The roles of MCP-1 and protein kinase Cδ activation in human eosinophilic leukemia EoL-1 cells
The roles of MCP-1 and protein kinase Cδ activation in human eosinophilic leukemia EoL-1 cells
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DOI：
10.1016/j.cyto.2009.07.008
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发表时间：
2009-12-01
期刊：
影响因子：
3.8
通讯作者：
Kim, In Sik
中科院分区：
文献类型：
--
作者：
Lee, Ji-Sook;Yang, Eun Ju;Kim, In Sik
特发性嗜酸性粒细胞增多综合征是一种与克隆性嗜酸性粒细胞增生相关的疾病。FIP 1-like-1-platelet-derived growth factor receptor-alpha（FIP 1 L1-PDGFRA）在HES的发病机制和分类中的重要性最近已有报道。在这项研究中，我们研究了单核细胞趋化蛋白-1（MCP-1）/CCL 2对人嗜酸性白血病细胞系EoL-1的趋化活性和蛋白激酶C δ（PKC δ）的贡献。这些细胞在CC趋化因子受体（CCR 1 -5）中表达CCR 2蛋白。MCP-1诱导EoL-1细胞的强烈迁移，并且响应于MCP-1的趋化信号涉及G（i）/G（o）蛋白、磷脂酶C（PLC）、PKC δ、p38 MAPK和NF-κ B。MCP-1通过G（i）/G（o）蛋白、PLC和PKC δ级联激活p38 MAN。MCP-1还诱导NF-κ B易位，并且该活化被PKC δ活化抑制。与正常嗜酸性粒细胞相比，EoL-1细胞中PKC δ的基础表达和活性的增加抑制了EoL-1细胞的凋亡。PKC δ的抗凋亡机制与caspase 3和caspase 9的抑制有关，而与FIP 1 L1-PDGFRA无关。PKC δ作为抗凋亡分子发挥作用，并参与MCP-1刺激的EoL-1细胞运动。本研究有助于了解MCP-1在嗜酸性粒细胞生物学中的作用以及嗜酸性粒细胞疾病的发病机制。(C)2009爱思唯尔有限公司保留所有权利。
Idiopathic hypereosinophilc syndrome is a disorder associated with clonally eosinophilic proliferation. The importance of FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) in the pathogenesis and classification of HES has been recently reported. In this study, we investigated the contribution of monocyte chemoattractant protein-1 (MCP-1)/CCL2 to chemotactic activity and protein kinase C delta (PKC delta in the human eosinophilic leukemia cell line EoL-1. These cells express CCR2 protein among the CC chemokine receptors (CCR1-5). MCP-1 induces strong migration of EoL-1 cells and the chemotaxis signal in response to MCP-1 involves a G(i)/G(o) protein, phospholipase C (PLC), PKC delta, p38 MAPK and NF-kappa B. MCP-1 activates p38 MAN via G(i)/G(o) protein, PLC and PKC delta cascade. MCP-1 also induces NF-kappa B translocation and the activation is inhibited by PKC delta activation. The increase in the basal expression and activity of PKC delta in EoL-1 cells, compared to normal eosinophils, inhibits apoptosis in EoL-1 cells. Anti-apoptotic mechanism of PKC delta is related to inhibition of caspase 3 and caspase 9, but not to FIP1L1-PDGFRA. PKC delta functions as an anti-apoptotic molecule, and is involved in EoL-1 cell movement stimulated by MCP-1. This study contributes to an understanding of MCP-1 in eosinophil biology and pathogenic mechanism of eosinophilic disorders. (C) 2009 Elsevier Ltd. All rights reserved.