Lee Heewon, Lee Kyunglim
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, 120-750 Korea.
Cell Biosci. 2018 Feb 20;8:13. doi: 10.1186/s13578-018-0214-6. eCollection 2018.
Histamine releasing factor (HRF) is a unique cytokine known to regulate a variety of immune cells in late allergic reactions. In the previous study, we revealed that the biologically active form of HRF is the dimerized translationally controlled tumor protein (dTCTP) for the first time, and confirmed the secretion of IL-8 cytokine by dTCTP in human bronchial epithelial cells. However, the signaling pathway by which dTCTP promotes the secretion of IL-8 is not known.
When the cells were stimulated with dTCTP, the canonical NF-κB pathway and ERK, JNK and p38 MAPK become activated. dTCTP promoted transcription of IL-8, which involved NF-κB and AP-1 transcription factors. NF-κB was found to be essential for the transcriptional activation of IL-8, while AP-1 was partially responsible for the transcriptional activation by dTCTP. p38 MAPK was found to be involved in post-transcriptional regulation of dTCTP by stabilizing IL-8 mRNA.
This study demonstrated that dTCTP induces IL-8 secretion in BEAS-2B cells through transcriptional and post-transcriptional regulation of MAPK and NF-κB pathways. This study provides insight into the mechanism by which dTCTP induces inflammation.
组胺释放因子（HRF）是一种独特的细胞因子，已知其在迟发型过敏反应中调节多种免疫细胞。在先前的研究中，我们首次揭示了HRF的生物活性形式是二聚化的翻译控制肿瘤蛋白（dTCTP），并证实了dTCTP在人支气管上皮细胞中可分泌白细胞介素-8（IL-8）细胞因子。然而，dTCTP促进IL-8分泌的信号通路尚不清楚。
当用dTCTP刺激细胞时，经典的核因子κB（NF-κB）通路以及细胞外调节蛋白激酶（ERK）、应激活化蛋白激酶（JNK）和p38丝裂原活化蛋白激酶（p38 MAPK）被激活。dTCTP促进了IL-8的转录，这涉及NF-κB和活化蛋白-1（AP-1）转录因子。发现NF-κB对于IL-8的转录激活至关重要，而AP-1部分负责dTCTP的转录激活。发现p38 MAPK通过稳定IL-8信使核糖核酸（mRNA）参与dTCTP的转录后调控。
本研究表明，dTCTP通过对MAPK和NF-κB通路的转录和转录后调控，诱导BEAS-2B细胞中IL-8的分泌。本研究为dTCTP诱导炎症的机制提供了见解。
