Masahide Takeda, MD, PhD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Wataru Ito, MD, PhD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Shigeharu Ueki, MD, PhD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Hiroyuki Hirasawa, PhD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Miyoshi Fujita, PhD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Yasunori Konno
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Mami Chihara, MD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Masamichi Itoga, MD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Yuki Moritoki, MD, PhD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Yoshiki Kobayashi, MD, PhD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Hiroyuki Kayaba, MD, PhD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Junichi Chihara, MD, PhD
,
Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
Background: Epidemiological studies have already shown that females are dominant in terms of the sex ratio of adult asthma prevalence and severe asthma. It has also been reported that female mice are more susceptible to the development of allergic airway inflammation and airway hyperresponsiveness(AHR) than males. However, there have been few reports of studies on sex difference in the pathogenesis of severe asthma, especially airway remodeling in an animal model. In this study, we investigated sex difference in formation of airway remodeling using a long-term antigen challenged asthma model.
Methods: Following ovalbumin (OVA)/alum intraperitoneal injection, male or female mice (BALB/c) were challenged with aerosolized 1% OVA on 3 days/week for 5 weeks, and we investigated the sex difference in AHR, airway inflammation, as well as airway remodeling.
Results: In OVA-sensitized and -challenged (OVA/OVA) female mice, AHR, the number of eosinophils and lymphocytes, as well as Th2 cytokines and growth factors in BAL fluid were increased compared with OVA/OVA male mice. On the other hand, there is no significant difference in the level of eotaxin in BAL fluid. The histological features of airway remodeling, including goblet cell hyperplasia, subepithelial fibrosis and myofibroblast hypertrophy, were also increased in OVA/OVA female mice. Moreover, serum total and OVA-specific IgE were significantly elevated in OVA/OVA female mice.
Conclusions: These results indicate that female mice are dominant in terms of forming airway remodeling as compared with male mice. The involvement of sex difference for sensitization and growth factor release in lung tissue based on inflammatory cell infiltration is indicated for the mechanism of sex difference of airway remodeling.
