The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association

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Arquivos
art_CERVILHA_The_Th17Treg_Cytokine_Imbalance_in_Chronic_Obstructive_Pulmonary_2019.PDF (2.52 MB)
Citações na Scopus
31
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE PUBLISHING GROUP
Autores
OLIVEIRA-JUNIOR, Manoel C.
Citação
SCIENTIFIC REPORTS, v.9, article ID 1921, 13p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
We proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 +/- 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 mu l) or lipopolysaccharide (LPS) (1 mg/kg in 50 mu l of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4(+) and CD8(+) T cells, Treg cells, and IL-10(+) and IL-17(+) cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-gamma, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4(+) and CD8(+) T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17(+) cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5(+) cells corroborated the increased numbers of IL-17(+) and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL10(+) cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model.
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URI
https://observatorio.fm.usp.br/handle/OPI/31206
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/05
Artigos e Materiais de Revistas Científicas - LIM/12
Artigos e Materiais de Revistas Científicas - LIM/20