Background: 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. Results: 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 foundto be involved in post-transcriptional regulation of dTCTP by stabilizing IL-8 mRNA. Conclusions: 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.
Bibliographical noteFunding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (2017R1A2B2004023) and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C0631).
© 2018 The Author(s).
- Dimerized TCTP