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 ([3H]-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.
- bronchial smooth muscle cells
- CCAAT/enhancer-binding protein α
- house dust mite extract
- mRNA translation
For editorial comments see page 4.
The study was supported by the Swiss National Foundation (grant number SNF320000-116022), the Nora van Meeuven-Häfliger Stiftung and the Novartis Research Foundation.
Statement of Interest
A statement of interest for this study can be found at www.erj.ersjournals.com/site/misc/statements.xhtml
- Received April 30, 2010.
- Accepted October 18, 2010.
- ©ERS 2011