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

研究成果: Article

11 引用 (Scopus)

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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.

元の言語English
ページ(範囲)697-707
ページ数11
ジャーナルAmerican Journal of Respiratory Cell and Molecular Biology
55
発行部数5
DOI
出版物ステータスPublished - 2016 11 1

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ASJC Scopus subject areas

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

これを引用

Fujii, U., Miyahara, N., Taniguchi, A., Waseda, K., Morichika, D., Kurimoto, E., Koga, H., Kataoka, M., Gelfand, E. W., Cua, D. J., 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, 55(5), 697-707. https://doi.org/10.1165/rcmb.2016-0015OC