title: Role of lung apolipoprotein A-I in idiopathic pulmonary fibrosis: antiinflammatory and antifibrotic effect on experimental lung injury and fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is caused by alterations in expression of proteins involved in multiple pathways, including matrix deposition, inflammation, injury, and repair.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University, Bucheon Hospital, 1174 Jung-Dong, Wonmi-Ku, Bucheon, Kyeonggi-Do, South Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Yoo Hoon
authors.initials: YH
authors.lastname: Lee
authors.forename: Kyung Hun
authors.initials: KH
authors.lastname: Kim
authors.forename: Shin Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Cha
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Shin
authors.forename: Seok
authors.initials: S
authors.lastname: Jung
authors.forename: An Soo
authors.initials: AS
authors.lastname: Jang
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Soo Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Jai Soung
authors.initials: JS
authors.lastname: Park
authors.forename: Hwa Gyoun
authors.initials: HG
authors.lastname: Sin
authors.forename: Wook
authors.initials: W
authors.lastname: Youm
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Koh
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Cho
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Paik
authors.forename: Tai Youn
authors.initials: TY
authors.lastname: Rhim
authors.forename: Choon Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000368:Aged; D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D001761:Bleomycin; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D040901:Proteomics / Q000379:methods; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016632:Apolipoprotein A-I; D012333:RNA, Messenger; D001761:Bleomycin