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. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 98

1. 1.

   2006.

   Not in our library

2. 2.

   Alvo M, Liu Z, Williams A, Yauk C. Testing for mean and correlation changes in microarray experiments: An application for pathway analysis. BMC Bioinformatics. 2010;11:60.

   Not in our library10.1186/1471-2105-11-60

3. 3.

   Andre E, Stoeger T, Takenaka S, Bahnweg M, Ritter B, Karg E, Lentner B, Reinhard C, Schulz H, Wjst M. Inhalation of ultrafine carbon particles triggers biphasic pro-inflammatory response in the mouse lung. Eur Respir J. 2006;28:275-285.

   Not in our library10.1183/09031936.06.00071205

4. 4.

   Baggs RB, Ferin J, Oberdorster G. Regression of pulmonary lesions produced by inhaled titanium dioxide in rats. Vet Pathol. 1997;34:592-597.

   Not in our library10.1177/030098589703400607

5. 5.

   Bermudez E, Mangum JB, Asgharian B, Wong BA, Reverdy EE, Janszen DB, Hext PM, Warheit DB, Everitt JI. Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles. Toxicol Sci. 2002;70:86-97.

   Not in our library10.1093/toxsci/70.1.86

6. 6.

   Bermudez E, Mangum JB, Wong BA, Asgharian B, Hext PM, Warheit DB, Everitt JI. Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles. Toxicol Sci. 2004;77:347-357.

   Not in our library10.1093/toxsci/kfh019

7. 7.

   Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, Loda M, Weber G, Mark EJ, Lander ES, Wong W, Johnson BE, Golub TR, Sugarbaker DJ, Meyerson M. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA. 2001;98:13790-13795.

   Not in our library10.1073/pnas.191502998

8. 8.

   Bhattacharya K, Cramer H, Albrecht C, Schins R, Rahman Q, Zimmermann U, Dopp E. Vanadium pentoxide-coated ultrafine titanium dioxide particles induce cellular damage and micronucleus formation in V79 cells. J Toxicol Environ Health A. 2008;71:976-980.

   Not in our library10.1080/15287390801989218

9. 9.

   Bolstad BM, Irizarry RA, Astrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003;19:185-193.

   Not in our library10.1093/bioinformatics/19.2.185

10. 10.
    The potential risks of nanomaterials: a review carried out for ECETOC. · 2006

    No notice
11. 11.

    Bueno MJ, de Castro IP, Malumbres M. Control of cell proliferation pathways by microRNAs. Cell Cycle. 2008;7:3143-3148.

    Not in our library10.4161/cc.7.20.6833

12. 12.

    Carleton M, Cleary MA, Linsley PS. MicroRNAs and cell cycle regulation. Cell Cycle. 2007;6:2127-2132.

    Not in our library10.4161/cc.6.17.4641

13. 13.

    Chen HW, Su SF, Chien CT, Lin WH, Yu SL, Chou CC, Chen JJ, Yang PC. Titanium dioxide nanoparticles induce emphysema-like lung injury in mice. FASEB J. 2006;20:2393-2395.

    Not in our library10.1096/fj.06-6485fje

14. 14.

    Chen J, Dong X, Zhao J, Tang G. In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection. J Appl Toxicol. 2009;29:330-337.

    Not in our library10.1002/jat.1414

15. 15.

    Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10:704-714.

    Not in our library10.1038/nrg2634

16. 16.

    Cui X, Hwang JT, Qiu J, Blades NJ, Churchill GA. Improved statistical tests for differential gene expression by shrinking variance components estimates. Biostatistics. 2005;6:59-75.

    Not in our library10.1093/biostatistics/kxh018

17. 17.

    Cullen RT, Tran CL, Buchanan D, Davis JM, Searl A, Jones AD, Donaldson K. Inhalation of poorly soluble particles. I. Differences in inflammatory response and clearance during exposure. Inhal Toxicol. 2000;12:1089-1111.

    Not in our library10.1080/08958370050166787

18. 18.

    Dankovic D, Kuempel E, Wheeler M. An approach to risk assessment for TiO2. Inhal Toxicol. 2007;19(Suppl 1):205-212.

    Not in our library10.1080/08958370701497754

19. 19.

    de Haar C, Hassing I, Bol M, Bleumink R, Pieters R. Ultrafine but not fine particulate matter causes airway inflammation and allergic airway sensitization to co-administered antigen in mice. Clin Exp Allergy. 2006;36:1469-1479.

    Not in our library10.1111/j.1365-2222.2006.02586.x

20. 20.

    Driscoll KE, Hassenbein DG, Carter J, Poynter J, Asquith TN, Grant RA, Whitten J, Purdon MP, Takigiku R. Macrophage inflammatory proteins 1 and 2: Expression by rat alveolar macrophages, fibroblasts, and epithelial cells and in rat lung after mineral dust exposure. Am J Respir Cell Mol Biol. 1993;8:311-318.

