Cross-linking of intercellular adhesion molecule 1 (CD54) induces AP-1 activation and IL-1beta transcription.
Cross-linking of intercellular adhesion molecule 1 (CD54) induces AP-1 activation and IL-1beta transcription.
复制标题
细胞间粘附分子 1 (CD54) 的交联诱导 AP-1 激活和 IL-1beta 转录。
作者：
Y. Koyama;Y. Tanaka;K. Saito;M. Abe;K. Nakatsuka;I. Morimoto;P. Auron;S. Eto
白细胞通过其整合素粘附于靶细胞，并在自我防御、炎症和分化中发挥关键作用。细胞间粘附分子-1（ICAM-1; CD 54）是整合素的代表性配体，并在许多细胞类型上表达，其中一些是白细胞粘附的靶点。最近的研究表明，粘附分子不仅作为细胞的胶水，而且作为一个信号转导。然而，ICAM-1的参与是否能够在靶细胞中诱导激活信号仍有待明确。在类风湿滑膜中，滑膜细胞表达大量ICAM-1，并产生多种炎性细胞因子，如IL-1 β。在这项研究中，我们提供了第一个证据表明，ICAM-1的参与诱导激活的转录因子AP-1和IL-1 β基因的转录使用一种特定的抗体交联ICAM-1类风湿性滑膜细胞系（E11细胞）。这些证据包括ICAM-1交联依赖性诱导1）原位IL-1 β转录和蛋白质合成，2）瞬时转染的氯霉素乙酰转移酶（CAT）报告质粒，其含有IL-1 β LPS应答增强子（在-3134和-2729之间）以及来自该增强子的AP-1位点的多个拷贝（在-3117和-3111之间），和3）Jun/Fos家族复合物与该AP-1位点的结合。因此，ICAM-1不仅作为整合素结合的粘合剂，而且作为对IL-1 β基因转录重要的AP-1激活信号的转换器。
Leukocytes adhere to target cells through their integrins and play a crucial role in self-defense, inflammation, and differentiation. Intercellular adhesion molecule-1 (ICAM-1; CD54) is a representative ligand for integrins and is expressed on many cell types, some of which are targets for leukocyte adhesion. Recent studies suggest that adhesion molecules function not only as a cellular glue, but also as a signal transducer. However, it remains to be clearly defined whether engagement of ICAM-1 is able to induce activation signals in target cells. In rheumatoid synovium, synovial cells are known to express abundant ICAM-1 and produce multiple inflammatory cytokines, such as IL-1beta. In this study, we provide the first evidence that ICAM-1 engagement induces activation of the transcription factor AP-1 and transcription of the IL-1beta gene using a specific Ab to cross-link ICAM-1 on a rheumatoid synovial cell line (E11 cells). This evidence includes ICAM-1 cross-linking-dependent induction of 1) in situ IL-1beta transcription and protein synthesis, 2) transiently transfected chloramphenicol acetyltransferase (CAT) reporter plasmids containing both the IL-1beta LPS-responsive enhancer (between -3134 and -2729) as well as multiple copies of an AP-1 site from this enhancer (between -3117 and -3111), and 3) the binding of a Jun/Fos family complex to this AP-1 site. Thus, ICAM-1 not only functions as a glue for integrin binding, but also as a transducer for AP-1 activation signals important for IL-1beta gene transcription.