HIF-1α is an important regulator of IL-8 expression in human bone marrow stromal cells under hypoxic microenvironment.

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.