Multi-walled carbon nanotubes (MWCNTs) promoted lipid accumulation in THP-1 macrophages through modulation of endoplasmic reticulum (ER) stress

Abstract

Recent studies from us and others have shown that nanoparticle (NP) exposure could modulate endoplasmic reticulum (ER) stress. Since ER stress is closely related to lipid droplet biogenesis, in this study, we investigated if multi-walled carbon nanotubes (MWCNTs) might influence lipid accumulation in THP-1 macrophages through the modulation of ER stress. Exposure to up to 64 μg/mL pristine MWCNTs (p-MWCNTs), hydroxylated MWCNTs (h-MWCNTs), and carboxylated MWCNTs (c-MWCNTs) led to NP internalization, which was associated with a modest increase of cytotoxicity. Oxidative stress was also induced, showing as increased intracellular reactive oxygen species (ROS) and decreased glutathione. Only h-MWCNTs and c-MWCNTs significantly promoted the release of interleukin-8 (IL-8), which was significantly higher compared with that after p-MWCNT exposure. All types of MWCNTs significantly induced lipid accumulation in THP-1 macrophages and more modestly in the co-culture model consisting of 16HBE human bronchial epithelial cells and THP-1 macrophages. MWCNT-induced lipid accumulation in THP-1 macrophages was decreased modestly by antioxidant N-acetyl-l-cysteine and more effectively by ER stress inhibitor 4-phenylbutyric acid. Moreover, MWCNT exposure promoted the expression of ER stress gene DDIT3 as well as ER stress protein p-chop, whereas the transcription factor XBP-1s was decreased. In addition, the expression of scavenger receptors, namely CD36 and MSR1, was also elevated after MWCNT exposure. In conclusion, this study suggested that MWCNT exposure could promote lipid accumulation in THP-1 macrophages, which could be related to the modulation of ER stress leading to upregulation of scavenger receptors.