYRCLE’s Risk of Bias tool for animal studies. Rats and male rodents were the more used models while female rodents and autoimmune prone models were less studied. Exposure of animals were both acute and chronic and the timing of outcome measurement through omics approaches were homogeneously distributed. Transcriptomic techniques were more commonly performed while proteomic, metabolomic and single-cell omic methods were less utilized. Immunity and inflammation were the main domains modified by cSiO2 exposure in lungs of mice and rats. Less than 20% of the results obtained in rodents were finally verified in humans. Omic technics offer new insights on the effects of cSiO2 exposure in mice and rats although the majority of data still need to be validated in humans. Autoimmune prone model should be better characterised and systemic effects of cSiO2 need to be further studied to better understand cSiO2-induced autoimmunity. Single-cell omics should be performed to inform on pathological processes induced by cSiO2 exposure.
晶体二氧化硅（cSiO2）是一种存在于岩石中的矿物质；建筑或牛仔布行业的工人尤其容易通过吸入而接触到二氧化硅。吸入的二氧化硅微粒可进入肺泡，诱发炎症、细胞死亡、自身免疫和纤维化，但二氧化硅产生这些影响的具体分子途径仍不清楚。本系统综述旨在全面介绍用于研究小鼠和大鼠吸入的二氧化硅影响的奥米克方法和暴露模型的最新进展，并重点介绍在啮齿类动物中得到验证的奥米克数据的关键结果。系统综述方案遵循 PRISMA（系统综述和元分析首选报告项目）指南。符合条件的文章在 PubMed、Embase 和 Web of Science 中进行了搜索。搜索策略包括1990年后发表的英文原创文章，这些文章包括暴露于二氧化硅的小鼠或大鼠模型，并利用欧米克方法确定二氧化硅调节的途径。根据SYRCLE的动物研究偏倚风险工具提取数据并进行质量评估。大鼠和雄性啮齿类动物是使用较多的模型，而雌性啮齿类动物和自身免疫易感模型的研究较少。动物的暴露既有急性的，也有慢性的，通过 omics 方法测量结果的时间分布也很均匀。转录组技术更常用，而蛋白质组、代谢组和单细胞全息方法则较少使用。免疫和炎症是小鼠和大鼠肺部因接触二氧化硅而改变的主要领域。在啮齿动物身上获得的结果只有不到20%最终在人类身上得到了验证。尽管大部分数据仍需在人体中验证，但海洋学技术为了解小鼠和大鼠接触二氧化硅的影响提供了新的视角。应更好地描述易发生自身免疫的模型，并进一步研究二氧化硅的全身效应，以更好地了解二氧化硅诱导的自身免疫。应进行单细胞组学研究，以了解二氧化硅暴露诱发的病理过程。
引用次数: 0
Zinc oxide nanoparticles exacerbate skin epithelial cell damage by upregulating pro-inflammatory cytokines and exosome secretion in M1 macrophages following UVB irradiation-induced skin injury.
氧化锌纳米颗粒通过上调促炎细胞因子和外泌体分泌，加剧紫外线照射诱发的皮肤损伤后的皮肤上皮细胞损伤。
IF 7.2
1区 医学
Q1 TOXICOLOGY
Pub Date : 2024-02-28
DOI: 10.1186/s12989-024-00571-z
Background: Zinc oxide nanoparticles (ZnONPs) are common materials used in skin-related cosmetics and sunscreen products due to their whitening and strong UV light absorption properties. Although the protective effects of ZnONPs against UV light in intact skin have been well demonstrated, the effects of using ZnONPs on damaged or sunburned skin are still unclear. In this study, we aimed to reveal the detailed underlying mechanisms related to keratinocytes and macrophages exposed to UVB and ZnONPs. Results: We demonstrated that ZnONPs exacerbated mouse skin damage after UVB exposure, followed by increased transepidermal water loss (TEWL) levels, cell death and epithelial thickness. In addition, ZnONPs could penetrate through the damaged epithelium, gain access to the dermis cells, and lead to severe inflammation by activation of M1 macrophage. Mechanistic studies indicated that co-exposure of keratinocytes to UVB and ZnONPs lysosomal impairment and autophagy dysfunction, which increased cell exosome release. However, these exosomes could be taken up by macrophages, which accelerated M1 macrophage polarization. Furthermore, ZnONPs also induced a lasting inflammatory response in M1 macrophages and affected epithelial cell repair by regulating the autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. Conclusions: Our findings propose a new concept for ZnONP-induced skin toxicity mechanisms and the safety issue of ZnONPs application on vulnerable skin. The process involved an interplay of lysosomal impairment, autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. The current finding is valuable for evaluating the effects of ZnONPs for cosmetics applications.
