IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13

IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13

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 overe...

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Main Authors: Sawada, Masanori, Kawayama, Tomotaka, Imaoka, Haruki, Sakazaki, Yuki, Oda, Hanako, Takenaka, Shin-ichi, Kaku, Yoichiro, Azuma, Koichi, Tajiri, Morihiro, Edakuni, Nobutaka, Okamoto, Masaki, Kato, Seiya, Hoshino, Tomoaki
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558507/
id pubmed-3558507
recordtype oai_dc
spelling pubmed-35585072013-02-04 IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13 Sawada, Masanori Kawayama, Tomotaka Imaoka, Haruki Sakazaki, Yuki Oda, Hanako Takenaka, Shin-ichi Kaku, Yoichiro Azuma, Koichi Tajiri, Morihiro Edakuni, Nobutaka Okamoto, Masaki Kato, Seiya Hoshino, Tomoaki Research Article 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. Public Library of Science 2013-01-29 /pmc/articles/PMC3558507/ /pubmed/23382928 http://dx.doi.org/10.1371/journal.pone.0054623 Text en © 2013 Sawada et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Sawada, Masanori
Kawayama, Tomotaka
Imaoka, Haruki
Sakazaki, Yuki
Oda, Hanako
Takenaka, Shin-ichi
Kaku, Yoichiro
Azuma, Koichi
Tajiri, Morihiro
Edakuni, Nobutaka
Okamoto, Masaki
Kato, Seiya
Hoshino, Tomoaki
spellingShingle Sawada, Masanori
Kawayama, Tomotaka
Imaoka, Haruki
Sakazaki, Yuki
Oda, Hanako
Takenaka, Shin-ichi
Kaku, Yoichiro
Azuma, Koichi
Tajiri, Morihiro
Edakuni, Nobutaka
Okamoto, Masaki
Kato, Seiya
Hoshino, Tomoaki
IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13
author_facet Sawada, Masanori
Kawayama, Tomotaka
Imaoka, Haruki
Sakazaki, Yuki
Oda, Hanako
Takenaka, Shin-ichi
Kaku, Yoichiro
Azuma, Koichi
Tajiri, Morihiro
Edakuni, Nobutaka
Okamoto, Masaki
Kato, Seiya
Hoshino, Tomoaki
author_sort Sawada, Masanori
title IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13
title_short IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13
title_full IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13
title_fullStr IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13
title_full_unstemmed IL-18 Induces Airway Hyperresponsiveness and Pulmonary Inflammation via CD4+ T Cell and IL-13
title_sort il-18 induces airway hyperresponsiveness and pulmonary inflammation via cd4+ t cell and il-13
description 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.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558507/
_version_ 1611950632730624000

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