IL-13 and IL-4 cause eotaxin release in human airway smooth muscle cells: a role for ERK
IL-13 and IL-4 cause eotaxin release in human airway smooth muscle cells: a role for ERK
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DOI：
10.1152/ajplung.00245.2001
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发表时间：
2002-04-01
影响因子：
4.9
通讯作者：
Shore, SA
中科院分区：
文献类型：
--
作者：
Moore, PE;Church, TL;Shore, SA
人气道平滑肌(HASM)细胞表达白介素13(IL-13)和白介素4(IL-4)受体，并通过信号转导和转录激活因子-6以及细胞外信号调节激酶(ERK)的激活来反应这些细胞因子。本研究的目的是确定IL-13和/或IL-4是否影响HASM细胞中嗜酸粒细胞趋化因子的释放，以及ERK丝裂原活化蛋白(MAP)激酶通路是否参与了这些事件。用ELISA法检测HASM细胞培养上清液中嗜酸粒细胞趋化因子的释放，Northern印迹法检测嗜酸粒细胞趋化因子mRNA的表达。用IL-13或IL-4处理后，嗜酸性粒细胞趋化因子的释放呈浓度和时间依赖性，但IL-4更为有效。在用50 ng/mlIL-13或IL-4治疗后，嗜酸性粒细胞释放大约是基线的两倍(P<；0.001)。IL-13和IL-4与肿瘤坏死因子(TNF)-α有协同作用，可诱导嗜酸粒细胞趋化因子的释放：单独应用肿瘤坏死因子-α(10 ng/ml，作用24小时)可使嗜酸性粒细胞趋化因子的释放增加约4倍，而联合应用IL-13或IL-4则可使其增加10-20倍(P<；0.05)。嗜酸性粒细胞趋化蛋白mRNA的表达也得到了类似的结果。ERK上游的MAP/ERK激酶抑制剂U-0126(10um)或PD-98059(30um)可抑制IL-13或IL-4诱导的嗜酸性粒细胞趋化因子的释放(P<；0.05)。U-0126还抑制IL-13和肿瘤坏死因子-α诱导的mRNA表达。我们的结果表明，IL-13和IL-4通过部分涉及ERK激活的机制促使HASM细胞释放嗜酸性粒细胞趋化因子，提示平滑肌可能是导致哮喘嗜酸性粒细胞募集的重要趋化因子来源。
Human airway smooth muscle (HASM) cells express interleukin (IL)-13 and IL-4 receptors and respond to these cytokines with signal transducer and activator of transcription-6 and extracellular signal-regulated kinase (ERK) activation. The purpose of this study was to determine whether IL-13 and/or IL-4 influence eotaxin release in HASM cells and whether the ERK mitogen-activated protein (MAP) kinase pathway is involved in these events. Eotaxin release into HASM cell supernatants was assayed by ELISA, and eotaxin mRNA expression was determined by Northern blot analysis. Pretreatment with either IL-13 or IL-4 resulted in a concentration- and time-dependent release of eotaxin, although IL-4 was more effective. Eotaxin release was approximately twice baseline after treatment with 50 ng/ml IL-13 or IL-4 (P < 0.001). IL-13 and IL-4 also acted synergistically with tumor necrosis factor (TNF)-alpha to induce eotaxin release: TNF-alpha alone (10 ng/ml for 24 h) resulted in an approximately fourfold increase in eotaxin release, whereas TNF-alpha in combination with IL-13 or IL-4 resulted in 10- or 20-fold increases (P < 0.05). Similar results were obtained for eotaxin mRNA expression. Pretreatment with either U-0126 (10 muM) or PD-98059 (30 muM), both inhibitors of MAP/ERK kinase, the enzyme upstream of ERK, inhibited IL-13- or IL-4- induced eotaxin release (P < 0.05). U-0126 also inhibited IL-13, and TNF-alpha induced mRNA expression. Our results indicate that IL-13 and IL-4 cause eotaxin release in HASM cells through a mechanism that, in part, involves ERK activation and suggest that the smooth muscle may be an important source of chemokines leading to eosinophil recruitment in asthma.