Myeloid differentiation-2 is a potential biomarker for the amplification process of allergic airway sensitization in mice.
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 saline-sensitized 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.
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Daisuke
D
Koyama
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Shuichiro
S
Maruoka
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: gon.yasuhiro@nihon-u.ac.jp.
Yasuhiro
Y
Gon
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Yoshitaka
Y
Shintani
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Tadataka
T
Sekiyama
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hisato
H
Hiranuma
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Sotaro
S
Shikano
Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan.
Kazumichi
K
Kuroda
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Ikuko
I
Takeshita
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Eriko
E
Tsuboi
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Kaori
K
Soda
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Shu
S
Hashimoto
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers; D016000:Cluster Analysis; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007114:Immunization; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051218:Lymphocyte Antigen 96 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D039981:Pyroglyphidae / Q000276:immunology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D000485:Allergens; D015415:Biomarkers; D051218:Lymphocyte Antigen 96; D051197:Toll-Like Receptor 4
Asthma; House dust mite; Microarray analysis; Myeloid differentiation-2; Sensitization