Pulmonary Response to Surface-Coated Nanotitanium Dioxide Particles Includes Induction of Acute Phase Response Genes, Inflammatory Cascades, and Changes in MicroRNAs

A Toxicogenomic Study

Sabina Halappanavar, Petra Jackson, Andrew Williams, Keld A. Jensen, Ulla Vogel, Carole L. Yauk, Håkan Wallin

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Titanium dioxide nanoparticles (nanoTiO(2)) are used in various applications including in paints. NanoTiO(2) inhalation may induce pulmonary toxicity and systemic effects. However, the underlying molecular mechanisms are poorly understood. In this study, the effects of inhaled surface-coated nanoTiO(2) on pulmonary global messenger RNA (mRNA) and microRNA (miRNA) expression in mouse were characterized to provide insight into the molecular response. Female C57BL/6BomTac mice were exposed for 1 hr daily to 42.4 +/- 2.9 (SEM) mg surface-coated nanoTiO(2)/m(3) for 11 consecutive days by inhalation and were sacrificed 5 days following the last exposure. Physicochemical properties of the particles were determined. Pulmonary response to nanoTiO(2) was characterized using DNA microarrays and pathway-specific PCR arrays and related to data on pulmonary inflammation from bronchial lavages. NanoTiO(2) exposure resulted in increased levels of mRNA for acute phase markers serum amyloid A-1 (Saa1) and serum amyloid A-3 (Saa3), several C-X-C and C-C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more than 1.2-fold (adjusted P-value < 0.05) following exposure. Real time polymerase chain reaction confirmed the upregulation of miR-1, miR-449a and revealed dramatic induction of miR-135b (60-fold). Thus, inhalation of surface-coated nanoTiO(2) results in changes in the expression of genes associated with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research.
    OriginalsprogEngelsk
    TidsskriftEnvironmental and Molecular Mutagenesis
    Vol/bind52
    Udgave nummer6
    Sider (fra-til)425-439
    ISSN0893-6692
    DOI
    StatusUdgivet - 2011

    Citer dette

    Halappanavar, Sabina ; Jackson, Petra ; Williams, Andrew ; Jensen, Keld A. ; Vogel, Ulla ; Yauk, Carole L. ; Wallin, Håkan. / Pulmonary Response to Surface-Coated Nanotitanium Dioxide Particles Includes Induction of Acute Phase Response Genes, Inflammatory Cascades, and Changes in MicroRNAs : A Toxicogenomic Study . I: Environmental and Molecular Mutagenesis. 2011 ; Bind 52, Nr. 6. s. 425-439 .
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    title = "Pulmonary Response to Surface-Coated Nanotitanium Dioxide Particles Includes Induction of Acute Phase Response Genes, Inflammatory Cascades, and Changes in MicroRNAs: A Toxicogenomic Study",
    abstract = "Titanium dioxide nanoparticles (nanoTiO(2)) are used in various applications including in paints. NanoTiO(2) inhalation may induce pulmonary toxicity and systemic effects. However, the underlying molecular mechanisms are poorly understood. In this study, the effects of inhaled surface-coated nanoTiO(2) on pulmonary global messenger RNA (mRNA) and microRNA (miRNA) expression in mouse were characterized to provide insight into the molecular response. Female C57BL/6BomTac mice were exposed for 1 hr daily to 42.4 +/- 2.9 (SEM) mg surface-coated nanoTiO(2)/m(3) for 11 consecutive days by inhalation and were sacrificed 5 days following the last exposure. Physicochemical properties of the particles were determined. Pulmonary response to nanoTiO(2) was characterized using DNA microarrays and pathway-specific PCR arrays and related to data on pulmonary inflammation from bronchial lavages. NanoTiO(2) exposure resulted in increased levels of mRNA for acute phase markers serum amyloid A-1 (Saa1) and serum amyloid A-3 (Saa3), several C-X-C and C-C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more than 1.2-fold (adjusted P-value < 0.05) following exposure. Real time polymerase chain reaction confirmed the upregulation of miR-1, miR-449a and revealed dramatic induction of miR-135b (60-fold). Thus, inhalation of surface-coated nanoTiO(2) results in changes in the expression of genes associated with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research.",
    keywords = "microRNA, inflammation , nanotitanium dioxide, gene expression",
    author = "Sabina Halappanavar and Petra Jackson and Andrew Williams and Jensen, {Keld A.} and Ulla Vogel and Yauk, {Carole L.} and H{\aa}kan Wallin",
    year = "2011",
    doi = "10.1002/em.20639",
    language = "English",
    volume = "52",
    pages = "425--439",
    journal = "Environmental and Molecular Mutagenesis",
    issn = "0893-6692",
    publisher = "John/Wiley & Sons, Inc. John/Wiley & Sons Ltd.",
    number = "6",

