Document Detail


The calpain inhibitor calpeptin prevents bleomycin-induced pulmonary fibrosis in mice.
MedLine Citation:
PMID:  20846163     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pulmonary fibrosis is characterized by progressive worsening of pulmonary function leading to a high incidence of death. Currently, however, there has been little progress in therapeutic strategies for pulmonary fibrosis. There have been several reports on cytokines being associated with lung fibrosis, including interleukin (IL)-6 and transforming growth factor (TGF)-β1. We reported recently that two substances (ATRA and thalidomide) have preventive effects on pulmonary fibrosis by inhibiting IL-6-dependent proliferation and TGF-β1-dependent transdifferentiation of lung fibroblasts. Rheumatoid arthritis is a chronic autoimmune disorder, and its pathogenesis is also characterized by an association with several cytokines. It has been reported that calpain, a calcium-dependent intracellular cysteine protease, plays an important role in the progression of rheumatoid arthritis. In this study, we examined the preventive effect of Calpeptin, a calpain inhibitor, on bleomycin-induced pulmonary fibrosis. We performed histological examinations and quantitative measurements of IL-6, TGF-β1, collagen type Iα1 and angiopoietin-1 in bleomycin-treated mouse lung tissues with or without the administration of Calpeptin. Calpeptin histologically ameliorated bleomycin-induced pulmonary fibrosis in mice. Calpeptin decreased the expression of IL-6, TGF-β1, angiopoietin-1 and collagen type Iα1 mRNA in mouse lung tissues. In vitro studies disclosed that Calpeptin reduced (i) production of IL-6, TGF-β1, angiopoietin-1 and collagen synthesis from lung fibroblasts; and (ii) both IL-6-dependent proliferation and angiopoietin-1-dependent migration of the cells, which could be the mechanism underlying the preventive effect of Calpeptin on pulmonary fibrosis. These data suggest the clinical use of Calpeptin for the prevention of pulmonary fibrosis.
Authors:
C Tabata; R Tabata; T Nakano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-15
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  162     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-12     Completed Date:  2011-03-08     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  560-7     Citation Subset:  IM    
Copyright Information:
© 2010 Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.
Affiliation:
Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. ctabata@hyo-med.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Angiopoietin-1 / genetics,  metabolism
Animals
Bleomycin / administration & dosage
Calpain / antagonists & inhibitors
Cell Line, Transformed
Cell Movement / drug effects
Cell Proliferation / drug effects
Collagen Type I / biosynthesis,  genetics
Dipeptides / administration & dosage*,  pharmacology
Female
Fibroblasts / drug effects*,  immunology,  metabolism,  pathology
Humans
Interleukin-6 / genetics,  metabolism
Lung / drug effects*,  immunology,  metabolism,  pathology
Mice
Mice, Inbred C57BL
Pulmonary Fibrosis / chemically induced,  drug therapy*,  immunology,  physiopathology
Transforming Growth Factor beta1 / biosynthesis,  genetics
Chemical
Reg. No./Substance:
0/Angiopoietin-1; 0/Collagen Type I; 0/Dipeptides; 0/Interleukin-6; 0/Transforming Growth Factor beta1; 11056-06-7/Bleomycin; 117591-20-5/calpeptin; EC 3.4.22.-/Calpain
Comments/Corrections

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