Abstract
The secretion of IL-8 has been found increasing for different reasons in human bone marrow stromal cells (BMSCs), resulting in poor prognosis in patients with hematologic neoplasms. Hypoxia, a typical feature of numerous hematologic neoplasms microenvironment, often produces hypoxia inducible factor-1α (HIF-1α) which stabilizes and promotes tumor progression. Besides, hypoxic conditions also induce IL-8 production in BMSCs. However, very little is known about the mechanism of increased IL-8 expression in BMSCs caused by hypoxia. In the present study, HIF-1α and IL-8 were found highly expressed in BMSC lines under hypoxic conditions. In addition, the expression and secretion of IL-8 were significantly inhibited by the knockdown of HIF-1α under hypoxic conditions. Furthermore, HIF-1α was found to transcriptionally regulate IL-8 by binding to the region of IL-8 promoter at − 147 to − 140. Collectively, these results demonstrate that IL-8’s increase is partly due to the hypoxic microenvironment in hematologic neoplasms, and activation of HIF-1α in BMSCs contributes to the induction and transcriptional regulation of IL-8 expression.
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Funding
This work was sponsored by the National Natural Science Foundation of China (82070145), Joint Funds for the Innovation of Science and Technology, Fujian Province (2019Y9073), the government-funded project of the construction of high-level laboratory (Min201704), National Key Clinical Specialty Discipline Construction Program (2021–76), and Fujian Provincial Clinical Research Center for Hematological Malignancies (2020Y2006).
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Huang, Q., You, R., Tan, M. et al. HIF-1α is an important regulator of IL-8 expression in human bone marrow stromal cells under hypoxic microenvironment. Protoplasma 261, 543–551 (2024). https://doi.org/10.1007/s00709-023-01920-z
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DOI: https://doi.org/10.1007/s00709-023-01920-z