背景：氧化锌纳米粒子（ZnONPs）具有美白和强紫外线吸收特性，是皮肤相关化妆品和防晒产品中常用的材料。虽然 ZnONPs 对完整皮肤紫外线的保护作用已得到充分证实，但对受损或晒伤皮肤使用 ZnONPs 的效果仍不清楚。在这项研究中，我们旨在揭示与暴露于紫外线和 ZnONPs 的角质细胞和巨噬细胞有关的详细内在机制：结果：我们发现 ZnONPs 会加剧 UVB 暴露后小鼠皮肤的损伤，继而增加经表皮失水（TEWL）水平、细胞死亡和上皮厚度。此外，ZnONPs 还能穿透受损的上皮细胞，进入真皮层细胞，并通过激活 M1 巨噬细胞导致严重的炎症。机理研究表明，角质细胞同时暴露于紫外线和 ZnONPs 会导致溶酶体受损和自噬功能障碍，从而增加细胞外泌体的释放。然而，这些外泌体可被巨噬细胞吸收，从而加速了 M1 型巨噬细胞的极化。此外，ZnONPs还通过调节自噬介导的NLRP3炎性体和巨噬细胞外泌体的分泌，诱导M1巨噬细胞产生持久的炎症反应，并影响上皮细胞的修复：我们的研究结果为壬基酚诱导的皮肤毒性机制以及壬基酚应用于脆弱皮肤的安全性问题提出了一个新概念。这一过程涉及溶酶体损伤、自噬介导的 NLRP3 炎性体和巨噬细胞外泌体的相互作用。目前的发现对于评估 ZnONPs 在化妆品中的应用效果很有价值。
引用次数: 0
Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles.
基因不同的小鼠品系在联合接触二氧化硅和柴油机废气颗粒后肺部毒性和自身抗体形成的差异。
IF 7.2
1区 医学
Q1 TOXICOLOGY
Pub Date : 2024-02-27
DOI: 10.1186/s12989-024-00569-7
Background: Inhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory and systemic health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of occupational-level silica and ambient-level DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization. Results: The findings highlight the distinct effects of silica and diesel exhaust particles (DEP) on lung injury, inflammation, and autoantibody formation in C57BL/6J and NOD/ShiLtJ mice. Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside mild fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Moreover, antinuclear antibodies correlated with extent of lung inflammation in NOD/ShiLTJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. However, aside from contributing to airway hyperreactivity specifically in NOD/ShiLtJ mice, the ambient-level DEP did not significantly amplify the effects induced by silica. There was no evidence of synergistic or additive interaction between these specific doses of silica and DEP in inducing lung damage or inflammation in either of the mouse strains. Conclusion: Mouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of ambient-level DEP on these silica-induced effects was minimal.
