Interferon gamma induces actin polymerization, Rac1 activation and down regulates phagocytosis in human monocytic cells
Interferon gamma induces actin polymerization, Rac1 activation and down regulates phagocytosis in human monocytic cells
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DOI：
10.1016/j.cyto.2011.11.008
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发表时间：
2012-01-01
期刊：
影响因子：
3.8
通讯作者：
Ortega, Enrique
中科院分区：
文献类型：
--
作者：
Frausto-Del-Rio, Dulce;Soto-Cruz, Isabel;Ortega, Enrique
IFN γ是巨噬细胞功能的有效激活剂，IL-10是巨噬细胞功能的有效抑制剂。然而，既不是所有的细胞功能都被IFN γ增强，也不是IL-10抑制所有的细胞应答。因此。尽管IL-10和IFN γ均上调Fc γ RI表达，但IL-10处理后，单核细胞源性巨噬细胞（MDM）中Fc γ R介导的吞噬作用增加，IFN γ处理后，吞噬作用降低。在这项工作中，我们研究了IFN γ和IL-10对MDM中Fc γ R的吞噬信号传导的影响。IFN-γ处理降低IgG调理SRBC（IgG-SRBC）的吞噬作用，而IL-10处理增加其吞噬作用。这些相反的作用不能归因于每种细胞因子诱导的Fc-γ R表达的变化。由Fc γ R介导的早期生化应答明显受到细胞因子治疗的影响。IL-10处理后Syk磷酸化和[Ca 2 +]（i）的升高更高，而IFN γ处理也增加Syk磷酸化，但对[Ca 2 +]（i）的升高没有影响。IFN γ治疗导致F-肌动蛋白的基础水平增加，这种作用与IgG-SRBC和非调理剂大肠杆菌的吞噬作用降低相关。IL-10不改变F-肌动蛋白的基础水平，但增强E. coli和IgG-SRBC。IFN γ处理后达到的F-肌动蛋白水平在用IgG-SRBC或CCL 5刺激后没有进一步增加，而用IL-10处理的MDM显示出比对照细胞对CCL 5的反应略高。IFN γ增加Rac 1-GTP水平。用LY 294002抑制PI 3 K阻止IFN γ介导的肌动蛋白聚合。我们的数据表明，IFN γ诱导更高的基础水平的F-肌动蛋白和Rac 1的激活，影响对诱导细胞骨架重排的刺激，如吞噬细胞或趋化刺激的反应。(C)2011爱思唯尔有限公司保留所有权利。
IFN gamma is a potent activator and IL-10 a powerful inhibitor of macrophage functions. However, neither all cellular functions are enhanced by IFN gamma nor IL-10 inhibits all cellular responses. Thus. Fc gamma Rs-mediated phagocytosis in monocyte-derived macrophages (MDM) increases after IL-10 treatment, and decreases after treatment with IFN gamma, although both IL-10 and IFN gamma up regulate Fc gamma RI expression. In this work we investigated the effect of IFN gamma and IL-10 on phagocytic signaling by Fc gamma Rs in MDM. Treatment with IFN gamma diminished phagocytosis of IgG-opsonized SRBC (IgG-SRBC) while treatment with IL-10 increased it. These opposite effects cannot be attributed to changes in Fc gamma R expression induced by each cytokine. Early biochemical responses mediated by Fc gamma Rs were distinctly affected by cytokine treatment. Syk phosphorylation and the rise in [Ca2+](i) were higher after IL-10 treatment, whereas IFN gamma treatment also increased Syk phosphorylation but had no effect on the rise in [Ca2+](i). IFN gamma treatment led to increased basal levels of F-actin and this effect correlated with the decrease in phagocytosis of both IgG-SRBC and non-opsonized Escherichia coli. IL-10 did not alter F-actin basal levels, and enhanced the phagocytosis of E. coli and IgG-SRBC. The level of F-actin reached after IFN gamma treatment was not further increased after stimulation with IgG-SRBC or CCL5, whereas MDM treated with IL-10 showed a slightly higher response than control cells to CCL5. IFN gamma increased Rac1-GTP levels. Inhibition of PI3K with LY294002 prevented IFN gamma-mediated actin polymerization. Our data suggest that IFN gamma induces a higher basal level of F-actin and activation of Rac1, affecting the response to stimuli that induce cytoskeleton rearrangement such as phagocytic or chemotactic stimuli. (C) 2011 Elsevier Ltd. All rights reserved.