Thymic stromal lymphopoietin-induced human asthmatic airway epithelial cell proliferation through an IL-13-dependent pathway

Thymic stromal lymphopoietin-induced human asthmatic airway epithelial cell proliferation through an IL-13-dependent pathway
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DOI:
10.1016/j.jaci.2010.01.044
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发表时间:
2010-04-01
影响因子:
14.2
通讯作者:
Chakir, Jamila
Chakir, Jamila
中科院分区:
医学1区
文献类型:
--
作者:
Semlali, Abdelhabib;Jacques, Eric;Chakir, Jamila

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背景:胸腺基质淋巴细胞生成素(TSLP)在过敏性气道炎症的发生中起关键作用。这种细胞因子是由几种类型的细胞,包括人类上皮cells.Objective:我们试图确定TSLP对增殖和修复的上皮细胞分离哮喘患者和健康subjects.Methods:表达TSLP受体(TSLPR)和其响应吸入皮质类固醇的健康对照组和哮喘患者的支气管活检标本通过免疫组化方法进行了评价。TSLPR,TSLP和IL-13的mRNA表达通过定量PCR测定,蛋白质表达通过ELISA和Western blotting测定从哮喘受试者中分离的上皮细胞与从健康对照受试者中分离的上皮细胞进行比较。结果:哮喘患者支气管活检标本及培养细胞中均有TSLPR表达,与正常对照组相比无显著性差异。吸入性皮质类固醇不影响这种表达。哮喘患者肺上皮细胞TSLP mRNA和蛋白水平显著高于健康对照组。TSLP刺激支气管上皮细胞产生IL-13。TSLP诱导气道上皮细胞增殖,促进上皮损伤修复。这种效果被废除与IL-13 neutralization.Conclusions:我们的数据表明,上皮细胞表达TSLPR和TSLP诱导支气管上皮细胞增殖,并通过IL-13的生产增加损伤修复。这表明TSLP和IL-13环在上皮细胞增殖和修复中起稳态作用。(J Allergy Clin Immunol 2010;125:844-50.)
Background: Thymic stromal lymphopoietin (TSLP) plays a pivotal role in the initiation of allergic airway inflammation. This cytokine is produced by several cell types, including human epithelial cells.Objective: We sought to determine the effect of TSLP on proliferation and repair of epithelial cells isolated from asthmatic patients and healthy subjects.Methods: Expression of TSLP receptor (TSLPR) and its response to inhaled corticosteroids was evaluated on bronchial biopsy specimens of healthy control subjects and asthmatic patients by means of immunohistochemistry. TSLPR, TSLP, and IL-13 mRNA expression was determined by means of quantitative PCR, and protein expression was measured by means of ELISA and Western blotting in epithelial cells isolated from asthmatic subjects compared with those isolated from healthy control subjects. The effect of TSLP on cell proliferation and wound healing was performed.Results: TSLPR is expressed by bronchial epithelial cells in bronchial biopsy specimens and in cultured cells, with no difference between asthmatic patients and healthy control subjects. Inhaled corticosteroids did not affect this expression. TSLP mRNA and protein levels were significantly higher in epithelial cells isolated from asthmatic patients compared with those from healthy control subjects. TSLP stimulated IL-13 production by bronchial epithelial cells. TSLP induced airway epithelial cell proliferation and enhanced epithelial injury repair. This effect was abrogated with IL-13 neutralization.Conclusions: Our data indicate that epithelial cells express TSLPR and that TSLP induces bronchial epithelial cell proliferation and increases injury repair through IL-13 production. This suggests that TSLP and IL-13 loops play a homeostatic role on epithelial cell proliferation and repair. (J Allergy Clin Immunol 2010;125:844-50.)