Preventive effect of galectin-9 on double-stranded RNA-induced airway hyperresponsiveness in an exacerbation model of mite antigen-induced asthma in mice.
BACKGROUND
Viral respiratory infection is the most common cause of acute asthma exacerbation in patients with stable asthma. The replication of most respiratory viruses requires the generation of double-stranded RNA (dsRNA), resulting in the activation of host immune responses. Synthetic dsRNA, polyinosinic-polycytidylic acid (PolyIC), mimics the effects of viruses in various cell types. To evaluate new therapies for mite antigen-induced chronic asthma, we developed an acute exacerbation model of mouse chronic asthma using mite antigen and PolyIC. We also examined the preventive effects of recombinant galectin-9 (Gal-9) on acute asthma exacerbation in this model.


METHODS
Airway hyperresponsiveness (AHR) was examined to evaluate the exacerbation of chronic asthma. To analyze airway inflammation, the numbers of inflammatory cells and concentrations of cytokines in the bronchoalveolar lavage fluid (BALF) were estimated by flow cytometry and enzyme-linked immunosorbent assay, respectively.


RESULTS
AHR was accelerated by intranasal administration of PolyIC in addition to mite antigen. Levels of cytokines that contribute to AHR, including interferon-γ, tumor necrosis factor-α, and RANTES (CCR5), and of Gal-9 in the BALF were elevated in this acute asthma exacerbation mouse model. Intranasal administration of recombinant Gal-9 reduced the PolyIC-induced AHR and levels of these cytokines in the BALF. Further, Gal-9 suppressed the production of cytokines induced by PolyIC in the alveolar macrophages. CONCLUSIONS. Our findings demonstrated that exogenous Gal-9 suppressed dsRNA-induced AHR in an acute exacerbation model of chronic asthma in mice, and suggest that recombinant Gal-9 could be therapeutically effective for preventing acute asthma exacerbation.
1Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan.
Shigeki
S
Katoh
Hiroki
H
Shimizu
Yasushi
Y
Obase
Souichi
S
Oomizu
Toshiro
T
Niki
Masaki
M
Ikeda
Keiji
K
Mouri
Yoshihiro
Y
Kobashi
Mistuomi
M
Hirashima
Mikio
M
Oka
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D037161:Galectins / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011070:Poly I-C / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control
D000485:Allergens; D039741:Antigens, Dermatophagoides; D018925:Chemokines; D016207:Cytokines; D037161:Galectins; C105032:LGALS9 protein, human; D011994:Recombinant Proteins; D011070:Poly I-C