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-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.
authors.affiliation: 1 Department of Hematology, Oncology, Allergy and Respiratory Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and.
authors.forename: Utako
authors.initials: U
authors.lastname: Fujii
authors.affiliation: 1 Department of Hematology, Oncology, Allergy and Respiratory Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and.|2 Field of Medical Technology, Graduate School of Health Sciences, Okayama University, Okayama, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Miyahara
authors.affiliation: 1 Department of Hematology, Oncology, Allergy and Respiratory Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Taniguchi
authors.affiliation: 1 Department of Hematology, Oncology, Allergy and Respiratory Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and.
authors.forename: Koichi
authors.initials: K
authors.lastname: Waseda
authors.affiliation: 1 Department of Hematology, Oncology, Allergy and Respiratory Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morichika
authors.affiliation: 1 Department of Hematology, Oncology, Allergy and Respiratory Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Kurimoto
authors.affiliation: 1 Department of Hematology, Oncology, Allergy and Respiratory Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and.
authors.forename: Hikari
authors.initials: H
authors.lastname: Koga
authors.affiliation: 1 Department of Hematology, Oncology, Allergy and Respiratory Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and.|2 Field of Medical Technology, Graduate School of Health Sciences, Okayama University, Okayama, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Kataoka
authors.affiliation: 3 Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado.
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
authors.affiliation: 4 Merck Research Laboratory, Palo Alto, California; and.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cua
authors.affiliation: 5 Department of Biochemistry and Molecular Vascular Biology, Keio University Graduate School of Medical Science, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: 1 Department of Hematology, Oncology, Allergy and Respiratory Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and.
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.affiliation: 1 Department of Hematology, Oncology, Allergy and Respiratory Medicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and.
authors.forename: Arihiko
authors.initials: A
authors.lastname: Kanehiro
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D018450:Disease Progression; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000172:deficiency / Q000378:metabolism*; D007700:Kinetics; D008168:Lung / Q000473:pathology; D018655:Lymphocyte Count; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase; D011014:Pneumonia / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D034421:Sus scrofa
chemical_list: D000911:Antibodies, Monoclonal; D018925:Chemokines; D020381:Interleukin-17; D053759:Interleukin-23; D007371:Interferon-gamma; D010196:Pancreatic Elastase
keywords: IL-17; Th17; chronic obstructive pulmonary disease