Interleukin-1 alpha (IL-1 alpha) induces cell motility in a variety of benign cell types and in some but not all malignant cell lines in vitro. This study characterizes the IL-1 alpha-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell motility. IL-1 alpha significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1 alpha. Function-blocking monoclonal antibodies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration. When both the anti-IL-1 receptor antibodies are added together, the motility-response is completely blocked to control levels. Taken together the data indicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant inhibition of motility by neutralizing IL-1 alpha or blocking either one or both of the IL-1 receptors indicates an integration of IL-1-induced signals in the induction of melanoma cell migration.

译文

白细胞介素-1(IL-1 alpha)在多种良性细胞类型中以及某些但不是全部恶性细胞系中诱导细胞运动。这项研究的特点是表达I型和II型IL-1受体的侵略性人黑素瘤细胞系的IL-1α诱导的运动。我们测试了包括针对I型和II型IL-1受体的功能阻断性单抗的单克隆抗体对黑素瘤细胞运动性的影响,以确定哪个受体参与了IL-1α诱导的黑素瘤细胞运动性的信号转导。 IL-1α使用改良的Boyden室测定法以剂量依赖性方式显着增加MM-RU黑色素瘤细胞迁移,其浓度比明显抑制细胞生长的浓度低10至100倍。计算机辅助的延时图像分析表明,通过中和针对IL-1α的抗体,可以以剂量依赖性的方式抑制运动性。针对I型或II型IL-1受体的功能阻断性单克隆抗体显示出对细胞因子诱导的细胞迁移增强的显着抑制作用。当两种抗IL-1受体抗体一起添加时,运动反应完全被阻断至对照水平。数据合计表明,IL-1α诱导的MM-RU黑色素瘤细胞的运动是通过I型和II型IL-1受体介导的。通过中和IL-1α或阻断任何一个IL-1受体或两个IL-1受体来显着抑制运动性,这表明在黑素瘤细胞迁移的诱导中整合了IL-1诱导的信号。

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