IL-6 Upregulates CD73 in Human Placental Mesenchymal Stem Cells to Promote ATRA-Induced NB4 Cell Differentiation in Acute Promyelocytic Leukemia.
To investigate the expression profile of IL-6 in patients with acute promyelocytic leukemia (APL) and its role in modulating the ability of hPMSCs to regulate the differentiation of NB4 cells.
Peripheral blood samples were obtained from newly diagnosed APL patients and healthy controls. IL-6 levels were measured using flow cytometry-based (FCM) multiplex immunoassays. A co-culture system of hPMSCs and NB4 cells was established. The effects of hPMSCs on ATRA-induced differentiation, proliferation, and phagocytic activity of NB4 cells were evaluated by Wright-Giemsa staining, FCM, CCK-8 assays, and phagocytosis assays. Western blot analysis was performed to investigate the signaling mechanisms by which IL-6 regulates CD73 expression in hPMSCs. To determine whether the regulatory effects of hPMSCs are mediated by CD73, interventions using a CD73 inhibitor and CD73-knockdown hPMSCs were conducted.
IL-6 levels were significantly elevated in the peripheral blood of APL patients and showed a positive correlation with both risk stratification and the severity of retinoic acid syndrome (RAS). hPMSCs enhanced ATRA-induced differentiation of NB4 cells while suppressing their proliferation and phagocytic function. Moreover, inhibition or knockdown of CD73 markedly attenuated the pro-differentiation effect of hPMSCs on NB4 cells. NB4 cells exhibited high surface expression of adenosine receptors. IL-6 was found to upregulate CD73 expression in hPMSCs through activation of the PI3K/AKT signaling pathway.
IL-6 enhances the pro-differentiation capacity of hPMSCs toward NB4 cells by upregulating CD73 expression, offering a potential new strategy for the clinical treatment of APL.
Peripheral blood samples were obtained from newly diagnosed APL patients and healthy controls. IL-6 levels were measured using flow cytometry-based (FCM) multiplex immunoassays. A co-culture system of hPMSCs and NB4 cells was established. The effects of hPMSCs on ATRA-induced differentiation, proliferation, and phagocytic activity of NB4 cells were evaluated by Wright-Giemsa staining, FCM, CCK-8 assays, and phagocytosis assays. Western blot analysis was performed to investigate the signaling mechanisms by which IL-6 regulates CD73 expression in hPMSCs. To determine whether the regulatory effects of hPMSCs are mediated by CD73, interventions using a CD73 inhibitor and CD73-knockdown hPMSCs were conducted.
IL-6 levels were significantly elevated in the peripheral blood of APL patients and showed a positive correlation with both risk stratification and the severity of retinoic acid syndrome (RAS). hPMSCs enhanced ATRA-induced differentiation of NB4 cells while suppressing their proliferation and phagocytic function. Moreover, inhibition or knockdown of CD73 markedly attenuated the pro-differentiation effect of hPMSCs on NB4 cells. NB4 cells exhibited high surface expression of adenosine receptors. IL-6 was found to upregulate CD73 expression in hPMSCs through activation of the PI3K/AKT signaling pathway.
IL-6 enhances the pro-differentiation capacity of hPMSCs toward NB4 cells by upregulating CD73 expression, offering a potential new strategy for the clinical treatment of APL.