| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
[Background] Air pollution contributes to both exacerbation and development of bronchial asthma. We have reported that co-exposure to air pollution directly promotes sensitization to inhaled allergen in neonatal mice.
[Objective] We investigated whether prenatal exposure to air pollution could also increase susceptibility to development of asthma in early life.
[Method] Pregnant female BALB/c mice were exposed to aerosolised leachate of residual oil fly ash (ROFA, 50mg/ml, 30 min) at 5, 3 and 1 days before delivery. Offspring were treated once at 3-day of life with ovalbumin (OVA 5 ug) and alum (i.p.), an intentionally sub-optimal dose for sensitization, exposed to aerosolised OVA (1%, 10 min) at 12 - 14 days or 32 - 35 days of age, and evaluated two days after the final exposure.
[Result] The offspring of ROFA-exposed mothers (ROFA group ) revealed increasing airway hyperresponsiveness (higher Penh value to methacholine challenge) and had substantial numbers of eosinophils in the BALF (ROFA group vs. control : 0.66 +/- 0.17 vs. 0.06 +/- 0.02 (x 10^5/ml, mean +/- S.E., 2-week-old mice), p < 0.01). Histopathology revealed prominent inflammation in the lungs of ROFA group and they showed increased allergen-specific IgE and IgG1 levels. Their cultured splenocytes showed an increased IL-4/IFN-gamma cytokine, indicating Th2 skewed immunity.
[Conclusion] The data indicated that exposure of pregnant female mice to an air pollutant aerosol increased asthma susceptibility of their offspring.
[Further study] Clinical studies suggest a role for angiogenesis in the development and persistence of chronic asthma. We investigated a role of vascular endothelial growth factor (VEGF), a major angiogenic and proinflammatory mediator, in allergen-induced acute asthma and to determine whether endostatin/Fc, a potent anti-angiogenic factor can attenuate allergic airway responses.
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