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    Pulmonary Response to Surface-Coated Nanotitanium Dioxide Particles Includes Induction of Acute Phase Response Genes, Inflammatory Cascades, and Changes in MicroRNAs : A Toxicogenomic Study . / Halappanavar, Sabina; Jackson, Petra; Williams, Andrew; Jensen, Keld A.; Vogel, Ulla; Yauk, Carole L.; Wallin, Håkan.

    I: Environmental and Molecular Mutagenesis, Bind 52, Nr. 6, 2011, s. 425-439 .

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Pulmonary Response to Surface-Coated Nanotitanium Dioxide Particles Includes Induction of Acute Phase Response Genes, Inflammatory Cascades, and Changes in MicroRNAs

    T2 - A Toxicogenomic Study

    AU - Halappanavar, Sabina

    AU - Jackson, Petra

    AU - Williams, Andrew

    AU - Jensen, Keld A.

    AU - Vogel, Ulla

    AU - Yauk, Carole L.

    AU - Wallin, Håkan

    PY - 2011

    Y1 - 2011

    N2 - Titanium dioxide nanoparticles (nanoTiO(2)) are used in various applications including in paints. NanoTiO(2) inhalation may induce pulmonary toxicity and systemic effects. However, the underlying molecular mechanisms are poorly understood. In this study, the effects of inhaled surface-coated nanoTiO(2) on pulmonary global messenger RNA (mRNA) and microRNA (miRNA) expression in mouse were characterized to provide insight into the molecular response. Female C57BL/6BomTac mice were exposed for 1 hr daily to 42.4 +/- 2.9 (SEM) mg surface-coated nanoTiO(2)/m(3) for 11 consecutive days by inhalation and were sacrificed 5 days following the last exposure. Physicochemical properties of the particles were determined. Pulmonary response to nanoTiO(2) was characterized using DNA microarrays and pathway-specific PCR arrays and related to data on pulmonary inflammation from bronchial lavages. NanoTiO(2) exposure resulted in increased levels of mRNA for acute phase markers serum amyloid A-1 (Saa1) and serum amyloid A-3 (Saa3), several C-X-C and C-C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more than 1.2-fold (adjusted P-value < 0.05) following exposure. Real time polymerase chain reaction confirmed the upregulation of miR-1, miR-449a and revealed dramatic induction of miR-135b (60-fold). Thus, inhalation of surface-coated nanoTiO(2) results in changes in the expression of genes associated with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research.

    AB - Titanium dioxide nanoparticles (nanoTiO(2)) are used in various applications including in paints. NanoTiO(2) inhalation may induce pulmonary toxicity and systemic effects. However, the underlying molecular mechanisms are poorly understood. In this study, the effects of inhaled surface-coated nanoTiO(2) on pulmonary global messenger RNA (mRNA) and microRNA (miRNA) expression in mouse were characterized to provide insight into the molecular response. Female C57BL/6BomTac mice were exposed for 1 hr daily to 42.4 +/- 2.9 (SEM) mg surface-coated nanoTiO(2)/m(3) for 11 consecutive days by inhalation and were sacrificed 5 days following the last exposure. Physicochemical properties of the particles were determined. Pulmonary response to nanoTiO(2) was characterized using DNA microarrays and pathway-specific PCR arrays and related to data on pulmonary inflammation from bronchial lavages. NanoTiO(2) exposure resulted in increased levels of mRNA for acute phase markers serum amyloid A-1 (Saa1) and serum amyloid A-3 (Saa3), several C-X-C and C-C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more than 1.2-fold (adjusted P-value < 0.05) following exposure. Real time polymerase chain reaction confirmed the upregulation of miR-1, miR-449a and revealed dramatic induction of miR-135b (60-fold). Thus, inhalation of surface-coated nanoTiO(2) results in changes in the expression of genes associated with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research.

    KW - microRNA

    KW - inflammation

    KW - nanotitanium dioxide

    KW - gene expression

    U2 - 10.1002/em.20639

    DO - 10.1002/em.20639

    M3 - Journal article

    VL - 52

    SP - 425

    EP - 439

    JO - Environmental and Molecular Mutagenesis

    JF - Environmental and Molecular Mutagenesis

    SN - 0893-6692

    IS - 6

    ER -