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

Autor: Dos Santos TM; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil. tabatamaruyama@gmail.com.; Hospital Sírio Libanês, São Paulo, SP, Brazil. tabatamaruyama@gmail.com., Righetti RF; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil.; Hospital Sírio Libanês, São Paulo, SP, Brazil., do Nascimento Camargo L; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil.; Hospital Sírio Libanês, São Paulo, SP, Brazil., Leick EA; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil., Fukuzaki S; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil.; Hospital Alemão Oswaldo Cruz, São Paulo, Brazil., de Campos EC; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil.; Hospital Sírio Libanês, São Paulo, SP, Brazil., Galli TT; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil., Saraiva-Romanholo BM; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil.; University City of São Paulo (UNICID), São Paulo, Brazil., da Silva LLS; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil., Barbosa JAS; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil.; Hospital Sírio Libanês, São Paulo, SP, Brazil., João JMLG; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil.; Hospital Sírio Libanês, São Paulo, SP, Brazil., Prado CM; Department of Biosciences, Universidade Federal de São Paulo, Santos, Brazil., de Rezende BG; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil., Bourotte CLM; Instituto de Geociências, Universidade de São Paulo, São Paulo, Brasil., Dos Santos Lopes FDTQ; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil., de Arruda Martins M; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil., Bensenor IM; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil., de Oliveira Cirillo JV; University City of São Paulo (UNICID), São Paulo, Brazil., Bezerra SKM; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil., Silva FJA; Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória, Vitória, Brazil., Paulo MSL; Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória, Vitória, Brazil., Lotufo PA; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil., Lopes Calvo Tibério IF; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil.
Jazyk: angličtina
Zdroj: Journal of inflammation (London, England) [J Inflamm (Lond)] 2024 Jul 03; Vol. 21 (1), pp. 24. Date of Electronic Publication: 2024 Jul 03.
DOI: 10.1186/s12950-024-00399-6
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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