title: Cytotoxic and Proinflammatory Effects of Metal-Based Nanoparticles on THP-1 Monocytes Characterized by Combined Proteomics Approaches.
abstract: Thorough characterization of toxic effects of nanoparticles (NP) is desirable due to the increasing risk of potential environmental contamination by NP. In the current study, we combined three recently developed proteomics approaches to assess the effects of Au, CuO, and CdTe NP on the innate immune system. The human monocyte cell line THP-1 was employed as a model. The anticancer drugs camptothecin and doxorubicin were used as positive controls for cell death, and lipopolysaccharide was chosen as a positive control for proinflammatory activation. Despite equivalent overall toxicity effect (50 ± 10% dead cells), the three NP induced distinctly different proteomics signatures, with the strongest effect being induced by CdTe NP, followed by CuO and gold NP. The CdTe toxicity mechanism involves down-regulation of topoisomerases. The effect of CuO NP is most reminiscent of oxidative stress and involves up-regulation of proteins involved in heat response. The gold NP induced up-regulation of the inflammatory mediator, NF-κB, and its inhibitor TIPE2 was identified as a direct target of gold NP. Furthermore, gold NP triggered activation of NF-κB as evidenced by phosphorylation of the p65 subunit. Overall, the combined proteomics approach described here can be used to characterize the effects of NP on immune cells.
authors.forename: Nataliya K
authors.identifier: 0000-0002-5816-277X
authors.initials: NK
authors.lastname: Tarasova
authors.forename: Audrey
authors.initials: A
authors.lastname: Gallud
authors.forename: A Jimmy
authors.initials: AJ
authors.lastname: Ytterberg
authors.forename: Alexey
authors.initials: A
authors.lastname: Chernobrovkin
authors.affiliation: Université de Bordeaux 1, CNRS UMR , 5255 Talence, France.
authors.forename: Jaime Ruiz
authors.initials: JR
authors.lastname: Aranzaes
authors.affiliation: Université de Bordeaux 1, CNRS UMR , 5255 Talence, France.
authors.forename: Didier
authors.identifier: 0000-0001-6446-8751
authors.initials: D
authors.lastname: Astruc
authors.affiliation: PlasmaChem GmbH, Rudower Chaussee 29, D-12489 Berlin, Germany.
authors.forename: Alexei
authors.initials: A
authors.lastname: Antipov
authors.affiliation: PlasmaChem GmbH, Rudower Chaussee 29, D-12489 Berlin, Germany.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fedutik
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
authors.forename: Roman A
authors.initials: RA
authors.lastname: Zubarev
mesh_terms: D019187:Cadmium Compounds / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000009:adverse effects; D003603:Cytotoxins / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage; D006046:Gold / Q000009:adverse effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D053768:Metal Nanoparticles / Q000009:adverse effects*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020543:Proteome / Q000187:drug effects / Q000235:genetics*; D040901:Proteomics; D013691:Tellurium / Q000009:adverse effects
chemical_list: D019187:Cadmium Compounds; D003603:Cytotoxins; D008070:Lipopolysaccharides; D020543:Proteome; D006046:Gold; D003300:Copper; D004317:Doxorubicin; D013691:Tellurium; C028337:cadmium telluride; C030973:cupric oxide; D002166:Camptothecin
keywords: Nanomaterials; anticancer drugs; copper oxide; gold nanoparticles; inflammation; monocyte assay; quantum dots; thermal proteome profiling