Background The hygiene hypothesis has been proposed to explain the pathogenesis of asthma.Allergen exposure was shown to inhibit asthma in an animal model.But the optimal timing of allergen exposure remains unclear.Th...Background The hygiene hypothesis has been proposed to explain the pathogenesis of asthma.Allergen exposure was shown to inhibit asthma in an animal model.But the optimal timing of allergen exposure remains unclear.This study aims to explore the time effcct of allergen exposure and the possible mechanisms.Methods Neonate Wistar rats were randomly divided into asthma group,control group and day 1,day 3,day 7,and day 14 groups.The day 1,day 3,day 7 and day 14 groups were injected with ovalbumin （OVA） subcutaneously on days 1,3,7 and 14 after birth,respectively.Six weeks later,all groups,except the control group,were sensitized and stimulated with OVA to make the asthma model.We observed the pulmonary pathologic changes,detected the regulatory T cells,and CD28 expression level in thymus and spleen by flow cytometry.Results The asthmatic inflammation in the day 1,day 3 and day 7 groups,but not the day 14 group,was alleviated.The asthma group and day 14 group had lower proportions of regulatory T cells in the thymus compared with the control group,day 1,day 3,and day 7 groups.There was no significant difference in the CD28 expression levels on the regulatory and conventional T cells among groups.But the control group and the day 1,day 3,and day 7 groups had relatively higher proportions of CD28 positive regulatory T cells in the thymus than the day 14 group and the asthma group.Conclusions There is a “time-window” for early allergen exposure.The impairment of regulatory T cells may promote the development of asthma.Allergen exposure in the “time-window” can make the thymus produce normal quantity of regulatory cells.The CD28 signal on regulatory T cells may participate in the production of regulatory T cells.展开更多
Background Asthma is a complex disease involving genetic and environment interactions. Atopy is a strong risk factor for asthma. The airway epithelium not only forms a physical barrier but also provides immune defense...Background Asthma is a complex disease involving genetic and environment interactions. Atopy is a strong risk factor for asthma. The airway epithelium not only forms a physical barrier but also provides immune defense against harmful materials. To explore the effects of airway epithelium on asthma, we hypothesized that environmental injuries could act on bronchial epithelial cells and damage the physical barrier, which might facilitate allergens to stimulate immunoreactions and play an important role in the pathogenesis of asthma. Methods Thirty eight-week-old male Wistar rats were randomly divided into five groups with six rats in each group： control group, asthma group, ovalbumin （OVA）＋OVA group, lipopolysaccharide （LPS） group and LPS＋OVA group. In the control group, 0.9% saline was injected intraperitoneally on day 1. Fourteen days later, the rats were exposed to aerosolized 0.9% saline. In the asthma group, the rats were sensitized with an injection of 10 mg of OVA, followed by an aerosolized 2% OVA challenge14 days later. The OVA＋OVA group was sensitized by an inhalation 2% OVA, 20 minutes a day, from day 1 to day 7, and then OVA challenged in the same way as the asthma group. In the LPS group, LPS （200 μl, μg/μl） was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with saline as in the control group. While in the LPS＋OVA group, LPS （200 μl, 1 μg/μl） was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with OVA as in the asthma group. The expression of interleukin （IL）-4, interferon-gamma （IFN-γ） and thymic stromal lymphopoietin （TSLP） in the lungs was detected by reverse transcription polymerase chain reaction （RT-PCR） and the pulmonary pathological changes were also observed. The level of IL-4, IFN-γ and IgE in plasma was detected by enzyme-linked immunosorbent assay （ELISA）. Bronchoalveolar lavage fluid （BALF） was collected to conduct differential cell counts. Flow cytometry analysis was also used to count Thl and Th2 cells. Results The pathological changes in the LPS＋OVA group were similar to the asthma group, while in other groups, the pathological changes were not obvious. The ratio of lymphocytes in BALF, IL-4/IFN-γ in plasma and the expression of the TSLP and IL-4 in the asthma and LPS＋OVA groups were higher than in the control group and the OVA＋OVA group （P 〈0.05）. The level of IgE was higher in the asthma, LPS and LPS＋OVA groups than in the control group and the OVA＋OVA group （P 〈0.05）. By flow cytometry analysis, the Thl/Th2 ratio was lower in the LPS＋OVA and asthma groups than in other groups （P 〈0.05）. Conclusions The experiment results show that the injury to the bronchial epithelial layer may be the initial event of allergic responses. This finding implies that a rational approach to therapeutics would be to increase the resistance of the airways to environmental injuries rather than concentrating on suppressing inflammation.展开更多
