Document Detail


House dust mite extract downregulates C/EBPα in asthmatic bronchial smooth muscle cells.
MedLine Citation:
PMID:  21109558     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Reduced translation of CEBPA mRNA has been associated with increased proliferation of bronchial smooth muscle (BSM) cells of asthma patients. Here, we assessed the effect of house dust mite (HDM) extracts on the cell proliferation ([(3)H]-thymidine incorporation), inflammation (interleukin (IL)-6 release) and upstream translation regulatory proteins of CCAAT/enhancer-binding protein (C/EBP)α in human BSM cells of healthy controls and asthmatic patients. HDM extract significantly increased IL-6 protein and proliferation of BSM cells of asthma patients only. HDM extract reduced the C/EBPα expression in BSM cells of asthma patients, which coincided with significantly increased levels of calreticulin (CRT) protein, an inhibitor of CEBPA mRNA translation. HDM extract elicited both protease-dependent and -independent responses, which were mediated via protease-activated receptor (PAR)2 and CRT, respectively. In conclusion, HDM extract reduced CEBPA mRNA translation, specifically in asthmatic BSM cells, and 1) upregulated CRT, 2) activated PAR2, and increased 3) IL-6 expression and 4) the proliferation of asthmatic BSM cells. Hence, HDM exposure contributes to inflammation and remodelling by a nonimmune cell-mediated mechanism via a direct interaction with BSM cells. These findings may potentially explain several pathological features of this disease, in particular BSM cell hyperplasia.
Authors:
N Miglino; M Roth; M Tamm; P Borger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-25
Journal Detail:
Title:  The European respiratory journal     Volume:  38     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-01     Completed Date:  2012-01-23     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  50-8     Citation Subset:  IM    
Affiliation:
Pulmonary Cell Research, Dept of Biomedicine, Pneumology, University Hospital Basel, Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Asthma / metabolism*
Bronchi / metabolism*
CCAAT-Enhancer-Binding Protein-alpha / metabolism*
Calreticulin / biosynthesis
Cell Proliferation
Cell Survival
Dermatophagoides pteronyssinus / metabolism
Down-Regulation
Enzyme-Linked Immunosorbent Assay / methods
Gene Expression Regulation*
Humans
Interleukin-6 / biosynthesis
Myocytes, Smooth Muscle / metabolism*
RNA, Small Interfering / metabolism
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Protein-alpha; 0/Calreticulin; 0/Interleukin-6; 0/RNA, Small Interfering
Comments/Corrections
Comment In:
Eur Respir J. 2011 Jul;38(1):4-6   [PMID:  21719495 ]

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