Repeated instillations of Dermatophagoides farinae into the airways can induce Th2-dependent airway hyperresponsiveness, eosinophilia and remodeling in mice: effect of intratracheal treatment of fluticasone propionate.
Dermatophagoides farinae are known to be a common environmental allergen causing allergic asthma; however, little is known about their pathophysiological effect via the allergenicities in vivo. Therefore, we first established a mouse model of asthma induced by repeated instillations of D. farinae. Second, to investigate whether the asthmatic responses are Th2-dependent, we examined the effect of the deficiency of interleukin-4 (IL-4) receptor alpha chain gene. Finally, we examined the effect of fluticasone propionate on this model. Mice were instilled with D. farinae without additional adjuvants into the trachea 8 times. After the final allergen instillation, the airway responsiveness to acetylcholine was measured, and bronchoalveolar lavage and histological examination were carried out. The instillation of the allergen-induced airway hyperresponsiveness, the accumulation of inflammatory cells and increases in the levels of Th2 cytokines and transforming growth factor-beta(1) production in the bronchoalveolar lavage fluid dose dependently. The number of goblet cells in the epithelium and the extent of the fibrotic area beneath the basement membrane were also increased in the morphometric study. In contrast, the defect of IL-4/IL-13 signaling through IL-4 receptor alpha chain completely abrogated all these responses. Furthermore, the simultaneous instillation of fluticasone propionate with the allergen showed significant inhibition or an inhibitory tendency of these changes. These findings demonstrate that the repetitive intratracheal instillations of D. farinae can induce airway remodeling through Th2-type inflammation, and that fluticasone propionate inhibits D. farinae-induced airway remodeling in mice, and this model would be useful for studying mechanisms involved in the development of allergic asthma.
Wakahara
Keiko
K
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Tanaka
Hiroyuki
H
Takahashi
Go
G
Tamari
Mayumi
M
Nasu
Reishi
R
Toyohara
Tatsuyuki
T
Takano
Hirohisa
H
Saito
Saburo
S
Inagaki
Naoki
N
Shimokata
Kaoru
K
Nagai
Hiroichi
H
D000109:Acetylcholine / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D040001:Dermatophagoides farinae / Q000276:immunology*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000378:metabolism; D000068298:Fluticasone; D020397:Goblet Cells / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D000068298:Fluticasone; D000109:Acetylcholine