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

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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

All Science Journal Classification (ASJC) codes

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

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    Kim, T. H., Lee, Y. H., Kim, K. H., Lee, S. H., Cha, J. Y., Shin, E. K., Jung, S., Jang, A. S., Park, S. W., Uh, S. T., Kim, Y. H., Park, J. S., Sin, H. G., Youm, W., Koh, E. S., Cho, S. Y., Paik, Y. K., Rhim, T. Y., & Park, C. S. (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, 182(5), 633-642. https://doi.org/10.1164/rccm.200905-0659OC