title: Nrf2 protects the lung against inflammation induced by titanium dioxide nanoparticles: A positive regulator role of Nrf2 on cytokine release.
abstract: Titanium dioxide nanoparticles (TiO2 NPs) have been classified as possibly carcinogenic to humans and they are an important nanomaterial widely used in pharmaceutical and paint industries. Inhalation is one of the most important routes of exposure in occupational settings. Several experimental models have shown that oxidative stress and inflammation are key mediators of cell damage. In this regard, Nrf2 modulates cytoprotection against oxidative stress and inflammation, however, its role in inflammation induced by TiO2 NPs exposure has been less investigated. The aim of this work was to investigate the role of Nrf2 in the cytokines produced after 4 weeks of TiO2 NPs exposure (5 mg/kg/2 days/week) using wild-type and Nrf2 knockout C57bl6 mice. Results showed that Nrf2 protects against inflammation and oxidative damage induced by TiO2 NPs exposure, however, Nrf2 is a positive mediator in the expression of IFN-γ, TNF-α, and TGF-β in bronchial epithelium and alveolar space after 4 weeks of exposure. These results suggest that Nrf2 has a central role in up-regulation of cytokines released during inflammation induced by TiO2 NPs and those cytokines are needed to cope with histological alterations in lung tissue.
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, UNAM, Estado de México, 54059, México.
authors.forename: Norma L
authors.initials: NL
authors.lastname: Delgado-Buenrostro
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, UNAM, Estado de México, 54059, México.
authors.forename: Estefany I
authors.initials: EI
authors.lastname: Medina-Reyes
authors.affiliation: Departamento de Bioquímica e Instituto de Investigaciones Biomédicas "Alberto Sols" Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, España.
authors.forename: Isabel
authors.initials: I
authors.lastname: Lastres-Becker
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, UNAM, Estado de México, 54059, México.|Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Distrito Federal, CP, 11340, México.
authors.forename: Verónica
authors.initials: V
authors.lastname: Freyre-Fonseca
authors.affiliation: California NanoSystems Institute, University of California, Los Angeles, California, 90095.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Department of Pathology, Experimental Pathology Section, National Institute of Medical Science and Nutrition, Salvador Zubiran, Mexico City, Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
authors.affiliation: Department of Pathology, Experimental Pathology Section, National Institute of Medical Science and Nutrition, Salvador Zubiran, Mexico City, Mexico.
authors.forename: Brenda
authors.initials: B
authors.lastname: Marquina
authors.affiliation: Departamento de Biología, Facultad de Química, Laboratorio 209, Edificio F, UNAM, Distrito Federal, 04510, México.
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.affiliation: Departamento de Bioquímica e Instituto de Investigaciones Biomédicas "Alberto Sols" Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, España.
authors.forename: Sandra
authors.initials: S
authors.lastname: Espada
authors.affiliation: Departamento de Bioquímica e Instituto de Investigaciones Biomédicas "Alberto Sols" Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, España.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuadrado
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, UNAM, Estado de México, 54059, México.
authors.forename: Yolanda I
authors.initials: YI
authors.lastname: Chirino
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000209:etiology*; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D014025:Titanium / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C009495:titanium dioxide; D007371:Interferon-gamma; D014025:Titanium; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Nrf2; lung inflammation; titanium dioxide nanoparticles