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Activation of protease-activated receptor-2 reduces airways inflammation in experimental allergic asthma.

机译:蛋白酶激活受体2的激活减少了实验性过敏性哮喘中的气道炎症。

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BACKGROUND: Proteinase-activated receptors (PAR)-2 are members of the family of G-protein-coupled receptors activated by proteases. These receptors are widely expressed in several tissues and in virtually all cells involved in rhinitis and asthma. In particular, proteinases activating PAR-2 may affect airway functions and play a role in human diseases. OBJECTIVE: Assessment of the role of PAR-2 in bronchoconstriction, airway responsiveness and immune response after allergic challenge, in rabbits sensitized to Par j 1, the major allergen of Parietaria judaica pollen. METHODS: Evaluation of antigen challenge in rabbits treated with PAR-2-activating peptide (PAR-2AP) (SLIGRL) or the scrambled peptide LSIGRL or vehicle immediately before allergen exposure measuring airway responsiveness. Characterization of bronchoalveolar lavage (BAL) following histamine challenge and phenotype analysis of cells by flow cytometry and analysis of cytokine production by quantitative PCR. RESULTS: PAR-2AP pre-treatment, but not the scrambled peptide, was able to significantly inhibit bronchoconstriction, airway hyper-responsiveness and to modulate the immune response induced by allergic challenge in sensitized rabbits. The phenotype analysis of the cells recovered from BAL showed an increase in RLA-DR-positive cells while RTLA-positive cells were unchanged. IFN-gamma and IL-2 production were inhibited, with a concomitant increase in IL-10 of about 10-fold over the control values. CONCLUSIONS: In this experimental model, PAR-2 modulates bronchoconstriction interfering with antigen challenge-induced immune response in rabbits sensitized and challenged to Par j 1.
机译:背景:蛋白酶激活受体(PAR)-2是被蛋白酶激活的G蛋白偶联受体家族的成员。这些受体在鼻炎和哮喘涉及的几个组织和几乎所有细胞中广泛表达。尤其是,激活PAR-2的蛋白酶可能会影响气道功能并在人类疾病中发挥作用。目的:评估对Parietaria judaica花粉的主要过敏原Par j 1致敏的兔子中,PAR-2在过敏性攻击后支气管收缩,气道反应性和免疫反应中的作用。方法:在过敏原暴露前立即评估用PAR-2-活化肽(PAR-2AP)(SLIGRL)或加扰肽LSIGRL或运载体处理的兔的抗原攻击,以测量气道反应性。组胺攻击和通过流式细胞仪对细胞的表型分析后的支气管肺泡灌洗(BAL)的表征,并通过定量PCR分析细胞因子的产生。结果:PAR-2AP预处理可显着抑制致敏兔子的支气管收缩,气道高反应性并调节由过敏性激发所诱导的免疫反应,但不能抑制混乱的肽。从BAL中回收的细胞的表型分析显示RLA-DR阳性细胞增加,而RTLA阳性细胞未改变。 IFN-γ和IL-2的产生被抑制,IL-10的增加比对照值高约10倍。结论:在这个实验模型中,PAR-2调节支气管收缩,干扰抗原挑战并激发对Par j 1的兔子的抗原挑战诱导的免疫反应。

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