2016年11月
IL-23 Is Essential for the Development of Elastase-Induced Pulmonary Inflammation and Emphysema
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
- 巻
- 55
- 号
- 5
- 開始ページ
- 697
- 終了ページ
- 707
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1165/rcmb.2016-0015OC
- 出版者・発行元
- AMER THORACIC SOC
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-23(-/-)) 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-23(-/-) 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-23(-/-) 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.
- リンク情報
- ID情報
-
- DOI : 10.1165/rcmb.2016-0015OC
- ISSN : 1044-1549
- eISSN : 1535-4989
- PubMed ID : 27351934
- Web of Science ID : WOS:000387327300009