PI3K Is a Linker Between L-selectin and PSGL-1 Signaling to IL-18 Transcriptional Activation at the Promoter Level.
PI3K Is a Linker Between L-selectin and PSGL-1 Signaling to IL-18 Transcriptional Activation at the Promoter Level.
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PI3K 是 L-选择素和 PSGL-1 之间的连接物，在启动子水平上向 IL-18 转录激活发出信号。
DOI：
10.1007/s10753-017-0711-5
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发表时间：
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期刊：
影响因子：
5.1
通讯作者：
Jixian Luo
中科院分区：
文献类型：
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作者：
Jixian Luo
L-选择素和P-选择素糖蛋白配体-1（PSGL-1）是两种具有相似生理功能的粘附分子。我们以前的论文表明，磷脂酰肌醇3-激酶（PI 3 K）在L-选择素和PSGL-1介导的F-肌动蛋白的重新分布和组装过程中起着至关重要的作用，中性粒细胞滚动E-选择素。然而，尚不清楚L-选择素和PSGL-1是否通过PI 3 K诱导其他类似的生理事件。在这里，我们研究了PI 3 K连接L-选择素和PSGL-1的信号通路到IL-18转录的可能性。我们首先证明了L-选择素和PSGL-1刺激上调Jurkat细胞中IL-18的转录水平。然后我们发现，PI 3 K抑制剂LY 294002减少了L-选择素和PSGL-1诱导的Jurkat细胞中IL-18 mRNA的上调。转染磷酸酶和张力蛋白同源物表达质粒可抑制IL-18的转录水平。因此，PI 3 K是启动子水平上IL-18转录激活中L-选择素和PSGL-1之间的信号连接子。据我们所知，这是第一次将PI 3 K与L-选择素和PSGL-1介导的IL-18转录直接联系起来，为PI 3 K相关炎症的干预提供了基础。
AbstractL-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) are adhesion molecules which induce similar physiological events. Our previous paper showed that phosphatidylinositol 3-kinase (PI3K) played a crucial role in L-selectin- and PSGL-1-mediated F-actin redistribution and assembly during neutrophil rolling on E-selectin. However, it is not clear whether L-selectin and PSGL-1 induce other similar physiology events by PI3K. Here, we investigated the possibility of PI3K linking the signaling pathways of L-selectin and PSGL-1 to IL-18 transcription. We first demonstrated that L-selectin and PSGL-1 stimulation upregulated IL-18 transcription level in Jurkat cells. Then we found that PI3K inhibitor LY294002 reduced L-selectin- and PSGL-1-induced mRNA upregulation of IL-18 in Jurkat cells. Transfection of phosphatase and tensin homolog expressing plasmid inhibited the transcription level of IL-18. Therefore, PI3K is a signal linker between L-selectin and PSGL-1 in IL-18 transcriptional activation at the promoter level. To our knowledge, this is the first time to directly link PI3K to L-selectin- and PSGL-1-mediated IL-18 transcription, providing a foundation for intervention of PI3K-related inflammation.