title: Immunotoxicity of zinc oxide nanoparticles with different size and electrostatic charge.
abstract: While zinc oxide (ZnO) nanoparticles (NPs) have been recognized to have promising applications in biomedicine, their immunotoxicity has been inconsistent and even contradictory. To address this issue, we investigated whether ZnO NPs with different size (20 or 100 nm) and electrostatic charge (positive or negative) would cause immunotoxicity in vitro and in vivo, and explored their underlying molecular mechanism. Using Raw 264.7 cell line, we examined the immunotoxicity mechanism of ZnO NPs as cell viability. We found that in a cell viability assay, ZnO NPs with different size and charge could induce differential cytotoxicity to Raw 264.7 cells. Specifically, the positively charged ZnO NPs exerted higher cytotoxicity than the negatively charged ones. Next, to gauge systemic immunotoxicity, we assessed immune responses of C57BL/6 mice after oral administration of 750 mg/kg/day dose of ZnO NPs for 2 weeks. In parallel, ZnO NPs did not alter the cell-mediated immune response in mice but suppressed innate immunity such as natural killer cell activity. The CD4(+)/CD8(+) ratio, a marker for matured T-cells was slightly reduced, which implies the alteration of immune status induced by ZnO NPs. Accordingly, nitric oxide production from splenocyte culture supernatant in ZnO NP-fed mice was lower than control. Consistently, serum levels of pro/anti-inflammatory (interleukin [IL]-1β, tumor necrosis factor-α, and IL-10) and T helper-1 cytokines (interferon-γ and IL-12p70) in ZnO NP-fed mice were significantly suppressed. Collectively, our results indicate that different sized and charged ZnO NPs would cause in vitro and in vivo immunotoxicity, of which nature is an immunosuppression.
authors.affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.
authors.forename: Cheol-Su
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.
authors.forename: Hai-Duong
authors.initials: HD
authors.lastname: Nguyen
authors.affiliation: Department of Environmental Medical Biology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.
authors.forename: Rosa Mistica
authors.initials: RM
authors.lastname: Ignacio
authors.affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.
authors.forename: Hyeon-Cheol
authors.initials: HC
authors.lastname: Cho
authors.affiliation: Healthcare Laboratory, Medical Device Evaluation Team, Korea Testing and Research Institute, Gimpo-si, Gyeonggi-do, Republic of Korea.
authors.forename: Eun Ho
authors.initials: EH
authors.lastname: Maeng
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical School and College, Korea University, Seoul, Republic of Korea.
authors.forename: Yu-Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical School and College, Korea University, Seoul, Republic of Korea.
authors.forename: Meyoung-Kon
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.
authors.forename: Bae-Keun
authors.initials: BK
authors.lastname: Park
authors.affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea ; Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.
authors.forename: Soo-Ki
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D055672:Static Electricity; D018675:Toxicity Tests; D015034:Zinc Oxide / Q000737:chemistry / Q000633:toxicity
chemical_list: D016207:Cytokines; D015034:Zinc Oxide
keywords: ZnO; cytokine; cytotoxicity; immune response; immunosuppression; innate immunity