Expression and function of the ST2 gene in a murine model of allergic airway inflammation
Expression and function of the ST2 gene in a murine model of allergic airway inflammation
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DOI：
10.1046/j.1365-2745.2002.01494.x
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发表时间：
2002-10-01
影响因子：
6.1
通讯作者：
Sugiyama, Y
中科院分区：
文献类型：
--
作者：
Oshikawa, K;Yanagisawa, K;Sugiyama, Y
背景我们最近报道了可溶性ST 2蛋白在哮喘患者血清中的水平升高，并且与哮喘急性发作的严重程度密切相关。目的探讨可溶性小鼠（m）ST 2在小鼠哮喘模型中的表达及其动力学特征。方法采用免疫组织化学方法检测小鼠哮喘模型血清和肺组织中可溶性ST 2基因和蛋白表达的动态变化，并与正常对照组比较。结果在哮喘模型中，m ST 2基因和蛋白表达均明显高于正常对照组，但在哮喘发病中的作用、功能和动力学机制尚不清楚。（卵清蛋白; OVA）攻击，mST 2蛋白对体外从致敏小鼠脾细胞产生的OVA诱导的Th 2细胞因子的影响，结果过敏原刺激后3 h血清mST 2蛋白水平达最高水平，而血清IL-5水平未达高峰。过敏原刺激诱导肺组织mST 2 mRNA表达，脾组织mST 2 mRNA表达进行组成型检测。此外，用mST 2蛋白预处理显著抑制体外OVA刺激的脾细胞产生IL-4和IL-5，但不抑制IFN-γ，并且静脉内mST 2基因转移导致支气管肺泡灌洗液中嗜酸性粒细胞数量和IL-4和IL-5水平的急剧减少，结论过敏原暴露后内源性mST 2蛋白表达增加可能调节Th 2介导的气道炎症，并且mST 2的体内基因转移可应用于变应性疾病的新型免疫疗法。
Background We have recently reported that soluble ST2 protein levels are elevated in the sera of patients with asthma, and correlate well with the severity of asthma exacerbation. However, the role, function, and kinetics of soluble ST2 expression in asthma remain unclear.Objective The objective of the present study was to clarify the function and kinetics of soluble murine (m) ST2 expression in a murine asthma model.Methods We analyzed the kinetics of gene and protein expression of mST2 in sera or lung tissue after allergen (ovalbumin; OVA) challenge in a murine model of allergic airway inflammation, the effects of mST2 protein on OVA-induced Th2 cytokine production in vitro from splenocytes of sensitized mice, and the effects of soluble mST2 on Th2-dependent allergic airway inflammation by in vivo gene transfer of mST2.Results Serum mST2 protein levels increased to the maximal level 3 h after the allergen challenge, before serum IL-5 levels peaked. The mRNA expression of mST2 in lung tissue was induced after the allergen challenge, while that in the spleen was constitutively detected. Furthermore, pre-treatment with mST2 protein significantly inhibited the production of IL-4 and IL-5, but not IFN-gamma, from OVA-stimulated splenocytes in vitro, and intravenous mST2 gene transfer resulted in a drastic reduction in the number of eosinophils and in the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid, compared with those in response to transfer of non-coding plasmid vector or of lipid alone.Conclusion These results suggest that increases in endogenous mST2 protein after allergen exposure may modulate Th2-mediated airway inflammation, and that in vivo gene transfer of mST2 can be applicable to use in a novel immunotherapy for allergic diseases.