IFN-γ和IL-6对多发性骨髓瘤B淋巴细胞刺激因子表达变化的调控研究

Regulation of B-lymphocyte stimulator expression levels in response to IFN-γ and IL-6

目的探讨IFN-γ和IL-6对多发性骨髓瘤（multiple myeloma，MM）B淋巴细胞刺激因子（BLyS）表达变化的影响及相关机制。方法采用流式细胞术、实时荧光定量PCR、ELISA及Western blot方法分析人MM肿瘤细胞KM3在IFN-γ和IL-6以及相关信号通路特异性抑制剂作用前后BLyS表达水平的变化。结果IFN-γ和IL-6促进KM3细胞BLyS的表达水平；NF—κB抑制剂能够抑制BLyS的表达水平；NF—κB抑制剂BAY11-7082能够完全下调IFN-γ引起的BLyS表达的上调作用；抑制促分裂原活化蛋白激酶（MAPK）的活性能够下调BLyS的表达水平。结论MAPK与NF—κB信号通路参与了BLyS的表达调节。

Objective To investigate the regulation of B-lymphocyte stimulator（BLyS） levels in response to IFN-γand IL-6. Methods Flow cytometry, quantitative polymerase chain reaction, ELISA and Western blot were applied to examine the expression level of BLyS in response to IFN-γand IL-6 . Results IFN-γ and IL-6 induced BLyS expression in KM3 cells. After treated with BAY11-7082, an IKB-α phosphorylation inhibitor, the up regulation of BLyS induced by IFN-γ was completely inhibited. Inhibiting the nuclear factor-κB （NF-κB） and mitogen activated protein kinase （MAPK） activation in KM3 cells reduced BLyS protein and gene expression. Conclusion MAPK and NF-κB pathways are involved in the regulation of BLyS expression, which suggests that MAPK and NF-κB might be used for the treatment of multiple myeloma.