چکیده (انگلیسی):

Background: Allergic sensitization is a key step in the pathogenesis of asthma. However, little is known
about the molecules that are critical regulators for establishing allergic sensitization of the airway. Thus,
we conducted global gene expression profiling to identify candidate genes and signaling pathways
involved in house dust mite (HDM)-induced allergic sensitization in the murine airway.
Methods: We sensitized and challenged mice with HDM or saline as a control through the airway on days
1 and 8. We evaluated eosinophilia in bronchoalveolar lavage fluid (BALF), airway inflammation, and
mucus production on days 7 and 14. We extracted total RNA from lung tissues of HDM- and salinesensitized
mice on days 7 and 14. Microarray analyses were performed to identify up-regulated genes
in the lungs of HDM-sensitized mice compared to the control mice. Data analyses were performed using
GeneSpring software and gene networks were generated using Ingenuity Pathways Analysis (IPA).
Results: We identified 50 HDM-mediated, stepwise up-regulated genes in response to allergic sensitization
and amplification of allergic airway inflammation. The highest expressed gene was myeloid
differentiation-2 (MD-2), a lipopolysaccharide (LPS)-binding component of Toll-like receptor (TLR) 4
signaling complex. MD-2 protein was expressed in lung vascular endothelial cells and was increased in
the serum of HDM-sensitized mice, but not in the control mice.
Conclusions: Our data suggest MD-2 is a critical regulator of the establishment of allergic airway
sensitization to HDM in mice. Serum MD-2 may represent a potential biomarker for the amplification of
allergic sensitization and allergic inflammation.