Airway epithelial cells from asthmatic children differentially express proremodeling factors.
Airway epithelial cells from asthmatic children differentially express proremodeling factors.
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DOI：
10.1016/j.jaci.2011.11.035
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Debley JS
中科院分区：
文献类型：
--
作者：
Lopez-Guisa JM;Powers C;File D;Cochrane E;Jimenez N;Debley JS
气道上皮可以表达驱动上皮下气道重塑的因子。 TGF-β2、血管上皮生长因子 (VEGF)、解整合素和金属蛋白酶 33 (ADAM33) 和骨膜素被推测参与上皮下重塑，并在成人哮喘气道中过度表达。流行病学数据表明，哮喘患者的肺功能缺陷是在儿童时期获得的。我们试图确定与来自特应性非哮喘和健康儿童的细胞相比，来自哮喘儿童的气道上皮细胞 (AEC) 是否在本质上或对 IL-4/IL-13 刺激的反应中差异表达 TGF-β2、VEGF、ADAM33 或骨膜素。支气管和鼻上皮细胞是在选择性手术完成麻醉后，从特征明确的哮喘儿童 (n = 16)、特应性非哮喘儿童 (n = 9) 和健康儿童 (n = 15) 的刷牙中获得的。在气液界面 (ALI) 分化 3 周后，对条件培养基进行取样，并从未刺激和 IL-4/IL-13 刺激的培养物中提取 RNA。使用 ELISA 测量 TGF-β2 和 VEGF 水平。使用实时 PCR 评估 ADAM33 和骨膜蛋白表达。哮喘儿童的支气管和鼻 ALI 培养物中 TGF-β2 和 VEGF 的产生显着高于特应性非哮喘儿童和健康儿童的培养物。 IL-4/IL-13 刺激后，哮喘培养物中 TGF-β2 水平显着增加。鼻腔和支气管 ALI 产生的 TGF-β2 (r = 0.64，P = .001) 和 VEGF (r = 0.73，P < .001) 之间的受试者内相关性良好。与特应性非哮喘或健康儿童的细胞相比，哮喘儿童的支气管细胞中的骨膜素表达高出 3.7 倍 (P < .001)，鼻细胞中的骨膜素表达高出 3.9 倍 (P < .004)。与来自特应性非哮喘或健康儿童的细胞相比，哮喘患者的 AEC 中 ADAM33 的表达没有差异。与来自特应性非哮喘和健康儿童的细胞相比，来自哮喘儿童的 AEC 差异表达 TGF-β2、VEGF 和骨膜素。鼻上皮细胞可能是支气管细胞的合适替代物，可以促进未来纵向儿科研究中气道上皮的研究。
The airway epithelium can express factors that drive subepithelial airway remodeling. TGF-β2, vascular epithelial growth factor (VEGF), a disintegrin and metalloprotease 33 (ADAM33), and periostin are hypothesized to be involved in subepithelial remodeling and are overexpressed in adult asthmatic airways. Epidemiologic data suggest that lung function deficits in asthmatic patients are acquired in childhood. We sought to determine whether airway epithelial cells (AECs) from asthmatic children differentially express TGF-β2, VEGF, ADAM33, or periostin compared with cells from atopic nonasthmatic and healthy children intrinsically or in response to IL-4/IL-13 stimulation. Bronchial and nasal epithelial cells were obtained from brushings from well-characterized asthmatic (n = 16), atopic nonasthmatic (n = 9), and healthy (n = 15) children after achievement of anesthesia for elective procedures. After differentiation at an air-liquid interface (ALI) for 3 weeks, conditioned media were sampled and RNA was extracted from unstimulated and IL-4/IL-13–stimulated cultures. TGF-β2 and VEGF levels were measured with ELISA. ADAM33 and periostin expression was assessed by using real-time PCR. TGF-β2 and VEGF production was significantly greater in bronchial and nasal ALI cultures from asthmatic children than in cultures from atopic nonasthmatic and healthy children. TGF-β2 levels increased significantly in asthmatic cultures after IL-4/IL-13 stimulation. Within-subject correlation between nasal and bronchial ALI production of TGF-β2 (r = 0.64, P = .001) and VEGF (r = 0.73, P < .001) was good. Periostin expression was 3.7-fold higher in bronchial cells (P < .001) and 3.9-fold higher in nasal cells (P < .004) from asthmatic children than in cells from atopic nonasthmatic or healthy children. ADAM33 was not differentially expressed by AECs from asthmatic patients compared with that from cells from atopic nonasthmatic or healthy children. AECs from asthmatic children differentially express TGF-β2, VEGF, and periostin compared with cells from atopic nonasthmatic and healthy children. Nasal epithelial cells might be a suitable surrogate for bronchial cells that could facilitate investigation of the airway epithelium in future longitudinal pediatric studies.
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5.8
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