Title |
IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13
|
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Published in |
PLOS ONE, January 2013
|
DOI | 10.1371/journal.pone.0054623 |
Pubmed ID | |
Authors |
Masanori Sawada, Tomotaka Kawayama, Haruki Imaoka, Yuki Sakazaki, Hanako Oda, Shin-ichi Takenaka, Yoichiro Kaku, Koichi Azuma, Morihiro Tajiri, Nobutaka Edakuni, Masaki Okamoto, Seiya Kato, Tomoaki Hoshino |
Abstract |
IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases including pulmonary infection, pulmonary fibrosis, lung injury and chronic obstructive pulmonary disease (COPD). However, it is unknown whether IL-18 plays any role in the pathogenesis of asthma. We hypothesized that overexpression of mature IL-18 protein in the lungs may exacerbate disease activities of asthma. We established lung-specific IL-18 transgenic mice on a Balb/c genetic background. Female mice sensitized- and challenged- with antigen (ovalbumin) were used as a mouse asthma model. Pulmonary inflammation and emphysema were not observed in the lungs of naïve transgenic mice. However, airway hyperresponsiveness and airway inflammatory cells accompanied with CD4(+) T cells, CD8(+) T cells, eosinophils, neutrophils, and macrophages were significantly increased in ovalbumin-sensitized and challenged transgenic mice, as compared to wild type Balb/c mice. We also demonstrate that IL-18 induces IFN-γ, IL-13, and eotaxin in the lungs of ovalbumin-sensitized and challenged transgenic mice along with an increase in IL-13 producing CD4(+) T cells. Treatment with anti-CD4 monoclonal antibody or deletion of the IL-13 gene improves ovalbumin-induced airway hyperresponsiveness and reduces airway inflammatory cells in transgenic mice. Overexpressing the IL-18 protein in the lungs induces type 1 and type 2 cytokines and airway inflammation, and results in increasing airway hyperresponsiveness via CD4(+) T cells and IL-13 in asthma. |
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Geographical breakdown
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Germany | 1 | 2% |
Unknown | 40 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 7 | 17% |
Other | 6 | 14% |
Researcher | 5 | 12% |
Student > Ph. D. Student | 4 | 10% |
Student > Doctoral Student | 3 | 7% |
Other | 8 | 19% |
Unknown | 9 | 21% |
Readers by discipline | Count | As % |
---|---|---|
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Agricultural and Biological Sciences | 8 | 19% |
Immunology and Microbiology | 4 | 10% |
Biochemistry, Genetics and Molecular Biology | 3 | 7% |
Psychology | 1 | 2% |
Other | 2 | 5% |
Unknown | 13 | 31% |