Interleukin-10-induced CCR5 expression in macrophage like HL-60 cells: Involvement of Erk1/2 and STAT-3
Interleukin-10-induced CCR5 expression in macrophage like HL-60 cells: Involvement of Erk1/2 and STAT-3
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DOI：
10.1248/bpb.26.1076
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发表时间：
2003-08-01
影响因子：
2
通讯作者：
Kasahara, T
中科院分区：
文献类型：
--
作者：
Makuta, Y;Sonoda, Y;Kasahara, T
IL-10 是一种免疫抑制和抗炎细胞因子，最近据报道在人单核细胞的 CCR5 表达中发挥作用。 CCR5 启动子区域包含 Oct-2、TCF-1α GATA 和 STAT 结合位点。在这里，我们使用 HL-60 细胞系研究了 IL-10 刺激的细胞中参与 CCR5 表达的信号。用PMA刺激HL-60细胞并分化为巨噬细胞样细胞，然后用IL-10刺激。 IL-10 诱导这些细胞中 CCR5 蛋白和 CCR5 mRNA 的显着表达。 MEK-1 抑制剂 PD98059 抑制 IL-10 对 CCR5 的诱导。此外，IL-10 诱导 Erk 的酪氨酸 (Tyr) 磷酸化，以及 STAT-3 的丝氨酸 (Ser) 和 Tyr 磷酸化。 PD98059 抑制 Erk 的 Tyr 磷酸化和 STAT-3 的 Ser 磷酸化，而 PD98059 不抑制 STAT-3 的 Tyr 磷酸化。通过IL-10刺激观察STAT-3的DNA结合活性，该活性被PD98059抑制。这些结果首先表明 Erk1/2 和 STAT-3 调节 CCR5 表达，并且 Erk 介导的 Ser 磷酸化是完全刺激 CCR5 表达中 STAT-3 所必需的。
an immunosuppressive and anti-inflammatory cytokine, IL-10 was recently reported to play roles in CCR5 expression in human monocytes. CCR5 promoter regions contain Oct-2, TCF-1alpha GATA, and STAT binding sites. Here, we studied the signals involved in the CCR5 expression in IL-10-stimulated cells using the HL-60 cell line. HL-60 cells were stimulated with PMA and differentiated to macrophage-like cells, then stimulated with IL-10. IL-10 induced significant expression of CCR5 protein and CCR5 mRNA in these cells. The induction of CCR5 by IL-10 was inhibited by a MEK-1 inhibitor, PD98059. In addition, IL-10 induced tyrosine (Tyr) phosphorylation of Erk, as well as serine (Ser) and Tyr phosphorylation of STAT-3. Tyr phosphorylation of Erk and Ser phosphorylation of STAT-3 were inhibited by PD98059, while Tyr phosphorylation of STAT-3 was not inhibited by PD98059. DNA binding activity of STAT-3 was observed by the stimulation with IL-10, which was inhibited by PD98059. These results first indicate that Erk1/2 and STAT-3 regulate CCR5 expression, and that Erk-mediated phosphorylation of Ser is required for full stimulation of STAT-3 in CCR5 expression.