Direct effects of interleukin-13 on signaling pathways for physiological responses in cultured human airway smooth muscle cells
Direct effects of interleukin-13 on signaling pathways for physiological responses in cultured human airway smooth muscle cells
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DOI：
10.1164/ajrccm.164.1.2008060
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发表时间：
2001-07-01
影响因子：
24.7
通讯作者：
Shore, SA
中科院分区：
文献类型：
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作者：
Laporte, JC;Moore, PE;Shore, SA
大量研究表明，Th 2细胞因子白细胞介素（IL）-13和IL-4在过敏性哮喘的发生发展中起重要作用。我们检验了IL-13和IL-4对培养的气道平滑肌细胞（HASM）有直接作用的假设。使用RT-PCR，我们发现HASM细胞表达IL-4 α、IL-13 R α I和IL-13 R α II的转录物，但不表达常见的IL-2 R γ链。然后，我们分析了这两种细胞因子激活HASM细胞中信号通路的能力。IL-13和IL-4均引起STAT-6磷酸化，但两种细胞因子之间的时间过程不同，在加入IL-4后15分钟和加入IL-13后1小时出现峰值效应。在低至0.3 ng/ml的细胞因子浓度下观察到对信号传导的影响。IL-4和IL-13也引起ERK MAP激酶的磷酸化。信号转导研究表明，两种细胞因子的生物学反应也不同。我们使用磁性扭转细胞术测量HASM细胞的细胞硬度，并测试IL-4和IL-13干扰由β-激动剂异丙肾上腺素（ISO）诱导的细胞硬度降低的能力。IL-13（50 ng/ml，24 h）而非IL-4显著降低HASM细胞的β-肾上腺素能反应性，并且MEK抑制剂U 0126显著降低IL-13对ISO诱导的细胞硬度变化的影响。我们认为IL-13对HASM细胞的这些直接作用可能至少部分导致哮喘患者中观察到的气道狭窄。
Numerous studies have suggested an important role for the Th2 cytokines interleukin (IL)-13 and IL-4 in the development of allergic asthma. We tested the hypothesis that IL-13 and IL-4 have direct effects on cultured airway smooth muscle cells (HASM). Using RT-PCR, we showed that HASM cells express transcripts for IL-4 alpha, IL-13R alphaI, and IL-13R alpha II, but not for the common IL-2R gamma chain. We then analyzed the capacity of the two cytokines to activate signaling pathways in HASM cells. Both IL-13 and IL-4 caused STAT-6 phosphorylation, but the time course was different between the two cytokines, with peak effects occurring 15 min after addition of IL-4 and 1 h after addition of IL-13. Effects on signaling were observed at cytokine concentrations as low as 0.3 ng/ml. IL-4 and IL-13 also caused phosphorylation of ERK MAP kinase. As suggested by the signaling studies, the biological responses of the two cytokines were also different. We used magnetic twisting cytometry to measure cell stiffness of HASM cells and tested the capacity of IL-4 and IL-13 to interfere with the reductions in cell stiffness induced by the beta -agonist isoproterenol (ISO). IL-13 (50 ng/ml for 24 h), but not IL-4, significantly reduced beta -adrenergic responsiveness of HASM cells, and the MEK inhibitor U0126 significantly reduced the effects of IL-13 on ISO-induced changes in cell stiffness. We propose that these direct effect of IL-13 on HASM cells may contribute at least in part to the airway narrowing observed in patients with asthma.