STAT信号通路对小鼠脾脏MDSC极化状态的影响

The effect of STAT signaling pathway on MDSC polarization

利用B16F10荷瘤小鼠诱导髓源性抑制细胞(MDSC)的产生,磁珠分选小鼠脾脏中的MDSC,体外用相应的细胞因子刺激后,提取其总蛋白质,Western blot方法检测转录激活因子(STAT)通路的活化情况,并利用STAT通路抑制剂,ELISA方法检测代表MDSC极化状态的IL-10和TNF-α的分泌情况,探讨STAT通路在小鼠MDSC极化状态中的作用。结果表明:抑制STAT3活化使MDSC中I型精氨酸酶活性降低,TNF-α分泌水平升高;抑制STAT6活化使MDSC分泌IL-10水平下降,TNF-α水平升高;抑制NF-κB活化使MDSC分泌IL-10水平下降,但对TNF-α没有明显影响;抑制STAT1活化对MDSC分泌IL-10和TNF-α没有明显影响,推测STAT3和STAT6信号通路在MDSC的极化中发挥着重要作用。

MDSCs were isolated from erythrocyte-depleted splenocytes in B16 F10-bearing mice using anti-mouse CD11 b beads. The sorted MDSCs were stimulated with cytokines and the phosphorylation of STAT signaling pathway was detected by Western blot. STAT inhibitors were used to study the signaling pathways for the induced of IL-10 and TNF-α production. In this study, STAT3 and STAT6 inhibitor inhibited arginase activity or IL-10 production, while increased TNF-α production in MDSC;NF-κB inhibitor inhibited IL-10 production in MDSC;STAT1 inhibitor had no effect on IL-10 and TNF-α production in MDSC. We speculated that STAT3 and STAT6 signaling pathway were involved in the MDSC polarization.