title: Establishment of the mouse model of acute exacerbation of idiopathic pulmonary fibrosis.
abstract: OBJECTIVE
  To explore and establish an animal model of AE-IPF.
  
  
  METHODS
  An animal model of idiopathic pulmonary fibrosis (IPF) was established using bleomycin (BLM). Then, BLM was administered a second time on day 21 to induce AE-IPF (which mimics human AE-IPF). Evaluation of the success of animal model was based on the survival of mice, as well as assessment of pathological changes in lung tissue. Preliminary investigation into the immunological mechanism of AE-IPF was also explored via the detection and identification of the inflammatory cells in mouse bronchoalveolar lavage fluid (BALF) and the concentrations of six cytokines (IL-4, IL-6, IL-10, IL-17A, MIG, and TGF-β1) in BALF supernatants, which were closely associated with IPF and AE-IPF. The intervention role of IL-17A antibody to AE was explored.
  
  
  RESULTS
  By week 4 after the second BLM administration, the mortality in the AE-IPF group was significantly greater (45%, 9/20) than that in stable-IPF group (0/18) (P = .0017). The average body weight in AE-IPF group was significantly lower than that in stable group (P < .0001). In AE-IPF group, inflammation and fibrosis were severer by histopathology analysis. In BALF, IL-17A, MIG (CXCL-9), IL-6, and TGF-β1 levels in AE group were significantly higher. The percentages of neutrophils and Th17 cells in BALF were significantly higher in AE group (P < .01; P = .0281). IL-17A antibody could attenuated the lung inflammation induced by twice BLM challenges.
  
  
  CONCLUSIONS
  A mouse model of AE-IPF can be established using two administrations of BLM; Th17 cells may play a key role during the pathological process of AE-IPF.
authors.affiliation: a Department of Respiratory Medicine, Shanghai Pulmonary Hospital , Tongji University, School of Medicine , Shanghai , China.
authors.forename: Ya-Ru
authors.initials: YR
authors.lastname: Wei
authors.affiliation: a Department of Respiratory Medicine, Shanghai Pulmonary Hospital , Tongji University, School of Medicine , Shanghai , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qiu
authors.affiliation: a Department of Respiratory Medicine, Shanghai Pulmonary Hospital , Tongji University, School of Medicine , Shanghai , China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: a Department of Respiratory Medicine, Shanghai Pulmonary Hospital , Tongji University, School of Medicine , Shanghai , China.
authors.forename: Yu-Kui
authors.initials: YK
authors.lastname: Du
authors.affiliation: a Department of Respiratory Medicine, Shanghai Pulmonary Hospital , Tongji University, School of Medicine , Shanghai , China.
authors.forename: Zhao-Fang
authors.initials: ZF
authors.lastname: Yin
authors.affiliation: a Department of Respiratory Medicine, Shanghai Pulmonary Hospital , Tongji University, School of Medicine , Shanghai , China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Chen
authors.affiliation: a Department of Respiratory Medicine, Shanghai Pulmonary Hospital , Tongji University, School of Medicine , Shanghai , China.
authors.forename: Yue-Ping
authors.initials: YP
authors.lastname: Jin
authors.affiliation: a Department of Respiratory Medicine, Shanghai Pulmonary Hospital , Tongji University, School of Medicine , Shanghai , China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Zhao
authors.affiliation: b State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences , Chinese Academy of Sciences , Shanghai , China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: a Department of Respiratory Medicine, Shanghai Pulmonary Hospital , Tongji University, School of Medicine , Shanghai , China.
authors.forename: Dong
authors.initials: D
authors.lastname: Weng
authors.affiliation: a Department of Respiratory Medicine, Shanghai Pulmonary Hospital , Tongji University, School of Medicine , Shanghai , China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Li
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D054370:Chemokine CXCL9 / Q000378:metabolism; D004195:Disease Models, Animal; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D054370:Chemokine CXCL9; D020381:Interleukin-17; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D016753:Interleukin-10; D015847:Interleukin-4
keywords: acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF); bleomycin; mouse model