Document Detail

Suppression of discoidin domain receptor 1 by RNA interference attenuates lung inflammation.
MedLine Citation:
PMID:  16424224     Owner:  NLM     Status:  MEDLINE    
Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase whose ligand is collagen. Recently, we have reported the association of DDR1 in the cytokine production of human leukocytes in in vitro and in vivo expression in idiopathic pulmonary fibrosis. However, its role in in vivo inflammation has not been fully elucidated. Small interference RNA (siRNA) can induce specific suppression of in vitro and in vivo gene expression. In this study, using a bleomycin-induced pulmonary fibrosis mouse model, we administered siRNA against DDR1 transnasally and evaluated histological changes, cytokine expression, and signaling molecule activation in the lungs. Histologically, siRNA against DDR1 successfully reduced in vivo DDR1 expression and attenuated bleomycin-induced infiltration of inflammatory cells. Furthermore, it significantly reduced inflammatory cell counts and concentrations of cytokines such as MCP-1, MIP-1alpha, and MIP-2 in bronchoalveolar lavage fluid. Subsequently, bleomycin-induced up-regulation of TGF-beta in bronchoalveolar lavage fluid was significantly inhibited, and collagen deposition in the lungs was reduced. Furthermore, siRNA against DDR1 significantly inhibited bleomycin-induced P38 MAPK activation in the lungs. Considered together, we propose that DDR1 contributes to the development of bleomycin-induced pulmonary inflammation and fibrosis.
Wataru Matsuyama; Masaki Watanabe; Yuko Shirahama; Ryuki Hirano; Hideo Mitsuyama; Ikkou Higashimoto; Mistuhiro Osame; Kimiyoshi Arimura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Retracted Publication    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  176     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-20     Completed Date:  2006-03-24     Revised Date:  2012-06-01    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1928-36     Citation Subset:  AIM; IM    
Division of Respiratory Medicine, Respiratory and Stress Care Center, Kagoshima University Hospital, Kagoshima, Japan.
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MeSH Terms
Administration, Intranasal
Bleomycin / toxicity
Bronchoalveolar Lavage Fluid / cytology
Cells, Cultured
Cytokines / biosynthesis,  genetics
Mice, Inbred C57BL
Protein Structure, Tertiary
Pulmonary Fibrosis / chemically induced,  immunology*,  pathology
RNA, Small Interfering / administration & dosage*
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*,  biosynthesis,  genetics*
Receptors, Mitogen / antagonists & inhibitors*,  biosynthesis,  genetics*
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Reg. No./Substance:
0/Cytokines; 0/RNA, Small Interfering; 0/Receptors, Mitogen; 11056-06-7/Bleomycin; EC Protein-Tyrosine Kinases; EC receptor; EC Mitogen-Activated Protein Kinases
Retraction In:
Watanabe M, Shirahama Y, Hirano R, Mitsuyama H, Higashimoto I, Osame M, Arimura K. J Immunol. 2008 Nov 1;181(9):6671   [PMID:  18941259 ]

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