Role of lung apolipoprotein A-I in idiopathic pulmonary fibrosis: Antiinflammatory and antifibrotic effect on experimental lung injury and fibrosis

Tae Hoon Kim, Yoo Hoon Lee, Kyung Hun Kim, Shin Hwa Lee, Ji Yeon Cha, Eun Kyoung Shin, Seok Jung, An Soo Jang, Sung Woo Park, Soo Taek Uh, Young Hoon Kim, Jai Soung Park, Hwa Gyoun Sin, Wook Youm, Eun Suk Koh, Sun Young Cho, Young Ki Paik, Tai Youn Rhim, Choon Sik Park

Research output: Contribution to journalArticle

57 Citations (Scopus)

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 α1-antitrypsin, α1-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 adose-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.

Original languageEnglish
Pages (from-to)633-642
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume182
Issue number5
DOIs
Publication statusPublished - 2010 Sep 1

Fingerprint

Idiopathic Pulmonary Fibrosis
Apolipoprotein A-I
Lung Injury
Fibrosis
Anti-Inflammatory Agents
Lung
Proteins
Bleomycin
Bronchoalveolar Lavage Fluid
Macrophages
Clusterin
Staining and Labeling
Protein Disulfide-Isomerases
Angiotensinogen
Tandem Mass Spectrometry
Reverse Transcriptase Polymerase Chain Reaction
Liquid Chromatography
Proteomics
Electrophoresis
Immunoglobulins

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Kim, Tae Hoon ; Lee, Yoo Hoon ; Kim, Kyung Hun ; Lee, Shin Hwa ; Cha, Ji Yeon ; Shin, Eun Kyoung ; Jung, Seok ; Jang, An Soo ; Park, Sung Woo ; Uh, Soo Taek ; Kim, Young Hoon ; Park, Jai Soung ; Sin, Hwa Gyoun ; Youm, Wook ; Koh, Eun Suk ; Cho, Sun Young ; Paik, Young Ki ; Rhim, Tai Youn ; Park, Choon Sik. / Role of lung apolipoprotein A-I in idiopathic pulmonary fibrosis : Antiinflammatory and antifibrotic effect on experimental lung injury and fibrosis. In: American Journal of Respiratory and Critical Care Medicine. 2010 ; Vol. 182, No. 5. pp. 633-642.
@article{9e9e654d4016457784019e8434abaf84,
title = "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 α1-antitrypsin, α1-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 adose-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.",
author = "Kim, {Tae Hoon} and Lee, {Yoo Hoon} and Kim, {Kyung Hun} and Lee, {Shin Hwa} and Cha, {Ji Yeon} and Shin, {Eun Kyoung} and Seok Jung and Jang, {An Soo} and Park, {Sung Woo} and Uh, {Soo Taek} and Kim, {Young Hoon} and Park, {Jai Soung} and Sin, {Hwa Gyoun} and Wook Youm and Koh, {Eun Suk} and Cho, {Sun Young} and Paik, {Young Ki} and Rhim, {Tai Youn} and Park, {Choon Sik}",
year = "2010",
month = "9",
day = "1",
doi = "10.1164/rccm.200905-0659OC",
language = "English",
volume = "182",
pages = "633--642",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "5",

}

Kim, TH, Lee, YH, Kim, KH, Lee, SH, Cha, JY, Shin, EK, Jung, S, Jang, AS, Park, SW, Uh, ST, Kim, YH, Park, JS, Sin, HG, Youm, W, Koh, ES, Cho, SY, Paik, YK, Rhim, TY & Park, CS 2010, 'Role of lung apolipoprotein A-I in idiopathic pulmonary fibrosis: Antiinflammatory and antifibrotic effect on experimental lung injury and fibrosis', American Journal of Respiratory and Critical Care Medicine, vol. 182, no. 5, pp. 633-642. https://doi.org/10.1164/rccm.200905-0659OC

Role of lung apolipoprotein A-I in idiopathic pulmonary fibrosis : Antiinflammatory and antifibrotic effect on experimental lung injury and fibrosis. / Kim, Tae Hoon; Lee, Yoo Hoon; Kim, Kyung Hun; Lee, Shin Hwa; Cha, Ji Yeon; Shin, Eun Kyoung; Jung, Seok; Jang, An Soo; Park, Sung Woo; Uh, Soo Taek; Kim, Young Hoon; Park, Jai Soung; Sin, Hwa Gyoun; Youm, Wook; Koh, Eun Suk; Cho, Sun Young; Paik, Young Ki; Rhim, Tai Youn; Park, Choon Sik.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 182, No. 5, 01.09.2010, p. 633-642.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of lung apolipoprotein A-I in idiopathic pulmonary fibrosis

T2 - Antiinflammatory and antifibrotic effect on experimental lung injury and fibrosis

AU - Kim, Tae Hoon

AU - Lee, Yoo Hoon

AU - Kim, Kyung Hun

AU - Lee, Shin Hwa

AU - Cha, Ji Yeon

AU - Shin, Eun Kyoung

AU - Jung, Seok

AU - Jang, An Soo

AU - Park, Sung Woo

AU - Uh, Soo Taek

AU - Kim, Young Hoon

AU - Park, Jai Soung

AU - Sin, Hwa Gyoun

AU - Youm, Wook

AU - Koh, Eun Suk

AU - Cho, Sun Young

AU - Paik, Young Ki

AU - Rhim, Tai Youn

AU - Park, Choon Sik

PY - 2010/9/1

Y1 - 2010/9/1

N2 - 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 α1-antitrypsin, α1-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 adose-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.

AB - 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 α1-antitrypsin, α1-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 adose-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.

UR - http://www.scopus.com/inward/record.url?scp=77957705241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957705241&partnerID=8YFLogxK

U2 - 10.1164/rccm.200905-0659OC

DO - 10.1164/rccm.200905-0659OC

M3 - Article

C2 - 20463180

AN - SCOPUS:77957705241

VL - 182

SP - 633

EP - 642

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 5

ER -