Essential role of IL-23 in the development of acute exacerbation of pulmonary fibrosis

Acute exacerbation of idiopathic pulmonary fibrosis has a poor prognosis associated with neutrophilic inflammation. Interleukin-23 is a proinflammatory cytokine involved in neutrophilic inflammation. However, little is known about its role in acute exacerbation of pulmonary fibrosis. This study was performed to determine the role of interleukin-23 in acute exacerbation of pulmonary fibrosis. For assessment of acute exacerbation of pulmonary fibrosis, mice were intratracheally administered bleomycin followed by lipopolysaccharide. Inflammatory cells, cytokine levels, and morphological morphometry of the lungs were analyzed. Cytokine levels were measured in the bronchoalveolar lavage fluid of idiopathic pulmonary fibrosis patients with or without acute exacerbation. Interleukin-23, -17A, and -22 levels were increased in the airway of mice with acute exacerbation of pulmonary fibrosis. Interleukin-23p19-deficient mice with acute exacerbation of pulmonary fibrosis had markedly reduced airway inflammation and fibrosis associated with decreased levels of interleukin-17A and -22 compared with wild-type mice. Treatment with an anti-interleukin-23 antibody attenuated airway inflammation and fibrosis and reduced interleukin-17A and -22 levels in mice with acute exacerbation of pulmonary fibrosis. T-helper type 17 cells were the predominant source of interleukin-17A in mice with acute exacerbation of pulmonary fibrosis. Interleukin-23 levels in bronchoalveolar lavage fluid tended to be higher in idiopathic pulmonary fibrosis patients with than without acute exacerbation. The data presented here suggest that interleukin-23 is essential for the development of acute exacerbation of pulmonary fibrosis and that blockade of interleukin-23 may be a new therapeutic strategy for acute exacerbation of pulmonary fibrosis.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:321

Enthalten in:

American journal of physiology. Lung cellular and molecular physiology - 321(2021), 5 vom: 01. Nov., Seite L925-L940

Sprache:

Englisch

Beteiligte Personen:

Senoo, Satoru [VerfasserIn]
Taniguchi, Akihiko [VerfasserIn]
Itano, Junko [VerfasserIn]
Oda, Naohiro [VerfasserIn]
Morichika, Daisuke [VerfasserIn]
Fujii, Utako [VerfasserIn]
Guo, Lili [VerfasserIn]
Sunami, Ryota [VerfasserIn]
Kanehiro, Arihiko [VerfasserIn]
Tokioka, Fumiaki [VerfasserIn]
Yoshimura, Akihiko [VerfasserIn]
Kiura, Katsuyuki [VerfasserIn]
Maeda, Yoshinobu [VerfasserIn]
Miyahara, Nobuaki [VerfasserIn]

Links:

Volltext

Themen:

Idiopathic pulmonary fibrosis
Innate lymphoid cells
Interleukin-17
Interleukin-23
Interleukins
Journal Article
Lipopolysaccharide
Research Support, Non-U.S. Gov't
T-helper type 17 cells

Anmerkungen:

Date Completed 26.11.2021

Date Revised 26.11.2021

published: Print-Electronic

figshare: 10.6084/m9.figshare.13271417

Citation Status MEDLINE

doi:

10.1152/ajplung.00582.2020

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM330669222