CKβ8/CCL23 induces cell migration via the Gi/Go protein/PLC/PKCδ/NF-κB and is involved in inflammatory responses
CKβ8/CCL23 induces cell migration via the Gi/Go protein/PLC/PKCδ/NF-κB and is involved in inflammatory responses
复制标题
DOI：
10.1016/j.lfs.2009.11.012
复制
发表时间：
2010-02-27
期刊：
影响因子：
6.1
通讯作者：
Ko, Jesang
中科院分区：
文献类型：
--
作者：
Kim, Jeonghan;Kim, Yoon Suk;Ko, Jesang
目的：CKβ8/CCL23是一种CC趋化因子，CKβ8基因的选择性剪接产生两个编码CKβ8及其亚型CKβ8-1的mRNAs。虽然已有报道CKβ8和CKβ8-1参与了白细胞的迁移和炎症的发生，但这两种趋化因子在免疫反应和相关趋化信号中的确切作用仍不清楚。主要方法：为了了解CKβ8和CKβ8-1诱导趋化信号的机制，我们检测了表达CC趋化因子受体I的骨肉瘤细胞对CKβ8和CKβ8-1的趋化活性。我们还通过检测两种趋化因子诱导的促炎分子的mRNA表达以及这些趋化因子在泡沫细胞中的表达，验证了CKβ8和CKβ8-1在炎症反应中的作用。关键发现：使用各种信号分子抑制剂进行趋化试验的结果表明，CKβ8和CKβ8-1诱导的趋化信号通路是通过G(I)/G(O)蛋白、磷脂酶C(PLC)和蛋白激酶C增量(PKC Delta)介导的。核因子-kappa B(NF-kappa B)抑制剂可降低CK-β8和CK-β8-1的趋化活性，而核因子-kappa B可被CK-β8和CK-β8-1激活。此外，CK-β8和CK-β8-1还可增加促炎细胞因子和黏附分子的mRNA表达。这些结果表明，CKβ8和CKβ8-1均通过G(I)/G(O)蛋白、PLC、PKC Delta和核因子-kappaB传递趋化信号，CKβ8和CKβ8-1可能在动脉粥样硬化等炎症性疾病中起重要作用。(C)2009 Elsevier Inc.保留所有权利。
Aims: CK beta 8/CCL23 is a CC chemokine and alternative splicing of the CK beta 8 gene produces two mRNAs that encode CK beta 8 and its isoform CK beta 8-1. Although it has been reported that CK beta 8 and CK beta 8-1 are implicated in leukocyte trafficking and development of inflammation, the exact roles of these two chemokines in immune responses and the associated chemotaxis signaling are still obscure.Main methods: To understand the mechanism of CK beta 8- and CK beta 8-1-induced chemotaxis signaling, we examined the chemotactic activities of osteogenic sarcoma cells expressing CC chemokine receptor I in response to CK beta 8 and CK beta 8-1. We also examined involvement of CK beta 8 and CK beta 8-1 in inflammatory responses by determining the mRNA expression of pro-inflammatory molecules induced by two chemokines and expressions of these chemokines in foam cells.Key findings: Results from a chemotaxis assay using various inhibitors for signaling molecules showed that the chemotaxis signal pathway induced by both CK beta 8 and CK beta 8-1 was mediated via the G(i)/G(o) protein, phospholipase C (PLC) and protein kinase C delta (PKC delta). Treatment with a nuclear factor kappa B (NF-kappa B) inhibitor reduced the chemotactic activities of CK beta 8 and CK beta 8-1, and NF-kappa B was activated in response to CK beta 8 and CK beta 8-1. In addition, CK beta 8 and CK beta 8-1 increased mRNA expression of pro-inflammatory cytokines and adhesion molecules. The mRNA levels of CK beta 8 and CK beta 8-1 were increased in foam cells.Significance: These results indicate that both CK beta 8 and CK beta 8-1 transduce the chemotaxis signal through the G(i)/G(o) protein, PLC, PKC delta, and NF-kappa B, and that CK beta 8 and CK beta 8-1 probably play important roles in inflammatory diseases such as atherosclerosis. (C) 2009 Elsevier Inc. All rights reserved.