健康研究
健康研究
건강연구
HEALTH RESEARCH
2009年
1期
7-13,封2
,共8页
史丽云%周卸来%尹红萍%蔡玲斐%GARG Hari G%严杰
史麗雲%週卸來%尹紅萍%蔡玲斐%GARG Hari G%嚴傑
사려운%주사래%윤홍평%채령비%GARG Hari G%엄걸
胸腺基质淋巴生成素受体%哮喘
胸腺基質淋巴生成素受體%哮喘
흉선기질림파생성소수체%효천
thymic stromal lymphopoietin receptor%asthma
目的 为阐明胸腺基质淋巴生成素受体(Thymic stromal lymphopoietin receptor,TSLPR)在超敏原引起的气道炎症应答中的作用,并在小鼠模型中探讨局部封闭TSLPR用以缓解哮喘的可能性.方法 对TSLPR抗体或同型抗体预处理,且以鸡卵白蛋白(OVA)诱导的各组小鼠,分别行气道浸润细胞的分类和记数、H＆E和PAS的肺组织染色分析;并以酶联免疫吸附测定法(ELISA)检测支气管肺泡灌洗液中炎性细胞因子;进一步分析OVA激发的小鼠树突状细胞(DCs)的迁移能力和成熟状态.结果 在小鼠OVA致敏前施以抗TSLPR抗体可显著减少气道粘液的分泌、嗜酸性粒细胞和淋巴细胞浸润;同时引发IL-4、IL-5水平的明显下降.而作为其机制之一,TSLPR的中和作用可阻止超敏原诱导的DCs的成熟和迁移.结论 封闭TSLPR介导的信号通路可缓解哮喘小鼠的气道炎症反应,有望成为一项新的防治气道变应性疾病策略.
目的 為闡明胸腺基質淋巴生成素受體(Thymic stromal lymphopoietin receptor,TSLPR)在超敏原引起的氣道炎癥應答中的作用,併在小鼠模型中探討跼部封閉TSLPR用以緩解哮喘的可能性.方法 對TSLPR抗體或同型抗體預處理,且以鷄卵白蛋白(OVA)誘導的各組小鼠,分彆行氣道浸潤細胞的分類和記數、H＆E和PAS的肺組織染色分析;併以酶聯免疫吸附測定法(ELISA)檢測支氣管肺泡灌洗液中炎性細胞因子;進一步分析OVA激髮的小鼠樹突狀細胞(DCs)的遷移能力和成熟狀態.結果 在小鼠OVA緻敏前施以抗TSLPR抗體可顯著減少氣道粘液的分泌、嗜痠性粒細胞和淋巴細胞浸潤;同時引髮IL-4、IL-5水平的明顯下降.而作為其機製之一,TSLPR的中和作用可阻止超敏原誘導的DCs的成熟和遷移.結論 封閉TSLPR介導的信號通路可緩解哮喘小鼠的氣道炎癥反應,有望成為一項新的防治氣道變應性疾病策略.
목적 위천명흉선기질림파생성소수체(Thymic stromal lymphopoietin receptor,TSLPR)재초민원인기적기도염증응답중적작용,병재소서모형중탐토국부봉폐TSLPR용이완해효천적가능성.방법 대TSLPR항체혹동형항체예처리,차이계란백단백(OVA)유도적각조소서,분별행기도침윤세포적분류화기수、H＆E화PAS적폐조직염색분석;병이매련면역흡부측정법(ELISA)검측지기관폐포관세액중염성세포인자;진일보분석OVA격발적소서수돌상세포(DCs)적천이능력화성숙상태.결과 재소서OVA치민전시이항TSLPR항체가현저감소기도점액적분비、기산성립세포화림파세포침윤;동시인발IL-4、IL-5수평적명현하강.이작위기궤제지일,TSLPR적중화작용가조지초민원유도적DCs적성숙화천이.결론 봉폐TSLPR개도적신호통로가완해효천소서적기도염증반응,유망성위일항신적방치기도변응성질병책략.
Objective To define the role of Thymic stromal lymphopoietin receptor (TSLPR) in allergen-primed airway inflammatory responses, and to investigate the possibility of alleviating allergic disorders by locally inhibiting TSLPR in an asthmatic mice model. Methods In the anti-TSLPR antibody or isotype-imraunoglobulin pretreated, ovalbumin ( OVA )-primed mice, the airway infiltrated cells were fractioned and counted, and histologic analysis of lung tissues was conducted by staining with hematoxylin and eosin ( H&E) and periodic acid schiff ( PAS) respectively. Also the levels of proinflammatory cytokines in bronchoalveolar lavage (BAL) were analyzed by ELISA. The effects of TSLPR inhibition on allergen-initiated responses were further evaluated by assessing the migratory ability and the maturation of OVA-induced dendritic cell ( DC). Results Application of Anti-TSLPR antibody before OVA sensitization significantly decreased mucus production and infiltrated eosinophils and lymphocytes in asthmatic mice, together with a remarkable reduction of 1L-4, IL-5 levels in BAL. As a mechanism of this effect, neutralization of TSLPR inhibited the maturation and migration of DCs in response to allergen stimulation. Conclusion Blockade of TSLPR-mediated signaling alleviated the allergic airway inflammation, representing a novel strategy in treating airway atopic disorders.
