| Author | Ciambarella, Bianca Torres | |
| Author | Almeida, Gláucia Souza de | |
| Author | Dias, Davidson Furtado | |
| Author | Trentin, Patrícia Gonçalves | |
| Author | Santos, Tatiane Perez Oliveira dos | |
| Author | Ferreira, Tatiana Paula Teixeira | |
| Author | Arantes, Ana Carolina Santos de | |
| Author | Azevedo, Rodrigo Bandeira de | |
| Author | Fernandes, Andrey Junio Moreira | |
| Author | Martins, Marco Aurélio | |
| Author | Martins, Patrícia Machado Rodrigues e Silva | |
| Access date | 2025-02-20T14:41:56Z | |
| Available date | 2025-02-20T14:41:56Z | |
| Document date | 2025 | |
| Citation | CIAMBARELLA, Bianca Torres et al. TNF-alpha mediates airway hyperreactivity in silicotic mice: effect of thalidomide treatment. European Journal of Pharmacology, v. 990, n. 177263, p. 1-12, 5 Mar. 2025. | |
| ISSN | 0014-2999 | |
| URI | https://www.arca.fiocruz.br/handle/icict/68655 | |
| Description | Produção científica do Laboratório de Inflamação. | pt_BR |
| Sponsorship | We would like to acknowledge the financial support of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (315661/2021-6) (CNPq), Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) (E−26/201.042/2022), and Fiocruz. | |
| Language | eng | en_US |
| Publisher | Elsevier | |
| Rights | restricted access | |
| Title | TNF-alpha mediates airway hyperreactivity in silicotic mice: effect of thalidomide treatment | en_US |
| Type | Article | |
| DOI | 10.1016/j.ejphar.2025.177263 | |
| Abstract | Inhalation of crystalline silica particles causes silicosis, which is a severe inflammatory lung disease that is associated with granulomatous and fibrotic responses. We investigated whether silica-induced silicosis might promote airway hyperreactivity (AHR) and the role of TNF-α and thalidomide in this process. Mice received an intranasal instillation of silica particles (1.25, 5, and 10 mg/mouse) and given methacholine on days 2, 7, and 28 after provocation or 5-HT challenges on day 7 after provocation. AHR was assessed using invasive whole-body plethysmography. Lung-tissue samples were collected for TNF-α measurements and histological analyses. Thalidomide was given orally from days 21–27 after silica administration. We found that following aerosolised methacholine or 5-HT treatment, a state of AHR was induced with silica-particle amounts of 5 and 10 mg/mouse, but not 1.25 mg/mouse. The effect was apparent within 2 days and remained for at least 28 days. Silica-particle amounts of 5 and 10 mg/mouse also induced significant granuloma response correlating with the silica required to induce AHR. In addition, a parallel was also observed between the elevation of lung tissue levels of TNF-α and AHR. Notably, silica-induced granulomatous and AHR responses were abolished in TNFR1‾/‾ mice compared to wild-type mice. Moreover, the blockade of ongoing TNF-α generation by thalidomide prevented both events. Our findings suggest that exposure of mice to silica particles leads to a granulomatous lung response marked by non-specific AHR induced by TNF-α. In addition, the results indicate that thalidomide can control silica-induced pathological features of the lungs by blocking TNF-α generation. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
| Subject | Silicosis | en_US |
| Subject | TNF-Alpha | en_US |
| Subject | Fibrosis | en_US |
| Subject | Airway hyperreactivity | en_US |
| Subject | Thalidomide | en_US |
| e-ISSN | 1879-0712 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
| xmlui.metadata.dc.subject.ods | 08 Trabalho decente e crescimento econômico | |
| xmlui.metadata.dc.subject.ods | 09 Indústria, inovação e infraestrutura | |
| xmlui.metadata.dc.subject.ods | 12 Consumo e produção responsáveis | |
