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Simvastatin suppresses RANTES-mediated neutrophilia in poly I:C-induced pneumonia.
MedLine Citation:
PMID:  22835616     Owner:  NLM     Status:  Publisher    
Recently, statins have been shown to have anti-inflammatory effects on lung inflammatory diseases. However, the mechanisms of action of simvastatin in viral pneumonia have yet to be elucidated, although viral infection remains a considerable health threat. In this study, we hypothesized that simvastatin inhibits polyinosinic-polycytidylic acid (poly I:C)-induced airway inflammation, such as regulated on activation normal T cell, expressed and secreted (RANTES) expression and inflammatory cell recruitment.In bronchial cells, the effect of simvastatin on poly I:C-induced RANTES expression and signal transducer and activator of transcription 3 (STAT3)-mediated signal transduction was determined using an enzyme-linked immunosorbent assay (ELISA) and shRNA system. In a poly I:C-induced pneumonia mouse model, immunological changes in the lungs after simvastatin inhalation, such as inflammatory cell recruitment and cytokine/chemokine release, were examined.In poly I:C-stimulated bronchial cells, RANTES secretion was increased by STAT3 activation, and simvastatin suppressed poly I:C-induced STAT3 activation, resulting in inhibition of RANTES expression. In BALB/c mice stimulated with inhaled poly I:C, RANTES expression and neutrophil infiltration into the airway were elevated. However, simvastatin treatment attenuated STAT3 activation, RANTES release, and subsequent neutrophilia in the lungs.These findings suggest that simvastatin inhibits airway inflammation, but there are other mechanisms that need to be fully elucidated.
Chang Seok Lee; Eun Hee Yi; Jin-Ku Lee; Cheolhee Won; Young Ju Lee; Min Kyung Shin; Young Mok Yang; Myung-Hee Chung; Jung Weon Lee; Sang-Hyun Sung; Sang-Kyu Ye
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-26
Journal Detail:
Title:  The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology     Volume:  -     ISSN:  1399-3003     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
103 Daehak-Ro, Chongno-Gu, Seoul, 110-799, Republic of Korea.
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