title: Silica nanoparticles induce oxidative stress and inflammation of human peripheral blood mononuclear cells.
abstract: In the present study, the effects of 10- or 100-nm silica oxide (SiO2) NPs on human peripheral blood mononuclear cells (PBMC) were examined. Cytotoxic effects and oxidative stress effects, including glutathione (GSH) depletion, the formation of protein radical species, and pro-inflammatory cytokine responses, were measured. PBMC exposed to 10-nm NP concentrations from 50 to 4,000 ppm showed concentration-response increases in cell death; whereas, for 100-nm NPs, PBMC viability was not lost at <500 ppm. Interestingly, 10-nm NPs were more cytotoxic and induced more oxidative stress than 100-nm NPs. Immunoelectron micrographs show the cellular distribution of GSH and NPs. As expected based on the viability data, the 10-nm NPs disturbed cell morphology to a greater extent than did the 100-nm NPs. Antibody to the radical scavenger, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), was used for Western blot analysis of proteins with radicals; more DMPO proteins were found after exposure to 10-nm NPs than 100-nm NPs. Examination of cytokines (TNF-α, IL-1ra, IL-6, IL-8, IL-1β, and IFN-γ) indicated that different ratios of cytokines were expressed and released after exposure to 10- and 100-nm NPs. IL-1β production was enhanced by 10- and 100-nm NPs;, the cytotoxicity of the NPs was associated with an increase in the IL-1β/IL-6 ratio and 100-nm NPs at concentrations that did not induce loss of cell viability enhanced IL-1β and IL-6 to an extent similar to phytohemagglutinin (PHA), a T cell mitogen. In conclusion, our results indicate that SiO2 NPs trigger a cytokine inflammatory response and induce oxidative stress in vitro, and NPs of the same chemistry, but of different sizes, demonstrate differences in their intracellular distribution and immunomodulatory properties, especially with regard to IL-1β and IL-6 expression.
authors.affiliation: Wadsworth Center, New York State Department of Health, Center for Medical Sciences, 150 New Scotland Avenue, Albany, NY, 12208, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mendoza
authors.forename: Jose A
authors.initials: JA
authors.lastname: Torres-Hernandez
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Ault
authors.forename: Joan H
authors.initials: JH
authors.lastname: Pedersen-Lane
authors.forename: Donghong
authors.initials: D
authors.lastname: Gao
authors.forename: David A
authors.initials: DA
authors.lastname: Lawrence
mesh_terms: D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D053758:Nanoparticles; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D018836:Inflammation Mediators; D016877:Oxidants; D012822:Silicon Dioxide; D005978:Glutathione