Abstract
Abstract
Blocking the CXCL12/CXCR4 axis can alter the biological functions of leukaemia cells. We hypothesised that two cytokines, IL-8 and IL-6, play an important role in this process. We established a co-culture model of leukaemia cells and BMSCs. When AMD3100 and G-CSF blocked the CXCL12/CXCR4 axis, biological changes in the leukaemia cells and changes in IL-8 and IL-6 concentrations were observed. We assume this regulatory process may require the participation of certain signalling pathways. After stimulating the CXCL12/CXCR4 axis, we used specific pathway blockers to determine whether four candidate signalling pathways play regulatory roles in this process. ELISA results confirmed that MG132(10 µm) inhibits the expression of IL-8, confirming that the NF/κB signalling pathway is involved. Perifosine could inhibit the expression of IL-6, confirming that the PI3K/Akt signal system is involved in this process. Western blotting confirmed that changes in the NF/κB signalling pathway resulted in the inhibition of IL-8 expression. SP600125 and Perifosine treatments also played a role. It is possible that the JNK and PI3K/AKT signalling pathways would also inhibit the expression of IL-8, but their inhibition appeared later. IL-6 expression was lower in the Perifosine group. This shows that inhibiting the PI3K/AKT signalling pathway can reduce IL-6 expression. Hence, this process requires the participation of multiple signalling pathways to jointly regulate the expression of IL-8 and IL-6. This type of regulation may be a relatively sophisticated network in which there may be cross-effects. The pathogenesis of leukaemia may be affected by this. IL-6 and IL-8 are physiologically regulated by the CXCL12/CXCR4 axis, the NF/κB and JNK/AP-1 pathways are required for IL-8 expression in T-cell acute lymphoblastic leukaemia. By upregulating IL-8, the bone marrow microenvironment and CXCL12/CXCR4 axis may contribute to the pathogenesis of T-cell acute lymphoblastic leukaemia.
Publisher
Research Square Platform LLC