背景：吸入空气中的微粒物质（如二氧化硅和柴油机废气微粒）会对呼吸系统和全身健康造成严重的长期危害。接触二氧化硅可导致矽肺病和全身性自身免疫性疾病，而接触 DEP 则与哮喘和癌症有关。采矿业中常见的二氧化硅和二乙基乙基化合物的联合暴露可能会产生更严重的影响。本研究调查了职业水平的二氧化硅和环境水平的二乙基乙基吡咯烷酮对两个基因不同的小鼠品系的肺损伤、炎症和自身抗体形成的单独和联合影响，从而了解遗传易感性、微粒暴露和疾病结果之间的相互作用。小鼠经口咽吸入二氧化硅和柴油机废气颗粒。对肺损伤和宿主反应的评估包括体内肺部微型计算机断层扫描、肺功能测试、支气管肺泡灌洗液分析（包括炎症细胞因子和抗核抗体）以及颗粒共聚焦组织病理学：结果：研究结果表明，二氧化硅和柴油机废气颗粒（DEP）对 C57BL/6J 和 NOD/ShiLtJ 小鼠的肺损伤、炎症和自身抗体形成有不同的影响。暴露于二氧化硅会引起成熟的炎症反应，表现为炎症浸润、细胞因子和趋化因子的释放，以及轻度纤维化，表现为 C57BL/6J 和 NOD/ShilLtJ 小鼠肺部的胶原沉积。值得注意的是，这些品系在呼吸功能和肺容量方面表现出不同的反应，这是由微型计算机断层扫描评估得出的结果。此外，二氧化硅暴露会诱发气道高反应性和支气管肺泡灌洗液中抗核抗体水平的升高，这在 NOD/ShiLtJ 小鼠中尤为突出。此外，抗核抗体与 NOD/ShiLTJ 小鼠肺部炎症的程度相关。肺组织分析显示了含有 DEP 的巨噬细胞以及二氧化硅和 DEP 颗粒的共定位。然而，除了导致 NOD/ShiLtJ 小鼠气道过度反应外，环境水平的 DEP 并没有显著放大二氧化硅诱导的效应。没有证据表明这些特定剂量的二氧化硅和 DEP 在诱发小鼠肺损伤或炎症方面存在协同或叠加作用：结论：小鼠品系的变化对二氧化硅诱导的肺部病变的发展有很大影响。此外，环境水平的 DEP 对这些二氧化硅诱导效应的额外影响微乎其微。
引用次数: 0
Effective density of inhaled environmental and engineered nanoparticles and its impact on the lung deposition and dosimetry
吸入环境纳米粒子和工程纳米粒子的有效密度及其对肺沉积和剂量测定的影响
IF 1
1区 医学
Q1 Pharmacology, Toxicology and Pharmaceutics
Pub Date : 2024-02-17
DOI: 10.1186/s12989-024-00567-9
Airborne environmental and engineered nanoparticles (NPs) are inhaled and deposited in the respiratory system. The inhaled dose of such NPs and their deposition location in the lung determines their impact on health. When calculating NP deposition using particle inhalation models, a common approach is to use the bulk material density, ρb, rather than the effective density, ρeff. This neglects though the porous agglomerate structure of NPs and may result in a significant error of their lung-deposited dose and location. Here, the deposition of various environmental NPs (aircraft and diesel black carbon, wood smoke) and engineered NPs (silica, zirconia) in the respiratory system of humans and mice is calculated using the Multiple-Path Particle Dosimetry model accounting for their realistic structure and effective density. This is done by measuring the NP ρeff which was found to be up to one order of magnitude smaller than ρb. Accounting for the realistic ρeff of NPs reduces their deposited mass in the pulmonary region of the respiratory system up to a factor of two in both human and mouse models. Neglecting the ρeff of NPs does not alter significantly the distribution of the deposited mass fractions in the human or mouse respiratory tract that are obtained by normalizing the mass deposited at the head, tracheobronchial and pulmonary regions by the total deposited mass. Finally, the total deposited mass fraction derived this way is in excellent agreement with those measured in human studies for diesel black carbon. The doses of inhaled NPs are overestimated by inhalation particle deposition models when the ρb is used instead of the real-world effective density which can vary significantly due to the porous agglomerate structure of NPs. So the use of realistic ρeff, which can be measured as described here, is essential to determine the lung deposition and dosimetry of inhaled NPs and their impact on public health.
空气中的环境纳米粒子和工程纳米粒子（NPs）会被吸入并沉积在呼吸系统中。此类 NP 的吸入剂量及其在肺部的沉积位置决定了它们对健康的影响。在使用粒子吸入模型计算 NP 沉积时，常见的方法是使用块状材料密度 ρb 而不是有效密度 ρeff。这种方法忽略了 NPs 的多孔团聚结构，可能会导致 NPs 在肺部沉积的剂量和位置出现重大误差。在这里，我们使用多径粒子剂量测定模型计算了各种环境 NPs（飞机和柴油机黑碳、木烟）和工程 NPs（二氧化硅、氧化锆）在人类和小鼠呼吸系统中的沉积情况，并考虑了它们的实际结构和有效密度。这是通过测量 NP ρeff 来实现的，结果发现 NP ρeff 比 ρb 小一个数量级。在人类和小鼠模型中，考虑到 NP 的实际 ρeff 会使其在呼吸系统肺部沉积的质量减少达 2 倍。通过将头部、气管支气管和肺部沉积的质量与总沉积质量进行归一化处理，忽略 NPs 的 ρeff 并不会显著改变沉积质量分数在人类或小鼠呼吸道中的分布。最后，这种方法得出的总沉积质量分数与人类研究中测得的柴油黑碳质量分数非常一致。如果使用 ρb 而不是实际有效密度，吸入粒子沉积模型就会高估吸入 NPs 的剂量。因此，要确定吸入 NPs 的肺沉积和剂量测定及其对公众健康的影响，就必须使用实际的 ρeff （可按本文所述方法测量）。
引用次数: 0
Particulate matter from car exhaust alters function of human iPSC-derived microglia.
