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Thymic stromal lymphopoietin (TSLP) and Toluene-diisocyanate-induced airway inflammation: Alleviation by TSLP neutralizing antibody.
- Source :
-
Toxicology letters [Toxicol Lett] 2019 Dec 15; Vol. 317, pp. 59-67. Date of Electronic Publication: 2019 Sep 29. - Publication Year :
- 2019
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Abstract
- Toluene-diisocyanate (TDI) is mainly used in the manufacturing process of polyurethane foams, and is a potent inducer of occupational asthma characterized by airway inflammation and airway hyperreactivity. Thymic stromal lymphopoietin (TSLP) plays an important role in the development of asthma, and correlating with the differentiation of Th2 and Th17 cells. However, the role of TSLP in TDI-induced asthma remains unclear. In this study, 96 TDI-exposed workers as well as a mouse model of TDI-induced asthma were investigated. The air exposure assessment result of TDI in the workplace showed that workers were exposed to inhalation of a very high concentration of TDI, approximately 8 times the recommended level, leading to a decrease in pulmonary function and an increase in inflammatory cells, as well as TSLP and IgE levels in the supernatant of sputum obtained from exposed workers. In order to further investigate the role of TSLP in the pathogenesis of TDI-induced asthma, a mouse model of TDI-induced asthma was also employed. Histopathological analysis of mouse lung and bronchus showed an obvious infiltration of inflammatory cells around the bronchus. The levels of inflammatory cells, IFN-γ, IL-4 and IL-17 in bronchoalveolar lavage fluid (BALF), the expression levels of TSLP protein and ROR-γt and IL-17 mRNA in mouse lung tissues were also significantly increased. However, after treatment with TSLP neutralizing antibody (TSLP-Ab), the degree of pulmonary and bronchial inflammation in mice was significantly alleviated, and the levels of inflammatory cells, IFN-γ, IL-4 and IL-17 in BALF, and the expression levels of ROR-γt and IL-17 mRNA in lung tissue were significantly decreased. Our data shows that TSLP plays an important role in the pathogenesis of TDI-induced asthma, and that TSLP-Ab can effectively alleviate TDI-induced airway inflammation of asthma.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Adult
Animals
Asthma chemically induced
Asthma immunology
Asthma metabolism
Case-Control Studies
Cross-Sectional Studies
Cytokines immunology
Cytokines metabolism
Humans
Immunoglobulin E immunology
Inflammation Mediators immunology
Inflammation Mediators metabolism
Inhalation Exposure adverse effects
Interleukin-17 immunology
Lung immunology
Lung metabolism
Male
Mice, Inbred BALB C
Middle Aged
Occupational Exposure adverse effects
Pneumonia chemically induced
Pneumonia immunology
Pneumonia metabolism
Signal Transduction drug effects
Thymic Stromal Lymphopoietin
Anti-Inflammatory Agents pharmacology
Antibodies, Neutralizing pharmacology
Asthma prevention & control
Cytokines antagonists & inhibitors
Inflammation Mediators antagonists & inhibitors
Lung drug effects
Pneumonia prevention & control
Toluene 2,4-Diisocyanate adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 317
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 31577921
- Full Text :
- https://doi.org/10.1016/j.toxlet.2019.09.021