title: 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.
abstract: 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-α (TNF-α), interleukin-1β (IL-1β), 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-κB (NF-κB). Taken together, these results show that GQDs induce ROS generation, apoptosis, autophagy, and inflammatory response via p38MAPK and NF-κB mediated signaling pathways in THP-1 activated macrophages.
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL, USA; Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL, USA.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL, USA; Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Pan
authors.affiliation: Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center & Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang 550004, Guizhou, China.
authors.forename: Zhi-Xu
authors.initials: ZX
authors.lastname: He
authors.affiliation: Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing 100083, China.
authors.forename: Xueji
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.
authors.forename: Jia-Xuan
authors.initials: JX
authors.lastname: Qiu
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria 3217, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL, USA; Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL, USA. Electronic address: szhou@health.usf.edu.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006108:Graphite / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D045663:Quantum Dots; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D006108:Graphite; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Autophagy; Graphene quantum dot; Inflammation; Nanotoxicity; Programmed cell death