title: Pro-inflammatory responses of RAW264.7 macrophages when treated with ultralow concentrations of silver, titanium dioxide, and zinc oxide nanoparticles.
abstract: To cellular systems, nanoparticles are considered as foreign particles. Upon particles and cells contact, innate immune system responds by activating the inflammatory pathway. However, excessive inflammation had been linked to various diseases ranging from allergic responses to cancer. Common nanoparticles, namely silver, titanium dioxide, and zinc oxide exist in the environment as well as in consumer products at ultralow level of 10(-6)-10(-3) μg mL(-1). However, so far the risks of such low NPs concentrations remain unexplored. Therefore, we attempted to screen the pro-inflammatory responses after ultralow concentration treatments of the three nanoparticles on RAW264.7 macrophages, which are a part of the immune system, at both cellular and gene levels. Even though cytotoxicity was only observed at nanoparticles concentrations as high as 10 μg mL(-1), through the level of NF-κB and upregulation of pro-inflammatory genes, we observed activation of the induction of genes encoding pro-inflammatory cytokines starting already at 10(-7) μg mL(-1). This calls for more thorough characterization of nanoparticles in the environment as well as in consumer products to ascertain the health and safety of the consumers and living systems in general.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
authors.forename: Marcella
authors.initials: M
authors.lastname: Giovanni
authors.affiliation: PUB, 40 Scotts Road, Singapore 228231, Singapore.
authors.forename: Junqi
authors.initials: J
authors.lastname: Yue
authors.affiliation: PUB, 40 Scotts Road, Singapore 228231, Singapore.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, Singapore 117549, Singapore; NUS Environmental Research Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore.
authors.forename: Choon Nam
authors.initials: CN
authors.lastname: Ong
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore. Electronic address: cheltwd@nus.edu.sg.
authors.forename: David Tai
authors.initials: DT
authors.lastname: Leong
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000235:genetics; D053758:Nanoparticles / Q000737:chemistry*; D012834:Silver / Q000737:chemistry / Q000633:toxicity*; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*; D014162:Transfection; D015034:Zinc Oxide / Q000737:chemistry / Q000633:toxicity*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; C009495:titanium dioxide; D012834:Silver; D014025:Titanium; D015034:Zinc Oxide
keywords: Nanoparticles; Pro-inflammatory response; RAW264.7