Cytotoxicity, cytokine release and ER stress-autophagy gene expression in endothelial cells and alveolar-endothelial co-culture exposed to pristine and carboxylated multi-walled carbon nanotubes
Cytotoxicity, cytokine release and ER stress-autophagy gene expression in endothelial cells and alveolar-endothelial co-culture exposed to pristine and carboxylated multi-walled carbon nanotubes
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暴露于原始和羧化多壁碳纳米管的内皮细胞和肺泡内皮共培养物中的细胞毒性、细胞因子释放和内质网应激自噬基因表达
DOI：
10.1016/j.ecoenv.2018.06.025
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发表时间：
2018-10-15
影响因子：
6.8
通讯作者：
Cao, Yi
中科院分区：
文献类型：
--
作者：
Chang, Shiwei;Zhao, Xuqi;Cao, Yi
近年来，我们发现多壁碳纳米管（MWCNTs）直接作用于人脐静脉内皮细胞（HUVECs）可能通过调节内质网应激基因的表达而引起细胞毒性反应，但这种信号是否能从其他细胞传递到内皮细胞（ECs）尚不清楚。本研究探讨了原始的和羧基化的多壁碳纳米管对HUVECs和肺泡-内皮细胞共培养的毒性，后者可以模拟EC和多壁碳纳米管暴露的肺泡细胞之间可能的信号通信。结果表明，与高水平的多壁碳纳米管直接接触诱导细胞毒性，并调节与ER应激（HSPA 5，DDIT 3和XBP-1 s）和自噬（BECN 1和ATG 12）相关的基因的表达在上室培养的A549-THP-1巨噬细胞以及HUVEC中。然而，大多数这些反应是最小的或可忽略不计的HUVEC培养在较低的腔室。此外，仅在暴露于MWCNT的HUVEC中观察到细胞因子释放（白细胞介素-6和可溶性血管细胞粘附分子-1）显著增加（p < 0.01），而在下室培养的HUVEC中未观察到（p > 0.05）。最小或甚至没有反应可能是由于MWCNT从上室到下室的相对低的移位，而在上室中培养的A549-巨噬细胞内化了大量MWCNT。结果表明，ER应激自噬信号可能无法从肺泡细胞转移到内皮细胞，除非有足够的多壁碳纳米管易位。
Recently we found that direct exposure of human umbilical vein endothelial cells (HUVECs) to multi-walled carbon nanotubes (MWCNTs) might induce toxicological responses through the modulation of ER stress gene expression, but whether this signal could be transferred from other cells to endothelial cells (ECs) is unknown. This study investigated the toxicity of pristine and carboxylated MWCNTs to HUVECs and alveolar-endothelial co-culture, the later of which could mimic the possible signaling communications between ECs and MWCNT exposed alveolar cells. The results showed that direct contact with high levels of MWCNTs induced cytotoxicity and modulated expression of genes associated with ER stress (HSPA5, DDIT3 and XBP-1s) and autophagy (BECN1 and ATG12) both in A549-THP-1 macrophages cultured in the upper chambers as well as HUVECs. However, most of these responses were minimal or negligible in HUVECs cultured in the lower chambers. Moreover, significantly increased cytokine release (interleukin-6 and soluble vascular cell adhesion molecule-1) was only observed in MWCNT exposed HUVECs (p < 0.01) but not HUVECs cultured in the lower chambers (p > 0.05). The minimal or even absent response was likely due to relatively low translocation of MWCNTs from upper chambers to lower chambers, whereas A549-macrophages cultured in the upper chambers internalized large amount MWCNTs. The results indicated that ER stress-autophagy signaling might not be able to transfer from alveolar cells to endothelial cells unless sufficient MWCNTs are translocated.