Coiled-coil domain containing 3 (CCDC3) represses tumor necrosis factor-α/nuclear factor κB-induced endothelial inflammation
Coiled-coil domain containing 3 (CCDC3) represses tumor necrosis factor-α/nuclear factor κB-induced endothelial inflammation
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DOI：
10.1016/j.cellsig.2014.08.025
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发表时间：
2014-12-01
影响因子：
4.8
通讯作者：
Fu, YangXin
中科院分区：
文献类型：
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作者：
Azad, Abul Kalarn;Chakrabarti, Subhadeep;Fu, YangXin
包含卷曲螺旋结构域 3 (CCDC3) 是一种新鉴定的分泌蛋白，在血管内皮细胞 (EC) 和脂肪组织中表达。在这里，我们研究了 CCDC3 在肿瘤坏死因子 (TNF)-α 诱导的 EC 炎症反应中的作用。我们的结果表明，CCDC3 的稳定过度表达减少，而内源性 CCDC3 的稳定敲低会增加 TNF-α 诱导的 EC 中血管细胞粘附分子 1 (VCAM-1) 的 mRNA 和蛋白质水平表达。 I kappa B 激酶抑制剂 Bay 11-7082 完全阻断 TNF-α 诱导的 VCAM-1 表达，证实 EC 中 TNF-α 诱导的 VCAM-1 表达具有核因子 kappa B (NF-kappa B) 依赖性。 CCDC3 的稳定过表达会降低 TNF-α 诱导的 p65 和 p50 核易位以及 NF-κ B 转录活性，表明 CCDC3 抑制 EC 中 TNF-α 诱导的 NF-κ B 激活。与 CCDC3 过表达类似，含有 CCDC3 的条件培养基 (CM) 和纯化的 CCDC3 均降低接受 EC 中 TNF-α 诱导的 VCAM-1 表达，表明 CCDC3 具有旁分泌/自分泌功能。有趣的是，CM中的CCDC3可以进入接收EC。总而言之，我们的工作表明 CCDC3 抑制 EC 中 TNF-α/NF-κ B 诱导的促炎症反应，从而深入了解 CCDC3 的功能作用。 (C) 2014 爱思唯尔公司保留所有权利。
Coiled-coil domain containing 3 (CCDC3) is a newly identified secretory protein that is expressed in vascular endothelial cells (ECs) and adipose tissues. Here, we investigate the role of CCDC3 in tumor necrosis factor (TNF)-alpha-induced inflammatory response in ECs. Our results show that stable overexpression of CCDC3 decreases, while stable knockdown of the endogenous CCDC3 increases TNF-alpha-induced expression of vascular cell adhesion molecule-1 (VCAM-1) at the mRNA and protein level in ECs. The I kappa B kinase inhibitor Bay 11-7082 completely blocks TNF-alpha-induced expression of VCAM-1, confirming that TNF-alpha-induced expression of VCAM-1 in ECs is nuclear factor kappa B (NF-kappa B) dependent. Stable overexpression of CCDC3 decreases TNF-alpha-induced p65 and p50 nuclear translocation and NF-kappa B transcriptional activity, suggesting that CCDC3 inhibits TNF-alpha-induced NF-kappa B activation in ECs. Similar to CCDC3 overexpression, both CCDC3-containing conditioned medium (CM) and purified CCDC3 decrease TNF-a-induced expression of VCAM-1 in receiving ECs, suggesting a paracrine/autocrine function of CCDC3. Interestingly, CCDC3 in CM can enter the receiving ECs. Taken together, our work demonstrates that CCDC3 represses TNF-alpha/NF-kappa B-induced pro-inflammatory response in ECs, providing an insight into the functional role of CCDC3. (C) 2014 Elsevier Inc All rights reserved.