    Not in our library10.1165/ajrcmb/8.3.311

21. 21.

    Drumm K, Schindler H, Buhl R, Kustner E, Smolarski R, Kienast K. Indoor air pollutants stimulate interleukin-8-specific mRNA expression and protein secretion of alveolar macrophages. Lung. 1999;177:9-19.

    Not in our library10.1007/pl00007628

22. 22.

    Farraj AK, Hazari MS, Haykal-Coates N, Lamb C, Winsett DW, Ge Y, Ledbetter AD, Carll AP, Bruno M, Ghio A, Costa DL. ST depression, arrhythmia, vagal dominance, and reduced cardiac microRNA in particulate-exposed rats. Am J Respir Cell Mol Biol. 2010.

    Not in our library10.1165/rcmb.2009-0456oc

23. 23.

    Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature. 2004;432:917-921.

    Not in our library10.1038/nature03104

24. 24.

    Ganapathi MK, May LT, Schultz D, Brabenec A, Weinstein J, Sehgal PB, Kushner I. Role of interleukin-6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines. Biochem Biophys Res Commun. 1988;157:271-277.

    Not in our library10.1016/s0006-291x(88)80043-3

25. 25.

    Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annu Rev Med. 2009;60:167-179.

    Not in our library10.1146/annurev.med.59.053006.104707

26. 26.

    Golpon HA, Coldren CD, Zamora MR, Cosgrove GP, Moore MD, Tuder RM, Geraci MW, Voelkel NF. Emphysema lung tissue gene expression profiling. Am J Respir Cell Mol Biol. 2004;31:595-600.

    Not in our library10.1165/rcmb.2004-0008oc

27. 27.

    Granville CA, Dennis PA. An overview of lung cancer genomics and proteomics. Am J Respir Cell Mol Biol. 2005;32:169-176.

    Not in our library10.1165/rcmb.f290

28. 28.

    Guil S, Esteller M. DNA methylomes, histone codes and miRNAs: Tying it all together. Int J Biochem Cell Biol. 2009;41:87-95.

    Not in our library10.1016/j.biocel.2008.09.005

29. 29.

    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57-70.

    Not in our library10.1016/s0092-8674(00)81683-9

30. 30.

    Heinrich U, Fuhst R, Rittinghausen S, Creutzenberg O, Bellmann B, Koch W, Levesen K. Chronic inhalation exposure of wistar rats and two different strains of mice to diesel engine exhaust, carbon black, and titanium dioxide. Inhal Toxicol. 1995;7:533-556.

    Not in our library

31. 31.

    Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H, Maru Y. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol. 2008;10:1349-1355.

    Not in our library10.1038/ncb1794

32. 32.

    Benjamini Y, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc Ser B Stat Methodol. 1995;57:289-300.

    Not in our library

33. 33.
    Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice · 2010

    No notice
34. 34.

    Hougaard KS, Jensen KA, Nordly P, Taxvig C, Vogel U, Saber AT, Wallin H. Effects of prenatal exposure to diesel exhaust particles on postnatal development, behavior, genotoxicity and inflammation in mice. Part Fibre Toxicol. 2008;5:3.

    Not in our library10.1186/1743-8977-5-3

35. 35.

    Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44-57.

    Not in our library10.1038/nprot.2008.211

36. 36.

    Hudder A, Novak RF. miRNAs: Effectors of environmental influences on gene expression and disease. Toxicol Sci. 2008;103:228-240.

    Not in our library10.1093/toxsci/kfn033

37. 37.
    Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice · 2009

    No notice
38. 38.
    Disruption of MicroRNA Expression in Human Airway Cells by Diesel Exhaust Particles Is Linked to Tumorigenesis-Associated Pathways · 2009

    No notice
39. 39.

    Jensen LE, Whitehead AS. Regulation of serum amyloid A protein expression during the acute-phase response. Biochem J. 1998;334(Part 3):489-503.

    Not in our library10.1042/bj3340489

40. 40.

    Jeyaseelan S, Manzer R, Young SK, Yamamoto M, Akira S, Mason RJ, Worthen GS. Induction of CXCL5 during inflammation in the rodent lung involves activation of alveolar epithelium. Am J Respir Cell Mol Biol. 2005;32:531-539.

    Not in our library10.1165/rcmb.2005-0063oc

41. 41.

    Jiang SL, Lozanski G, Samols D, Kushner I. Induction of human serum amyloid A in Hep 3B cells by IL-6 and IL-1 beta involves both transcriptional and post-transcriptional mechanisms. J Immunol. 1995;154:825-831.

    Not in our library

42. 42.
    Differentiation of two types of mobilized peripheral blood stem cells by microRNA and cDNA expression analysis · 2008

    Not checked
43. 43.

