IL-23 Is essential for the development of Elastase-induced pulmonary inflammation and emphysema

Utako Fujii, Nobuaki Miyahara, Akihiko Taniguchi, Koichi Waseda, Daisuke Morichika, Etsuko Kurimoto, Hikari Koga, Mikio Kataoka, Erwin W. Gelfand, Daniel J. Cua, Akihiko Yoshimura, Mitsune Tanimoto, Arihiko Kanehiro

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-232/2) and wild-Type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-232/2 mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid ofWTmice was attenuated in IL-232/2 mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.

Original languageEnglish
Pages (from-to)697-707
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume55
Issue number5
DOIs
Publication statusPublished - Nov 1 2016

Fingerprint

Interleukin-23
Pulmonary Emphysema
Pancreatic Elastase
Pneumonia
Swine
Interleukin-17
Emphysema
Interleukin-2
Th17 Cells
Lung
Bronchoalveolar Lavage Fluid
Interleukin-23 Subunit p19
Chemokine CXCL2
Fluids
Keratinocytes
Compliance
Disease Progression
Monoclonal Antibodies
Cytokines
Therapeutics

Keywords

  • Chronic obstructive pulmonary disease
  • IL-17
  • Th17

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

IL-23 Is essential for the development of Elastase-induced pulmonary inflammation and emphysema. / Fujii, Utako; Miyahara, Nobuaki; Taniguchi, Akihiko; Waseda, Koichi; Morichika, Daisuke; Kurimoto, Etsuko; Koga, Hikari; Kataoka, Mikio; Gelfand, Erwin W.; Cua, Daniel J.; Yoshimura, Akihiko; Tanimoto, Mitsune; Kanehiro, Arihiko.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 55, No. 5, 01.11.2016, p. 697-707.

Research output: Contribution to journalArticle

Fujii, U, Miyahara, N, Taniguchi, A, Waseda, K, Morichika, D, Kurimoto, E, Koga, H, Kataoka, M, Gelfand, EW, Cua, DJ, Yoshimura, A, Tanimoto, M & Kanehiro, A 2016, 'IL-23 Is essential for the development of Elastase-induced pulmonary inflammation and emphysema', American Journal of Respiratory Cell and Molecular Biology, vol. 55, no. 5, pp. 697-707. https://doi.org/10.1165/rcmb.2016-0015OC
Fujii, Utako ; Miyahara, Nobuaki ; Taniguchi, Akihiko ; Waseda, Koichi ; Morichika, Daisuke ; Kurimoto, Etsuko ; Koga, Hikari ; Kataoka, Mikio ; Gelfand, Erwin W. ; Cua, Daniel J. ; Yoshimura, Akihiko ; Tanimoto, Mitsune ; Kanehiro, Arihiko. / IL-23 Is essential for the development of Elastase-induced pulmonary inflammation and emphysema. In: American Journal of Respiratory Cell and Molecular Biology. 2016 ; Vol. 55, No. 5. pp. 697-707.
@article{7a73be2ce1e04a5c82911982c012aba7,
title = "IL-23 Is essential for the development of Elastase-induced pulmonary inflammation and emphysema",
abstract = "We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-232/2) and wild-Type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-232/2 mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid ofWTmice was attenuated in IL-232/2 mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.",
keywords = "Chronic obstructive pulmonary disease, IL-17, Th17",
author = "Utako Fujii and Nobuaki Miyahara and Akihiko Taniguchi and Koichi Waseda and Daisuke Morichika and Etsuko Kurimoto and Hikari Koga and Mikio Kataoka and Gelfand, {Erwin W.} and Cua, {Daniel J.} and Akihiko Yoshimura and Mitsune Tanimoto and Arihiko Kanehiro",
year = "2016",
month = "11",
day = "1",
doi = "10.1165/rcmb.2016-0015OC",
language = "English",
volume = "55",
pages = "697--707",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "5",

}

TY - JOUR

T1 - IL-23 Is essential for the development of Elastase-induced pulmonary inflammation and emphysema

AU - Fujii, Utako

AU - Miyahara, Nobuaki

AU - Taniguchi, Akihiko

AU - Waseda, Koichi

AU - Morichika, Daisuke

AU - Kurimoto, Etsuko

AU - Koga, Hikari

AU - Kataoka, Mikio

AU - Gelfand, Erwin W.

AU - Cua, Daniel J.

AU - Yoshimura, Akihiko

AU - Tanimoto, Mitsune

AU - Kanehiro, Arihiko

PY - 2016/11/1

Y1 - 2016/11/1

N2 - We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-232/2) and wild-Type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-232/2 mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid ofWTmice was attenuated in IL-232/2 mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.

AB - We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-232/2) and wild-Type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-232/2 mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid ofWTmice was attenuated in IL-232/2 mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.

KW - Chronic obstructive pulmonary disease

KW - IL-17

KW - Th17

UR - http://www.scopus.com/inward/record.url?scp=84994430030&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994430030&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2016-0015OC

DO - 10.1165/rcmb.2016-0015OC

M3 - Article

VL - 55

SP - 697

EP - 707

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 5

ER -