title: Reaction of human macrophages on protein corona covered TiO₂ nanoparticles.
abstract: The cytokine secretion of primary cells of human macrophages during the interaction of TiO2 nanoparticles (with an average primary size of 100-120 nm) is investigated down to concentration levels suggested to be relevant for in vivo conditions. We find that high TiO2 concentrations induce the cytokines Interleukin IL-1β, IL-6, and IL-10 secretion, while at low concentrations only IL-6 secretion is observed. To obtain further evidence on in vivo conditions we investigated the development and structure of the protein corona of the nanoparticles. We demonstrated that the surface of TiO2 particles attract preferably secondary modified proteins which then induce cytokine secretion of macrophages. Our results indicate that concentration of corona covered TiO2 particles below 1 μg/ml induce IL-6 secretion which is reported to be responsible for the development of autoimmune diseases as well as for the secretion of acute phase proteins.
  
  
  BACKGROUND
  This study investigates the effects of protein corona covered titanium dioxide nanoparticles on human macrophages, concluding that concentration of such particles below 1 μg/ml induces IL-6 secretion, which may be responsible for the development of autoimmune diseases as well as for the secretion of acute phase proteins. This finding has important implications on future applications of such nanoparticles.
authors.affiliation: Center for Nanotechnology (CeNTech) and Physical Institute, University of Münster, Münster, Germany. Electronic address: borgognc@uni-muenster.de.
authors.forename: Camila F
authors.initials: CF
authors.lastname: Borgognoni
authors.affiliation: Institute for Hygiene, University of Münster, Münster, Germany. Electronic address: mmormann@uni-muenster.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Mormann
authors.affiliation: Center for Nanotechnology (CeNTech) and Physical Institute, University of Münster, Münster, Germany; Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing, P. R. China. Electronic address: quy@nanoctr.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.affiliation: nanoAnalytics GmbH, Münster, Germany. Electronic address: M.Schaefer@nanoanalytics.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schäfer
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Münster, Germany. Electronic address: k.langer@uni-muenster.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Langer
authors.affiliation: Chemicell GmbH, Berlin, Germany. Electronic address: info@chemicell.com.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Öztürk
authors.affiliation: Fraunhofer-Institut für Biomedizinische Technik IBMT St. Ingbert, Germany. Electronic address: sylvia.wagner@ibmt.fraunhofer.de.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing, P. R. China. Electronic address: chenchy@nanoctr.cn.
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
authors.affiliation: Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing, P. R. China. Electronic address: zhaoyuliang@ihep.ac.cn.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Center for Nanotechnology (CeNTech) and Physical Institute, University of Münster, Münster, Germany. Electronic address: fuchsh@uni-muenster.de.
authors.forename: Harald
authors.initials: H
authors.lastname: Fuchs
authors.affiliation: Center for Nanotechnology (CeNTech) and Physical Institute, University of Münster, Münster, Germany. Electronic address: K.Riehemann@uni-muenster.de.
authors.forename: Kristina
authors.initials: K
authors.lastname: Riehemann
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D016209:Interleukin-8 / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D014025:Titanium / Q000008:administration & dosage* / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D053583:Interleukin-1beta; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C009495:titanium dioxide; D014025:Titanium
keywords: Human macrophage; Immunology; Interleukin-6; Nanoparticles; Nanotoxicology; Protein corona; Titanium dioxide