呼吸道合胞病毒感染促进胸腺基质淋巴细胞生成素的产生并加速小鼠气道中的Th2炎症
[Respiratory syncytial virus infection promotes the production of thymic stromal lymphopoietin and accelerates Th2 inflammation in mouse airway].
作者信息
Xia Hu, Cai Shao-xi, Tong Wan-cheng, Luo Li-min, Yu Hua-peng
机构信息
Department of Respiratory Disease, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2009 Apr;29(4):724-8.
OBJECTIVE
To investigate the effect of respiratory syncytial virus (RSV) infection on the production of thymic stromal lymphopoietin (TSLP) and Th1/Th2 balance in asthmatic mice.
METHODS
Thirty-two female BALB/c mice were randomly divided into 4 groups, namely the PBS group, ovalbumin (OVA) group, RSV group and OVA/RSV group. The mice were sensitized by OVA and then stimulated with nebulized OVA, and RSV was inoculated into the nasal cavity of the mice. BUXCO noninvasive lung function detection was performed to examine the airway response to metacholine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of IL-4, IL-5, IL-13, and IFN-gamma in the mice. The cells in the bronchoalveolar lavage fluid (BALF) were counted and classified, and the supernatants of the BALF were used for the detection of TSLP. Histopathological changes in the lung tissues of the mice were examined using HE staining, and immunohistochemistry using anti-mouse TSLP antibody was performed to examine TSLP expressions in the airway epithelial cells.
RESULTS
RSV infection promoted the production of TSLP in the asthmatic mice, and the concentration of TSLP in OVA/RSV group (2.13-/+0.05 ng/ml) was significantly higher than that in the other groups (P<0.01). RSV infection increased the serum levels of IL-4, IL-5, IL-13, and IFN-gamma in the mice. The total BALF cells, eosinophils, lymphocytes and neutrophils in OVA/RSV group were significantly higher than those in the other groups; noninvasive lung function examination showed higher Penh value in OVA/RSV group (318.66-/+50.87) than in the other groups when the inhaled metacholine increased to 6.25 mg/ml (P<0.01). More obvious and extensive airway inflammatory cell infiltration in OVA/RSV group were observed, and immunohistochemical staining also showed higher expression of TSLP in the airway epithelial cells of OVA/RSV group.
CONCLUSIONS
RSV infection promotes the production of TSLP in the airway epithelial cells and increases the level of Th2 cytokines in asthmatic mice. Concurrent RSV infection can exacerbate Th2 inflammatory reaction in asthmatic mice.
目的
探讨呼吸道合胞病毒(RSV)感染对哮喘小鼠胸腺基质淋巴细胞生成素(TSLP)产生及Th1/Th2平衡的影响。
方法
将32只雌性BALB/c小鼠随机分为4组,即PBS组、卵清蛋白(OVA)组、RSV组和OVA/RSV组。小鼠用OVA致敏,然后用雾化OVA刺激,RSV接种于小鼠鼻腔。采用BUXCO无创肺功能检测法检测小鼠对乙酰甲胆碱的气道反应,并用酶联免疫吸附测定(ELISA)法检测小鼠血清中IL-4、IL-5、IL-13和IFN-γ水平。对支气管肺泡灌洗液(BALF)中的细胞进行计数和分类,BALF上清液用于检测TSLP。用HE染色检查小鼠肺组织的组织病理学变化,并用抗小鼠TSLP抗体进行免疫组织化学检测气道上皮细胞中TSLP的表达。
结果
RSV感染促进哮喘小鼠TSLP的产生,OVA/RSV组TSLP浓度(2.13±0.05 ng/ml)显著高于其他组(P<0.01)。RSV感染增加了小鼠血清中IL-4、IL-5、IL-13和IFN-γ水平。OVA/RSV组BALF细胞总数、嗜酸性粒细胞、淋巴细胞和中性粒细胞显著高于其他组;无创肺功能检查显示,当吸入乙酰甲胆碱增加到6.25 mg/ml时,OVA/RSV组的Penh值(318.66±50.87)高于其他组(P<0.01)。观察到OVA/RSV组气道炎症细胞浸润更明显、更广泛,免疫组织化学染色也显示OVA/RSV组气道上皮细胞中TSLP表达更高。
结论
RSV感染促进哮喘小鼠气道上皮细胞中TSLP的产生,增加Th2细胞因子水平。RSV合并感染可加重哮喘小鼠的Th2炎症反应。