    Kerr MK. Design considerations for efficient and effective microarray studies. Biometrics. 2003;59:822-828.

    Not in our library10.1111/j.0006-341x.2003.00096.x

44. 44.

    Kerr MK, Churchill GA. Bootstrapping cluster analysis: Assessing the reliability of conclusions from microarray experiments. Proc Natl Acad Sci USA. 2001;98:8961-8965.

    Not in our library10.1073/pnas.161273698

45. 45.

    Kerr MK, Churchill GA. Statistical design and the analysis of gene expression microarray data. Genet Res. 2007;89:509-514.

    Not in our library10.1017/s0016672308009713

46. 46.

    Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009;10:126-139.

    Not in our library10.1038/nrm2632

47. 47.

    Kong W, Zhao JJ, He L, Cheng JQ. Strategies for profiling microRNA expression. J Cell Physiol. 2009;218:22-25.

    Not in our library10.1002/jcp.21577

48. 48.

    Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foa R, Schliwka J, Fuchs U, Novosel A, Muller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, hoksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129:1401-1414.

    Not in our library10.1016/j.cell.2007.04.040

49. 49.

    Lee KP, Trochimowicz HJ, Reinhardt CF. Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years. Toxicol Appl Pharmacol. 1985;79:179-192.

    Not in our library10.1016/0041-008x(85)90339-4

50. 50.

    Lema C, Cunningham MJ. MicroRNAs and their implications in toxicological research. Toxicol Lett. 2010;198:100-105.

    Not in our library10.1016/j.toxlet.2010.06.019

51. 51.

    Lowell CA, Stearman RS, Morrow JF. Transcriptional regulation of serum amyloid A gene expression. J Biol Chem. 1986;261:8453-8461.

    Not in our library

52. 52.

    Lu TX, Munitz A, Rothenberg ME. MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol. 2009;182:4994-5002.

    Not in our library10.4049/jimmunol.0803560

53. 53.

    Lynam-Lennon N, Maher SG, Reynolds JV. The roles of microRNA in cancer and apoptosis. Biol Rev Camb Philos Soc. 2009;84:55-71.

    Not in our library10.1111/j.1469-185x.2008.00061.x

54. 54.

    Ma-Hock L, Burkhardt S, Strauss V, Gamer AO, Wiench K, van Ravenzwaay B, Landsiedel R. Development of a short-term inhalation test in the rat using nano-titanium dioxide as a model substance. Inhal Toxicol. 2009;21:102-118.

    Not in our library10.1080/08958370802361057

55. 55.

    Meek RL, Benditt EP. Amyloid A gene family expression in different mouse tissues. J Exp Med. 1986;164:2006-2017.

    Not in our library10.1084/jem.164.6.2006

56. 56.

    Mei N, Fuscoe JC, Lobenhofer EK, Guo L. Application of microarray-based analysis of gene expression in the field of toxicogenomics. Methods Mol Biol. 2010;597:227-241.

    Not in our library10.1007/978-1-60327-389-3_16

57. 57.

    Morrow JF, Stearman RS, Peltzman CG, Potter DA. Induction of hepatic synthesis of serum amyloid A protein and actin. Proc Natl Acad Sci USA. 1981;78:4718-4722.

    Not in our library10.1073/pnas.78.8.4718

58. 58.

    Nakao I, Kanaji S, Ohta S, Matsushita H, Arima K, Yuyama N, Yamaya M, Nakayama K, Kubo H, Watanabe M, Sagara H, Sugiyama K, Tanaka H, Toda S, Hayashi H, Inoue H, Hoshino T, Shiraki A, Inoue M, Suzuki K, Aizawa H, Okinami S, Nagai H, Hasegawa M, Fukuda T, Green ED, Izuhara K. Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease. J Immunol. 2008;180:6262-6269.

    Not in our library10.4049/jimmunol.180.9.6262

59. 59.

    Ning W, Li CJ, Kaminski N, Feghali-Bostwick CA, Alber SM, Di YP, Otterbein SL, Song R, Hayashi S, Zhou Z, Pinsky DJ, Watkins SC, Pilewski JM, Sciurba FC, Peters DG, Hogg JC, Choi AM. Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease. Proc Natl Acad Sci USA. 2004;101:14895-14900.

    Not in our library10.1073/pnas.0401168101

60. 60.

    Nitto T, Inoue T, Node K. Alternative spliced variants in the pantetheinase family of genes expressed in human neutrophils. Gene. 2008;426:57-64.

    Not in our library10.1016/j.gene.2008.08.019

61. 61.

    Noonan EJ, Place RF, Pookot D, Basak S, Whitson JM, Hirata H, Giardina C, Dahiya R. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene. 2009;28:1714-1724.

    Not in our library10.1038/onc.2009.19

62. 62.

