T cell-specific negative regulation of transcription of the human cytokine IL-4.
T cell-specific negative regulation of transcription of the human cytokine IL-4.
复制标题
T 细胞特异性负调节人类细胞因子 IL-4 的转录。
DOI：
10.4049/jimmunol.148.6.1913
复制
发表时间：
1992
影响因子：
4.4
通讯作者：
Peter H. Krammer
中科院分区：
文献类型：
--
作者：
M. Li‐Weber;Astrid Eder;H. Krafft;Peter H. Krammer
由活化的T细胞分泌的IL-4是一种多效性细胞因子，影响不同细胞类型如T细胞、B细胞和肥大细胞的生长和分化。我们研究了人IL-4启动子的上游调控元件。在IL-4基因5'端侧翼区发现一个新的T细胞特异性负调控元件（NRE）：-311CTCCCTTCT-303（NRE-Ⅰ）和-288 CTTTTTGCTT-TGC-300（NRE-Ⅱ）。鉴定了分别与NRE-I和NRE-II结合的T细胞特异性蛋白Neg-1和普遍存在的蛋白Neg-2。此外，在NRE下游45 bp处发现了一个正调控元件。当NRE存在时，PRE的增强子活性被完全抑制。这些数据表明，IL-4启动子活性通常通过抑制增强子正调控元件被NRE下调。这些数据可能对T细胞中IL-4表达的严格控制有影响。
IL-4 secreted by activated T cells is a pleiotropic cytokine affecting growth and differentiation of diverse cell types such as T cells, B cells, and mast cells. We investigated the upstream regulatory elements of the human IL-4 promoter. A novel T cell-specific negative regulatory element (NRE) composed of two protein-binding sites were mapped in the 5' flanking region of the IL-4 gene: -311CTCCCTTCT-303 (NRE-I) and -288CTTTTTGCTT-TGC-300 (NRE-II). A T cell-specific protein Neg-1 and a ubiquitous protein Neg-2 binding to NRE-I and NRE-II, respectively, were identified. Furthermore, a positive regulatory element was found 45 bp downstream of the NRE. The enhancer activity of the PRE was completely suppressed when the NRE was present. These data suggest that IL-4 promoter activity is normally down-regulated by an NRE via repression of the enhancer positive regulatory element. These data may have implications for the stringent control of IL-4 expression in T cells.