Bleomycin-induced pulmonary fibrosis is attenuated by anti-KL-6 antibody
XU Ling, YANG Dan-rong, ZHU Song-lei, GU Jie, DING Feng-ming, BIAN Wei, RONG Zhao-hui
Published 2013-11-20
Cite as Int J Respir, 2013,33(22): 1714-1720,封3. DOI: 10.3760/cma.j.issn.1673-436x.2013.022.009
Abstract
Objective To assess the effect and mechanisms of anti-KL-6 antibody on bleomycininduced pulmonary fibrosis in mice.Methods Pulmonary fibrosis was induced in C57BL/6 mice by intratracheal instillation of bleomycin.Anti-KL-6 antibody was given from two days before bleomycin instillation to the 21st day after bleomycin instillation.Lung inflammation was assessed by bronchoalveolar lavage fluid (BALF) differential cell count.Changes in tissue remodeling were evaluated by quantified pathological examination,measurement of hydroxyproline content.Collagen type Ⅰ and type Ⅲ were detected by qRT-PCR,KL-6,transforming growth factor-β1 (TGF-β1),and hepatocyte growth factor (HGF) in lung tissues were detected by ELISA,and epithelial apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining.Results Anti-KL-6 antibody significantly reduced the number of alveolar inflammatory cells,macrophages and lymphocytes in BALF on the 21st day after bleomycin instillation (P ＜0.05).On the 14th and 21st day,the histopathological changes of pulmonary fibrosis were attenuated and the increase of lung hydroxyproline content and collagen (type Ⅰ and type Ⅲ) mRNA expression induced by bleomycin were alleviated (P ＜0.05).Moreover,anti-KL 6 antibody down-regulated the increased production of TGF-β1 and KL-6 and up-regulated the decreased production of HGF induced by bleomycin (P ＜0.05).Epithelial apoptosis was also reduced by anti KL-6 antibody (P ＜ 0.05).Conclusions Anti-KL 6 antibody attenuates bleomycin-induced pulmonary fibrosis,possibly through reducing the expression of collagen type Ⅰ and type Ⅲ,increasing HGF level,attenuating the production of KL-6 and TGF-β1,and alleviating epithelial apoptosis.
Key words:
Pulmonary fibrosis; KL-6; Transforming growth factor β1 ; Hepatocyte growth factor; Apoptosis
Contributor Information
XU Ling
Department of Respiratory Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233 ,China
YANG Dan-rong
Department of Respiratory Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233 ,China
ZHU Song-lei
Department of Respiratory Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233 ,China
GU Jie
Department of Respiratory Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233 ,China
DING Feng-ming
Department of Respiratory Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233 ,China
BIAN Wei
Department of Respiratory Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233 ,China
RONG Zhao-hui
Department of Respiratory Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233 ,China