文摘Background The hygiene hypothesis has been proposed to explain the pathogenesis of asthma.Allergen exposure was shown to inhibit asthma in an animal model.But the optimal timing of allergen exposure remains unclear.This study aims to explore the time effcct of allergen exposure and the possible mechanisms.Methods Neonate Wistar rats were randomly divided into asthma group,control group and day 1,day 3,day 7,and day 14 groups.The day 1,day 3,day 7 and day 14 groups were injected with ovalbumin （OVA） subcutaneously on days 1,3,7 and 14 after birth,respectively.Six weeks later,all groups,except the control group,were sensitized and stimulated with OVA to make the asthma model.We observed the pulmonary pathologic changes,detected the regulatory T cells,and CD28 expression level in thymus and spleen by flow cytometry.Results The asthmatic inflammation in the day 1,day 3 and day 7 groups,but not the day 14 group,was alleviated.The asthma group and day 14 group had lower proportions of regulatory T cells in the thymus compared with the control group,day 1,day 3,and day 7 groups.There was no significant difference in the CD28 expression levels on the regulatory and conventional T cells among groups.But the control group and the day 1,day 3,and day 7 groups had relatively higher proportions of CD28 positive regulatory T cells in the thymus than the day 14 group and the asthma group.Conclusions There is a “time-window” for early allergen exposure.The impairment of regulatory T cells may promote the development of asthma.Allergen exposure in the “time-window” can make the thymus produce normal quantity of regulatory cells.The CD28 signal on regulatory T cells may participate in the production of regulatory T cells.
文摘Background Asthma is a complex disease involving genetic and environment interactions. Atopy is a strong risk factor for asthma. The airway epithelium not only forms a physical barrier but also provides immune defense against harmful materials. To explore the effects of airway epithelium on asthma, we hypothesized that environmental injuries could act on bronchial epithelial cells and damage the physical barrier, which might facilitate allergens to stimulate immunoreactions and play an important role in the pathogenesis of asthma. Methods Thirty eight-week-old male Wistar rats were randomly divided into five groups with six rats in each group： control group, asthma group, ovalbumin （OVA）＋OVA group, lipopolysaccharide （LPS） group and LPS＋OVA group. In the control group, 0.9% saline was injected intraperitoneally on day 1. Fourteen days later, the rats were exposed to aerosolized 0.9% saline. In the asthma group, the rats were sensitized with an injection of 10 mg of OVA, followed by an aerosolized 2% OVA challenge14 days later. The OVA＋OVA group was sensitized by an inhalation 2% OVA, 20 minutes a day, from day 1 to day 7, and then OVA challenged in the same way as the asthma group. In the LPS group, LPS （200 μl, μg/μl） was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with saline as in the control group. While in the LPS＋OVA group, LPS （200 μl, 1 μg/μl） was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with OVA as in the asthma group. The expression of interleukin （IL）-4, interferon-gamma （IFN-γ） and thymic stromal lymphopoietin （TSLP） in the lungs was detected by reverse transcription polymerase chain reaction （RT-PCR） and the pulmonary pathological changes were also observed. The level of IL-4, IFN-γ and IgE in plasma was detected by enzyme-linked immunosorbent assay （ELISA）. Bronchoalveolar lavage fluid （BALF） was collected to conduct differential cell counts. Flow cytometry analysis was also used to count Thl and Th2 cells. Results The pathological changes in the LPS＋OVA group were similar to the asthma group, while in other groups, the pathological changes were not obvious. The ratio of lymphocytes in BALF, IL-4/IFN-γ in plasma and the expression of the TSLP and IL-4 in the asthma and LPS＋OVA groups were higher than in the control group and the OVA＋OVA group （P 〈0.05）. The level of IgE was higher in the asthma, LPS and LPS＋OVA groups than in the control group and the OVA＋OVA group （P 〈0.05）. By flow cytometry analysis, the Thl/Th2 ratio was lower in the LPS＋OVA and asthma groups than in other groups （P 〈0.05）. Conclusions The experiment results show that the injury to the bronchial epithelial layer may be the initial event of allergic responses. This finding implies that a rational approach to therapeutics would be to increase the resistance of the airways to environmental injuries rather than concentrating on suppressing inflammation.
