title: Copper oxide nanoparticles recruit macrophages and modulate nitric oxide, proinflammatory cytokines and PGE2 production through arginase activation.
abstract: In the present study, we examine the effects of copper oxide nanoparticles (CuNP) on macrophage immune response and the signaling pathways involved.
  
  
  
  A peritonitis model was used to determine in vivo immune cells recruitment, while primary macrophages were used as an in vitro model for the cellular and molecular analysis.
  
  
  
  In vivo, CuNP induce significant macrophages recruitment to the site of injection. In vitro, in LPS-stimulated primary macrophages, the co-treatment with CuNP inhibited the production of NO in a dose-dependent manner. The mechanism underlying NO and proinflammatory cytokines inhibition was associated with an increased arginase activity. Macrophage stimulation with CuNP did not provoke any cytokine secretion; however, arginase inhibition promoted TNFα and MIP-1β production. In addition, CuNP induced the expression of COX-2 and the production of PGE2 through arginase activation.
  
  
  
  Our results demonstrate that CuNP activate arginase and suppress macrophage innate immune response.
authors.affiliation: Investigación y Desarrollo, Fundación Ciencia y Tecnología para el Desarrollo, Santiago, Chile.|Investigación y Desarrollo, Laboratorio Centrovet, Santiago, Chile.
authors.forename: Sergio
authors.initials: S
authors.lastname: Arancibia
authors.affiliation: Investigación y Desarrollo, Laboratorio Centrovet, Santiago, Chile.
authors.forename: Andrea
authors.initials: A
authors.lastname: Barrientos
authors.affiliation: Investigación y Desarrollo, Laboratorio Centrovet, Santiago, Chile.
authors.forename: Javiera
authors.initials: J
authors.lastname: Torrejón
authors.affiliation: Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago, Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Escobar
authors.affiliation: Facultad de Medicina, Universidad de Chile, Santiago, Chile.|Departamento de Gastroenterología, Hospital Clínico de la Universidad de Chile, Santiago, Chile.
authors.forename: Caroll J
authors.initials: CJ
authors.lastname: Beltrán
mesh_terms: D000818:Animals; D001119:Arginase / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D003300:Copper / Q000737:chemistry / Q000276:immunology*; D051546:Cyclooxygenase 2 / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology*; D004789:Enzyme Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D009569:Nitric Oxide / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D009569:Nitric Oxide; D003300:Copper; D051546:Cyclooxygenase 2; D001119:Arginase; D015232:Dinoprostone; C000520:cuprous oxide
keywords: cyclooxygenase 2; immunotoxicology; inducible nitric oxide synthase; nanomedicine