Essential role of GATA transcriptional factors in the activation of mast cells
Essential role of GATA transcriptional factors in the activation of mast cells
复制标题
DOI：
10.4049/jimmunol.178.1.360
复制
发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Matsuguchi, Tetsuya
中科院分区：
文献类型：
--
作者：
Masuda, Akio;Hashimoto, Katsunori;Matsuguchi, Tetsuya
肥大细胞是IgE介导的过敏反应中的关键效应细胞。加塔转录因子如GATA-1和加塔-2在肥大细胞中表达，最近的研究表明加塔-1和加塔-2都是肥大细胞发育所必需的。然而，加塔转录因子在分化的肥大细胞中的作用仍然是未知的。在本研究中，我们通过三种不同的方法（诱导性过表达显性阴性形式的加塔、药物失活或小干扰RNA技术）抑制加塔-1和加塔-2的活性，并分析加塔转录因子在肥大细胞活化中的分子机制。令人惊讶的是，分化的肥大细胞中加塔活性的抑制导致细胞存活、IgE诱导的脱粒和细胞因子产生的损害。在这些细胞中，与蛋白激酶C β相关的染色质中的信号转导和组蛋白修饰是缺陷的。这些结果表明，加塔在肥大细胞的活化中具有关键作用。
Mast cells are pivotal effector cells in IgE-mediated allergic reactions. GATA transcriptional factors such as GATA-I and GATA-2 are expressed in mast cells, and recent studies have revealed that both GATA-1 and GATA-2 are required for mast cell development. However, the role of GATA transcriptional factors in differentiated mast cells has remained largely unknown. In this study, we repressed the activity of GATA-1 and GATA-2 by using three different approaches (inducible overexpression of a dominant-negative form of GATA, pharmacological inactivation, or small interfering RNA technology), and analyzed the molecular mechanisms of GATA transcriptional factors in the activation of mast cells. Surprisingly, the repression of GATA activity in differentiated mast cells led to the impairment of cell survival, IgE-induced degranulation, and cytokine production. Signal transduction and histone modification in the chromatin related to protein kinase C beta were defective in these cells. These results identify that GATA has a critical role in the activation of mast cell.