title: Bleomycin-induced pulmonary fibrosis is attenuated by an antibody against KL-6.
abstract: BACKGROUND
  Elevated levels of KL-6 are reported in the serum and/or bronchoalveolar lavage fluid (BALF) of patients with interstitial lung disease (ILD) and are useful to estimate the severity and prognosis of the disease. However, whether the anti-KL-6 antibody could attenuate pulmonary fibrosis remains unclear.
  
  
  OBJECTIVE
  This study aims to investigate the therapeutic effects and mechanisms of anti-KL-6 antibody on bleomycin-induced pulmonary fibrosis.
  
  
  METHODS
  A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (5 mg/kg). Mouse received anti-KL-6 antibody (20 ug/day, once a day) from day 7 to 21 after bleomycin injection. The effects of anti-KL-6 antibody were evaluated by pathological examination, measuring hydroxyproline measurements in lung tissues, leukocyte counts in BALF and the expression of collagen type I and type III using qRT-PCR. The expression of profibrotic cytokine (transforming growth factor-β1, TGF-β1), antifibrotic cytokine (hepatocyte growth factor, HGF), and KL-6 in lung tissues were analyzed by ELISA. The apoptosis of epithelial cell was examined by TUNEL staining.
  
  
  RESULTS
  Anti-KL-6 antibody significantly reduced the number of alveolar inflammatory leukocytes (total and differential counts) in BALF of mice with bleomycin-induced pulmonary fibrosis as well as the content of hydroxyproline in the lung tissues. Treatment with anti-KL-6 antibody downregulated the expression of collagen type I, TGF-β1 and KL-6, upregulated the expression of HGF and inhibited the apoptosis of epithelial cells.
  
  
  CONCLUSIONS
  These findings indicated the anti-KL-6 antibody may potentially be developed as a useful inhibitor of pulmonary fibrosis.
authors.affiliation: Department of Respiratory Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China. lingxu813@163.com
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Danrong
authors.initials: D
authors.lastname: Yang
authors.forename: Songlei
authors.initials: S
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Gu
authors.forename: Fengming
authors.initials: F
authors.lastname: Ding
authors.forename: Wei
authors.initials: W
authors.lastname: Bian
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Rong
authors.forename: Ce
authors.initials: C
authors.lastname: Shen
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000276:immunology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D013047:Specific Pathogen-Free Organisms
chemical_list: D000911:Antibodies, Monoclonal; D024042:Collagen Type I; D024061:Collagen Type III; D016207:Cytokines; C060192:MUC1 protein, human; D018396:Mucin-1; D001761:Bleomycin; D006909:Hydroxyproline