title: Size-dependent effect of zinc oxide on toxicity and inflammatory potential of human monocytes.
abstract: With the rapid development of nanomedicines, it is important to understand their potential immunotoxicity. Zinc oxide (ZnO) nanoparticles have several applications in the pharmaceutical and biomedicine industries. This study investigates the effect of particles size (nano and micro) of ZnO on viability, phagocytosis, and cytokine induction in human monocytes, THP-1 cells, a model of the innate immune system. Cells were incubated with nano (approximately 100 nm) and micro (approximately 5 μm) sized ZnO particles in a concentration range of 10-100 μg/ml. The parameters measured included the MTT assay, phagocytosis assay, enzyme-linked immunosorbent assay (ELISA), gene expression, and DNA analysis. ZnO particles significantly decreased cell viability in a size- and concentration-dependent manner associated with significant alterations in phagocytic capacity of monocytes. Exposure of THP-1 cells to both sizes of ZnO stimulated and increased release of proinflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6, as well as chemokine IL-8, and upregulated the expression of monocyte chemoattractant protein-1 and cyclooxygenase-2 genes. However, ZnO particles did not markedly affect monocytes DNA. Collectively, these results suggest higher propensity of nano ZnO particles in inducing cytotoxicity and inflammation in human monocytes regardless of micro size, and caution needs to be taken concerning their biological application.
authors.affiliation: a Pharmacology and Toxicology Division , Defence Research and Development Establishment , Jhansi Road , Gwalior , India.
authors.forename: Devashri
authors.initials: D
authors.lastname: Sahu
authors.forename: G M
authors.initials: GM
authors.lastname: Kannan
authors.forename: R
authors.initials: R
authors.lastname: Vijayaraghavan
mesh_terms: D002460:Cell Line; D002470:Cell Survival; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007700:Kinetics; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D008863:Microspheres; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009153:Mutagens / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D013499:Surface Properties; D015854:Up-Regulation / Q000187:drug effects*; D015034:Zinc Oxide / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D009153:Mutagens; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015034:Zinc Oxide