Immunomodulatory effects of CpG oligodeoxynucleotides on house dust mite-induced airway inflammation in mice.
BACKGROUND
CpG oligodeoxynucleotides (CpG ODNs) are reported to protect against airway eosinophilia and hyperresponsiveness in animal models of asthma. However, little is known about the effects of CpG ODNs on house dust mites, one of the most common environmental allergens, causing allergic asthma. In the present study, we evaluated the immunomodulatory effects of CpG ODNs on the development of house dust mite-induced airway inflammation and remodeling in mice.


METHODS
Mice were instilled with Dermatophagoides farinae (Der f) into the trachea 8 times without any additional adjuvants. 48 h after the final allergen instillation, the airway responsiveness to acetylcholine (Ach) was measured, and bronchoalveolar lavage (BAL) and histopathological examination were carried out. CpG ODNs were instilled into the trachea mixed with Der f at the first allergen instillation.


RESULTS
Repeated instillation of Der f induced increases in airway responsiveness to Ach, the numbers of inflammatory cells, the levels of T-helper type 2 cytokines and transforming growth factor-beta(1) in the BAL fluid. Furthermore, goblet cell hyperplasia, the thickness of the epithelium and subepithelial fibrosis were observed. The simultaneous instillation of CpG ODNs with Der f at the first allergen instillation showed significant inhibition of these parameters dose dependently.


CONCLUSIONS
Our results demonstrate that CpG ODNs have inhibitory effects on Der f-induced airway hyperresponsiveness and eosinophilia, as well as airway remodeling, and that CpG ODNs can be a therapeutic approach for the treatment of house dust mite-induced asthma.
Hirose
Izumi
I
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Tanaka
Hiroyuki
H
Takahashi
Go
G
Wakahara
Keiko
K
Tamari
Mayumi
M
Sakamoto
Tatsuo
T
Kojima
Seiji
S
Inagaki
Naoki
N
Nagai
Hiroichi
H
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D040001:Dermatophagoides farinae / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000382:microbiology / Q000473:pathology / Q000628:therapy; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D011657:Pulmonary Eosinophilia / Q000628:therapy
D000276:Adjuvants, Immunologic; D039741:Antigens, Dermatophagoides; C408982:CPG-oligonucleotide; D016207:Cytokines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides