IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells
IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells
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DOI：
10.1172/jci13557
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发表时间：
2001-12-01
影响因子：
15.9
通讯作者：
Tournier, F
中科院分区：
文献类型：
--
作者：
Laoukili, J;Perret, E;Tournier, F
在哮喘动物模型中，白介素13(IL-13)可诱导杯状细胞化生、嗜酸性粒细胞在支气管粘膜的浸润和高反应性，但其对呼吸道上皮细胞的作用机制尚不清楚。在哮喘和其他慢性肺部炎症性疾病中常见的上皮屏障损伤通过上皮细胞的增殖、迁移和分化来修复。因此，炎症过程可能会影响上皮细胞的再生。因此，我们研究了IL-13对原代培养的人鼻上皮细胞黏液纤毛分化的影响。我们发现IL-13改变纤毛细胞分化，增加分泌细胞的比例。IL-13下调肌动蛋白结合蛋白Ezrin和其他细胞骨架成分的表达。IL-13还损害侧向细胞接触，干扰Ezrin在分化的纤毛细胞中的顶端定位。此外，IL-4拮抗突变蛋白(Y124D)与IL-4受体cc亚单位(IL-4和IL-13受体的共同链)结合，抑制IL-13‘S效应。IL-13还以时间和剂量依赖的方式降低纤毛搏动频率。这些结果表明，在人类过敏性哮喘反应中，IL-13影响纤毛细胞和分泌细胞的分化，导致呼吸道损伤和阻塞。
In animal models of asthma, interleukin-13 (IL-13) induces goblet cell metaplasia, eosinophil infiltration of the bronchial mucosa, and bronchial hyperreactivity, but the basis of its effects on airway epithelia remain unknown. Lesions of the epithelial barrier, frequently observed in asthma and other chronic lung inflammatory diseases, are repaired through proliferation, migration, and differentiation of epithelial cells. An inflammatory process may then, therefore, influence epithelial regeneration. We have thus investigated the effect of IL-13 on mucociliary differentiation of human nasal epithelial cells in primary culture. We show that IL-13 alters ciliated cell differentiation and increases the proportion of secretory cells. IL-13 downregulates the actin-binding protein ezrin and other cytoskeletal components. IL-13 also impairs lateral cell contacts and interferes with the apical localization of ezrin seen in differentiated ciliated cells. In addition, an IL-4 antagonistic mutant protein (Y124D), which binds to the IL-4 receptor cc subunit, a common chain of IL-4 and IL-13 receptors, inhibits IL-13's effects. IL-13 also decreases ciliary beat frequency in a time- and dose-dependent manner. These results suggest that, in human allergic asthmatic responses, IL-13 affects both ciliated and secretory cell differentiation, leading to airway damage and obstruction.