| First Author | Fujii U | Year | 2016 |
| Journal | Am J Respir Cell Mol Biol | Volume | 55 |
| Issue | 5 | Pages | 697-707 |
| PubMed ID | 27351934 | Mgi Jnum | J:251227 |
| Mgi Id | MGI:6101259 | Doi | 10.1165/rcmb.2016-0015OC |
| Citation | Fujii U, et al. (2016) IL-23 Is Essential for the Development of Elastase-Induced Pulmonary Inflammation and Emphysema. Am J Respir Cell Mol Biol 55(5):697-707 |
| abstractText | 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 of WT mice 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. |
