Regulation of Epidermal Growth Factor Receptor Expression and Morphology of Lung Epithelial Cells by Interleukin-1β
Regulation of Epidermal Growth Factor Receptor Expression and Morphology of Lung Epithelial Cells by Interleukin-1β
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IL-1β对肺上皮细胞表皮生长因子受体表达和形态的调节
DOI：
10.1093/jb/mvaa015
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Yamamoto Hideyuki
中科院分区：
文献类型：
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作者：
Nakayama Izumi;Higa-Nakamine Sayomi;Uehara Ayako;Sugahara Kazuhiro;Kakinohana Manabu;Yamamoto Hideyuki
越来越多的证据表明，表皮生长因子受体（EGFR）的过度活化参与了成人呼吸窘迫综合征和肺纤维化的发生发展。阐明炎症性肺部疾病期间调节EGFR在质膜上驻留的机制对于确定潜在的治疗方法很重要。我们已经证明，鞭毛蛋白磷酸化EGFR的Ser 1047和诱导瞬时EGFR内化。本研究旨在探讨白细胞介素1 β（IL-1β）对肺泡上皮细胞EGFR表达的影响及其分子途径。用IL-1β处理A549细胞可诱导p38丝裂原活化蛋白激酶（MAP激酶）和MAP激酶活化蛋白激酶-2（MAPKAPK-2）活化，以及EGFR丝氨酸1047磷酸化。p38 MAP激酶抑制剂SB 203580可抑制MAPKAPK-2活化和EGFR磷酸化。此外，MK 2a抑制剂（MAPKAPK-2抑制剂）抑制EGFR磷酸化。对细胞表面蛋白的生物素化的评估表明IL-1β诱导EGFR内化。此外，用IL-1β长期处理A549细胞引起形态学变化和细胞-细胞接触的丧失。此外，IL-1β增强了转化生长因子β 1对上皮-间充质转化的作用。提示IL-1β可调节EGFR的功能，并引起肺泡上皮细胞形态学改变。
Accumulating evidences suggested that the overactivation of epidermal growth factor receptor (EGFR) was involved in the development of adult respiratory distress syndrome and pulmonary fibrosis. Elucidation of the mechanisms that regulate EGFR residence on the plasma membrane during inflammatory lung conditions is important for identifying potential therapies. We have demonstrated that flagellin phosphorylated EGFR at Ser1047 and induced transient EGFR internalization. In this study, we examined the molecular pathway and effect of interleukin 1 beta (IL-1β) on EGFR in alveolar epithelial cells. Treatment of A549 cells with IL-1β induced the activation of p38 mitogen-activated protein kinase (MAP kinase) and MAP kinase-activated protein kinase-2 (MAPKAPK-2), as well as EGFR phosphorylation at serine 1047. Both MAPKAPK-2 activation and EGFR phosphorylation were inhibited by SB203580, a p38 MAP kinase inhibitor. In addition, MK2a inhibitor (a MAPKAPK-2 inhibitor) suppressed EGFR phosphorylation. Assessment of the biotinylation of cell surface proteins indicated that IL-1β induced EGFR internalization. Furthermore, long-term treatment of A549 cells with IL-1β caused morphological changes and loss of cell–cell contact. Moreover, IL-1β augmented the effect of transforming growth factor beta 1 on the epithelial–mesenchymal transition. These results suggested that IL-1β regulates EGFR functions and induces morphological changes of alveolar epithelial cells.