汽车尾气中的微粒物质会改变人类 iPSC 衍生小胶质细胞的功能。
IF 7.2
1区 医学
Q1 TOXICOLOGY
Pub Date : 2024-02-15
DOI: 10.1186/s12989-024-00564-y
Background: Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Alzheimer's disease. Inhaled components of PM may directly invade the brain via the olfactory route, or act through peripheral system responses resulting in inflammation and oxidative stress in the brain. Microglia are the immune cells of the brain implicated in the progression of neurodegenerative diseases. However, it remains unknown how PM affects live human microglia. Results: Here we show that two different PMs derived from exhausts of cars running on EN590 diesel or compressed natural gas (CNG) alter the function of human microglia-like cells in vitro. We exposed human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGLs) to traffic related PMs and explored their functional responses. Lower concentrations of PMs ranging between 10 and 100 µg ml-1 increased microglial survival whereas higher concentrations became toxic over time. Both tested pollutants impaired microglial phagocytosis and increased secretion of a few proinflammatory cytokines with distinct patterns, compared to lipopolysaccharide induced responses. iMGLs showed pollutant dependent responses to production of reactive oxygen species (ROS) with CNG inducing and EN590 reducing ROS production. Conclusions: Our study indicates that traffic-related air pollutants alter the function of human microglia and warrant further studies to determine whether these changes contribute to adverse effects in the brain and on cognition over time. This study demonstrates human iPSC-microglia as a valuable tool to study functional microglial responses to environmental agents.
背景：空气污染被认为是神经系统疾病的一个新兴环境风险因素。大规模流行病学研究表明，与交通相关的颗粒物（PM）会损害认知功能，并增加阿尔茨海默病等神经退行性疾病的发病率。吸入的可吸入颗粒物成分可能通过嗅觉途径直接侵入大脑，也可能通过外周系统反应导致大脑炎症和氧化应激。小胶质细胞是大脑的免疫细胞，与神经退行性疾病的进展有关联。然而，人们仍然不知道 PM 如何影响活的人类小胶质细胞：结果：我们在这里展示了两种不同的可吸入颗粒物，它们来自使用 EN590 柴油或压缩天然气（CNG）的汽车尾气，会改变体外人类小胶质细胞的功能。我们将人类诱导多能干细胞（iPSC）衍生的小胶质细胞（iMGLs）暴露于与交通相关的可吸入颗粒物中，并探索了它们的功能反应。10 至 100 µg ml-1 的低浓度可吸入颗粒物可提高小胶质细胞的存活率，而较高浓度的可吸入颗粒物则会随着时间的推移而产生毒性。与脂多糖诱导的反应相比，两种测试污染物都会损害小胶质细胞的吞噬功能，并以不同的模式增加一些促炎细胞因子的分泌。iMGLs对活性氧（ROS）的产生表现出污染物依赖性反应，CNG会诱导ROS的产生，而EN590则会减少ROS的产生：我们的研究表明，与交通相关的空气污染物会改变人类小胶质细胞的功能，因此有必要进行进一步研究，以确定这些变化是否会随着时间的推移对大脑和认知能力产生不利影响。这项研究表明，人类 iPSC-小胶质细胞是研究小胶质细胞对环境因素的功能性反应的重要工具。
引用次数: 0
  Book学术文献互助群 群 号：481959085 
Book学术提供免费学术资源搜索服务，方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
京公网安备 11010802042870号
京ICP备2023020795号-1
|
扫码关注我们
求助内容：
应助结果提醒方式：