Effect of VAChT reduction on lung alterations induced by exposure to iron particles in an asthma model.

IF 4.4 3区医学 Q2 IMMUNOLOGY

Journal of Inflammation-London Pub Date : 2024-07-03 DOI:10.1186/s12950-024-00399-6

Tabata Maruyama Dos Santos, Renato Fraga Righetti, Leandro do Nascimento Camargo, Edna Aparecida Leick, Silvia Fukuzaki, Elaine Cristina de Campos, Thiago Tafarel Galli, Beatriz Mangueira Saraiva-Romanholo, Luana Laura Sales da Silva, Jéssica Anastácia Silva Barbosa, Juliana Morelli Lopes Gonçalves João, Carla Máximo Prado, Bianca Goulart de Rezende, Christine Laure Marie Bourotte, Fernanda Degobbi Tenorio Quirino Dos Santos Lopes, Milton de Arruda Martins, Isabela M Bensenor, João Vitor de Oliveira Cirillo, Suellen Karoline Moreira Bezerra, Fabio José Alencar Silva, Marcela Souza Lima Paulo, Paulo A Lotufo, Iolanda de Fátima Lopes Calvo Tibério

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引用次数: 0

Abstract

Introduction: Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood.

Methods: One hundred eight animals were divided into 18 groups (6 animals). Groups included: wild type mice (WT), genetically modified with reduced VAChT (VAChTKD), and those sensitized with ovalbumin (VAChTKDA), exposed to metal powder due to iron pelletizing in mining company (Local1) or 3.21 miles away from a mining company (Local2) in their locations for 2 weeks during summer and winter seasons. It was analyzed for hyperresponsivity, inflammation, remodeling, oxidative stress responses and the cholinergic system.

Results: During summer, animals without changes in the cholinergic system revealed that Local1 exposure increased the hyperresponsiveness (%Rrs, %Raw), and inflammation (IL-17) relative to vivarium animals, while animals exposed to Local2 also exhibited elevated IL-17. During winter, animals without changes in the cholinergic system revealed that Local2 exposure increased the hyperresponsiveness (%Rrs) relative to vivarium animals. Comparing the exposure local of these animals during summer, animals exposed to Local1 showed elevated %Rrs, Raw, and IL-5 compared to Local 2, while in winter, Local2 exposure led to more IL-17 than Local1. Animals with VAChT attenuation displayed increased %Rrs, NFkappaB, IL-5, and IL-13 but reduced alpha-7 compared to animals without changes in the cholinergic system WT. Animals with VAChT attenuation and asthma showed increased the hyperresponsiveness, all inflammatory markers, remodeling and oxidative stress compared to animals without chronic lung inflammation. Exposure to Local1 exacerbated the hyperresponsiveness, oxidative stressand inflammation in animals with VAChT attenuation associated asthma, while Local2 exposure led to increased inflammation, remodeling and oxidative stress.

Conclusions: Reduced cholinergic signaling amplifies lung inflammation in a model of chronic allergic lung inflammation. Furthermore, when associated with pollution, it can aggravate specific responses related to inflammation, oxidative stress, and remodeling.

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减少 VAChT 对哮喘模型中因接触铁微粒而引起的肺部变化的影响

导言：污染危害哮喘患者的健康。人们对抗炎性胆碱能通路在与污染相关的慢性过敏性炎症中的作用知之甚少：方法：将 18 只动物分为 18 组（6 只）。各组包括：野生型小鼠（WT）、VAChT减少的转基因小鼠（VAChTKD）和使用卵清蛋白致敏的小鼠（VAChTKDA），在夏季和冬季暴露于矿业公司（Local1）或距离矿业公司3.21英里的地方（Local2）的铁造粒产生的金属粉末中2周。对动物的高反应性、炎症、重塑、氧化应激反应和胆碱能系统进行了分析：结果：在夏季，胆碱能系统未发生变化的动物显示，与活体动物相比，接触局部1会增加高反应性（%Rrs、%Raw）和炎症（IL-17），而接触局部2的动物也表现出IL-17升高。在冬季，胆碱能系统未发生变化的动物显示，与活体动物相比，暴露于本地 2 的动物会增加高反应性（%Rrs）。比较这些动物在夏季的暴露部位，暴露于局部1的动物比暴露于局部2的动物显示出更高的反应性%Rrs、Raw和IL-5，而在冬季，暴露于局部2的动物比暴露于局部1的动物产生更多的IL-17。与胆碱能系统WT未发生变化的动物相比，VAChT衰减的动物显示出%Rrs、NFkappaB、IL-5和IL-13升高，但α-7降低。与没有慢性肺部炎症的动物相比，VAChT衰减和哮喘动物的高反应性、所有炎症标志物、重塑和氧化应激均有所增加。暴露于Local1会加剧VAChT衰减伴哮喘动物的高反应性、氧化应激和炎症，而暴露于Local2会导致炎症、重塑和氧化应激增加：结论：在慢性过敏性肺部炎症模型中，胆碱能信号传导减少会扩大肺部炎症。结论：在慢性过敏性肺部炎症模型中，胆碱能信号的降低会放大肺部炎症，而且当胆碱能信号与污染相关时，会加重与炎症、氧化应激和重塑相关的特定反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Inflammation-London IMMUNOLOGY-

CiteScore

7.90

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Inflammation welcomes research submissions on all aspects of inflammation. The five classical symptoms of inflammation, namely redness (rubor), swelling (tumour), heat (calor), pain (dolor) and loss of function (functio laesa), are only part of the story. The term inflammation is taken to include the full range of underlying cellular and molecular mechanisms involved, not only in the production of the inflammatory responses but, more importantly in clinical terms, in the healing process as well. Thus the journal covers molecular, cellular, animal and clinical studies, and related aspects of pharmacology, such as anti-inflammatory drug development, trials and therapeutic developments. It also considers publication of negative findings. Journal of Inflammation aims to become the leading online journal on inflammation and, as online journals replace printed ones over the next decade, the main open access inflammation journal. Open access guarantees a larger audience, and thus impact, than any restricted access equivalent, and increasingly so, as the escalating costs of printed journals puts them outside University budgets. The unrestricted access to research findings in inflammation aids in promoting dynamic and productive dialogue between industrial and academic members of the inflammation research community, which plays such an important part in the development of future generations of anti-inflammatory therapies.