Graphene quantum dots induce apoptosis, autophagy, and inflammatory response via p38 mitogen-activated protein kinase and nuclear factor-κB mediated signaling pathways in activated THP-1 macrophages
Graphene quantum dots induce apoptosis, autophagy, and inflammatory response via p38 mitogen-activated protein kinase and nuclear factor-κB mediated signaling pathways in activated THP-1 macrophages
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DOI：
10.1016/j.tox.2014.10.011
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发表时间：
2015-01-02
期刊：
影响因子：
4.5
通讯作者：
Zhou, Shu-Feng
中科院分区：
文献类型：
--
作者：
Qin, Yiru;Zhou, Zhi-Wei;Zhou, Shu-Feng
石墨烯量子点的生物医学应用是一个新兴的领域。然而，迄今为止，其安全性数据仍然稀缺。特别是，GQD对免疫系统的影响仍然未知。本研究旨在阐明GQDs与巨噬细胞的相互作用及其机制。我们的研究结果表明，GQDs轻微影响细胞活力和膜的完整性的巨噬细胞，而GQDs显着增加活性氧（ROS）的产生和凋亡和自噬细胞死亡的Bax，Bad，caspase 3，caspase 9，Beclin 1，和LC 3-I/II的表达水平的增加和Bcl-2的减少。此外，低浓度的GQD显著增加肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1 β）、IL-8的表达，而高浓度的GQD引起对细胞因子产生的相反作用。选择性p38丝裂原活化蛋白激酶（MAPK）抑制剂SB 202190可阻断GQD对巨噬细胞的酪氨酸诱导作用。GQDs还能显著增加p38 MAPK和p65的磷酸化，促进核因子-κ B（NF-κ B）的核转位。综上所述，这些结果表明，GQD通过p38 MAPK和NF-κ B介导的信号通路在THP-1活化的巨噬细胞中诱导ROS产生、凋亡、自噬和炎症反应。(C)2014爱思唯尔爱尔兰有限公司版权所有。
The biomedical application of graphene quantum dots (GQDs) is a new emerging area. However, their safety data are still in scarcity to date. Particularly, the effect of GQDs on the immune system remains unknown. This study aimed to elucidate the interaction of GQDs with macrophages and the underlying mechanisms. Our results showed that GQDs slightly affected the cell viability and membrane integrity of macrophages, whereas GQDs significantly increased reactive oxygen species (ROS) generation and apoptotic and autophagic cell death with an increase in the expression level of Bax, Bad, caspase 3, caspase 9, beclin 1, and LC3-I/II and a decrease in that of Bcl-2. Furthermore, low concentrations of GQDs significantly increased the expression of tumor necrosis factor-a (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-8, whereas high concentrations of GQDs elicited opposite effects on the cytokines production. SB202190, a selective inhibitor of p38 mitogen-activated protein kinase (MAPK), abolished the cytokine-inducing effect of GQDs in macrophages. Moreover, GQDs significantly increased the phosphorylation of p38 MAPK and p65, and promoted the nuclear translocation of nuclear factor-kappa B (NF-kappa B). Taken together, these results show that GQDs induce ROS generation, apoptosis, autophagy, and inflammatory response via p38MAPK and NF-kappa B mediated signaling pathways in THP-1 activated macrophages. (C) 2014 Elsevier Ireland Ltd. All rights reserved.