PT  - JOURNAL ARTICLE
AU  - N. Miglino
AU  - M. Roth
AU  - M. Tamm
AU  - P. Borger
TI  - House dust mite extract down-regulates C/EBPα in asthmatic bronchial smooth muscle cells
AID  - 10.1183/09031936.00068010
DP  - 2010 Jan 01
TA  - European Respiratory Journal
PG  - erj00680-2010
4099  - http://erj.ersjournals.com/content/early/2010/11/25/09031936.00068010.short
4100  - http://erj.ersjournals.com/content/early/2010/11/25/09031936.00068010.full
AB  - A reduced translation of CEBPA mRNA was associated with increased proliferation of bronchial smooth muscle (BSM) cells of asthma patients. Here we assessed the effect of HDM-extracts on the cell proliferation ([3H]-thymidine incorporation), inflammation (IL-6 release) and on the upstream translation regulatory proteins of C/EBPα 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 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 (i) upregulated CRT, (ii) activated PAR2, (iii) increased the IL-6 expression and (iv) the proliferation of asthmatic BSM cells. Hence, HDM exposure contributes to inflammation and remodeling by a non-immune 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.