Role of lung apolipoprotein A-I in idiopathic pulmonary fibrosis: antiinflammatory and antifibrotic effect on experimental lung injury and fibrosis
- Abstract
- RATIONALE: Idiopathic pulmonary fibrosis (IPF) is caused by alterations in expression of proteins involved in multiple pathways, including matrix deposition, inflammation, injury, and repair. OBJECTIVES: To understand the pathogenic changes in lung protein expression in IPF and to evaluate apolipoprotein (Apo) A-I as a candidate therapeutic molecule. METHODS: Two-dimensional electrophoresis was adopted for differential display proteomics. Reverse-transcriptase polymerase chain reaction, Western blotting, immunohistochemical staining, and ELISA were performed for identification and quantitative measurement of Apo A-I in bronchoalveolar lavage fluids from subjects with IPF and experimental bleomycin-induced mice. MEASUREMENTS AND MAIN RESULTS: Sixteen protein spots showed differences in relative intensity between IPF (n = 14) and healthy control subjects (n = 8). Nano liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed increase of haptoglobulin and decrease of alpha(1)-antitrypsin, alpha(1)-antichymotrypsin, macrophage capping protein, angiotensinogen, hemoglobin chain B, Apo A-I, clusterin, protein disulfide isomerase A3, immunoglobulin, and complement C4A in IPF compared with normal control subjects (P = 0.006-0.044). Apo A-I concentrations were lower in bronchoalveolar lavage fluids from subjects with IPF (n = 28) than in normal control subjects (n = 18; P < 0.01). In bleomycin-treated mice, Apo A-I protein in BALF was lower than that in sham-treated control animals. Immunohistochemical analysis showed positive staining on intraalveolar macrophages and epithelial cells of the lungs. Intranasal treatment with Apo A-I protein reduced the bleomycin-induced increases in number of inflammatory cells and collagen deposition in sham-treated mice in a dose-dependent manner. CONCLUSIONS: Alterations of several inflammatory and antiinflammatory proteins in the lungs may be related to the pathogenesis of IPF, and local treatment with Apo A-I is very effective against the development of experimental lung injury and fibrosis.
- All Author(s)
- T. H. Kim
; Y. H. Lee
; K. H. Kim
; S. H. Lee
; J. Y. Cha
; E. K. Shin
; S. Jung
; A. S. Jang
; S. W. Park
; S. T. Uh
; Y. H. Kim
; J. S. Park
; H. G. Sin
; W. Youm
; E. S. Koh
; S. Y. Cho
; Y. K. Paik
; T. Y. Rhim
; C. S. Park
- Issued Date
- 2010
- Type
- Article
- Keyword
- fibrosis, pulmonary; idiopathic interstitial pneumonia; apolipoprotein A-I; bleomycin A2
- Publisher
- American Thoracic Society
American Lung Association
- ISSN
- 1073-449x
- Citation Title
- American Journal of Respiratory and Critical Care Medicine
- Citation Volume
- 182
- Citation Number
- 5
- Citation Start Page
- 633
- Citation End Page
- 642
- Language(ISO)
- eng
- DOI
- 10.1164/rccm.200905-0659OC
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/1205
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