title: Suppression of nanosilica particle-induced inflammation by surface modification of the particles.
abstract: It has gradually become evident that nanomaterials, which are widely used in cosmetics, foods, and medicinal products, could induce substantial inflammation. However, the roles played by the physical characteristics of nanomaterials in inflammatory responses have not been elucidated. Here, we examined how particle size and surface modification influenced the inflammatory effects of nanosilica particles, and we investigated the mechanisms by which the particles induced inflammation. We compared the inflammatory effects of silica particles with diameters of 30-1,000 nm in vitro and in vivo. In macrophages in vitro, 30- and 70-nm nanosilica particles (nSP30 and nSP70) induced higher production of tumor necrosis factor-α (TNFα) than did larger particles. In addition, intraperitoneal injection of nSP30 and nSP70 induced stronger inflammatory responses involving cytokine production than did larger particles in mice. nSP70-induced TNFα production in macrophage depended on the production of reactive oxygen species and the activation of mitogen-activated protein kinases (MAPKs). Furthermore, nSP70-induced inflammatory responses were dramatically suppressed by surface modification of the particles with carboxyl groups in vitro and in vivo; the mechanism of the suppression involved reduction in MAPK activation. These results provide basic information that will be useful for the development of safe nanomaterials.
authors.affiliation: Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morishige
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inakura
authors.forename: Aya
authors.initials: A
authors.lastname: Tanabe
authors.forename: Shogo
authors.initials: S
authors.lastname: Narimatsu
authors.forename: Xinglei
authors.initials: X
authors.lastname: Yao
authors.forename: Youko
authors.initials: Y
authors.lastname: Monobe
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Imazawa
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mukai
authors.forename: Naoki
authors.initials: N
authors.lastname: Okada
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D053758:Nanoparticles; D010316:Particle Size; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D013499:Surface Properties; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002264:Carboxylic Acids; D018836:Inflammation Mediators; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D012822:Silicon Dioxide; D020928:Mitogen-Activated Protein Kinases