Pulmonary Response to Surface-Coated Nanotitanium Dioxide Particles Includes Induction of Acute Phase Response Genes, Inflammatory Cascades, and Changes in MicroRNAs: A Toxicogenomic Study
Pulmonary Response to Surface-Coated Nanotitanium Dioxide Particles Includes Induction of Acute Phase Response Genes, Inflammatory Cascades, and Changes in MicroRNAs: A Toxicogenomic Study
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DOI：
10.1002/em.20639
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发表时间：
2011-07-01
影响因子：
2.8
通讯作者：
Wallin, Hakan
中科院分区：
文献类型：
--
作者：
Halappanavar, Sabina;Jackson, Petra;Wallin, Hakan
二氧化钛纳米颗粒(纳米二氧化钛(2))被用于各种应用，包括在涂料中。吸入纳米二氧化钛可引起肺部毒性和全身反应。然而，其潜在的分子机制却知之甚少。在这项研究中，吸入表面包覆的纳米二氧化钛对小鼠肺组织全局信使RNA(MRNA)和微RNA(MiRNA)表达的影响进行了表征，以期为深入了解其分子反应提供依据。雌性C57BL/6BomTac小鼠吸入42.4+/-2.9(扫描电子显微镜)镁表面包裹的纳米二氧化钛(2)/m(3)，每天1小时，连续11天，最后一次暴露后5天处死。测定了颗粒的物理化学性质。肺对纳米二氧化钛的反应通过DNA微阵列和路径特异性聚合酶链式反应阵列进行了表征，并与来自支气管灌洗液的肺部炎症数据相关联。纳米二氧化钛暴露导致急性时相标志物血清淀粉样蛋白A-1(Saa1)和血清淀粉样蛋白A-3(Saa3)、几种C-X-C和C-C基序趋化因子以及细胞因子肿瘤坏死因子基因的mRNA水平升高。Saa1和Saa3蛋白分析显示肺组织中Saa3有选择性上调。16个miRNAs在暴露后被超过1.2倍(调整后的P值和0.05)诱导。实时定量聚合酶链式反应证实miR-1、miR-449a表达上调，miR-135b表达显著增加(60倍)。因此，吸入表面包裹的纳米二氧化钛(2)会导致暴露5天后与急性期、炎症和免疫反应相关的基因表达的变化，同时伴随着几个miRNAs的变化。这些miRNAs在肺部对吸入颗粒物的反应中的作用尚不清楚，值得进一步研究。环境。摩尔。诱变剂。2011年，52：425-439。(C)2011年Wiley-Liss，Inc.(Dagger)
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. Environ. Mol. Mutagen. 52:425-439, 2011. (C) 2011 Wiley-Liss, Inc.(dagger)