    Oberdorster G. Lung particle overload: Implications for occupational exposures to particles. Regul Toxicol Pharmacol. 1995;21:123-135.

    Not in our library10.1006/rtph.1995.1017

63. 63.
    Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy · 2005

    No notice
64. 64.
    Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles · 2005

    No notice
65. 65.

    Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C. Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol. 2004;16:437-445.

    Not in our library10.1080/08958370490439597

66. 66.

    Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A, Kreyling W, Cox C. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A. 2002;65:1531-1543.

    Not in our library10.1080/00984100290071658

67. 67.

    Park EJ, Kim H, Kim Y, Yi J, Choi K, Park K. Inflammatory responses may be induced by a single intratracheal instillation of iron nanoparticles in mice. Toxicology. 2010;275:65-71.

    Not in our library10.1016/j.tox.2010.06.002

68. 68.

    Park EJ, Yoon J, Choi K, Yi J, Park K. Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation. Toxicology. 2009;260:37-46.

    Not in our library10.1016/j.tox.2009.03.005

69. 69.

    Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30:e36.

    Not in our library10.1093/nar/30.9.e36

70. 70.

    Ploner A. Heatplus: A heat map displaying covariates and coloring clusters. R package Version 1.14.0. 2008.

    Not in our library

71. 71.
    Ambient particulate air pollution, heart rate variability, and blood markers of inflammation in a panel of elderly subjects. · 2004

    No notice
72. 72.

    Pott F, Althoff G-H, Roller M, Hohr D, Friemann J, Mohr U, Dungworth DL. High acute toxicity of hydrophobic ultrafine titanium dioxide in an intratracheal study with several dusts in rats. ILSI Monographs Relationship Between Respiratory Disease and Exposure to Air Pollution. 1998;270-277.

    Not in our library

73. 73.

    R: A Language and Environment for Statistical Computing. TRDC. 2004.

    Not in our library

74. 74.

    R: A Language and Environment for Statistical Computing. 2009.

    Not in our library

75. 75.
    Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. · 2002

    No notice
76. 76.

    Rehn B, Seiler F, Rehn S, Bruch J, Maier M. Investigations on the inflammatory and genotoxic lung effects of two types of titanium dioxide: Untreated and surface treated. Toxicol Appl Pharmacol. 2003;189:84-95.

    Not in our library10.1016/s0041-008x(03)00092-9

77. 77.

    Renwick LC, Brown D, Clouter A, Donaldson K. Increased inflammation and altered macrophage chemotactic responses caused by two ultrafine particle types. Occup Environ Med. 2004;61:442-447.

    Not in our library10.1136/oem.2003.008227

78. 78.

    Rossi EM, Pylkkanen L, Koivisto AJ, Vippola M, Jensen KA, Miettinen M, Sirola K, Nykasenoja H, Karisola P, Stjernvall T, Vanhala E, Kiilunen M, Pasanen P, Makinen M, Hameri K, Joutsensaari J, Tuomi T, Jokiniemi J, Wolff H, Savolainen K, Matikainen S, Alenius H. Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice. Toxicol Sci. 2010;113:422-433.

    Not in our library10.1093/toxsci/kfp254

79. 79.

    Ruckerl R, Ibald-Mulli A, Koenig W, Schneider A, Woelke G, Cyrys J, Heinrich J, Marder V, Frampton M, Wichmann HE, Peters A. Air pollution and markers of inflammation and coagulation in patients with coronary heart disease. Am J Respir Crit Care Med. 2006;173:432-441.

    Not in our library10.1164/rccm.200507-1123oc

80. 80.

    Saber AT, Halappanavar S, Folkmann JK, Bornholdt J, Boisen AM, Moller P, Williams A, Yauk C, Vogel U, Loft S, Wallin H. Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation. Part Fibre Toxicol. 2009;6:12.

    Not in our library10.1186/1743-8977-6-12

81. 81.
    Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states · 2009

    No notice
82. 82.

    Sayes CM, Wahi R, Kurian PA, Liu Y, West JL, Ausman KD, Warheit DB, Colvin VL. Correlating nanoscale titania structure with toxicity: A cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci. 2006;92:174-185.

    Not in our library10.1093/toxsci/kfj197

83. 83.

    Schneeman TA, Bruno ME, Schjerven H, Johansen FE, Chady L, Kaetzel CS. Regulation of the polymeric Ig receptor by signaling through TLRs 3 and 4: Linking innate and adaptive immune responses. J Immunol. 2005;175:376-384.

    Not in our library10.4049/jimmunol.175.1.376

84. 84.

    Spira A, Beane J, Pinto-Plata V, Kadar A, Liu G, Shah V, Celli B, Brody JS. Gene expression profiling of human lung tissue from smokers with severe emphysema. Am J Respir Cell Mol Biol. 2004;31:601-610.

    Not in our library10.1165/rcmb.2004-0273oc

85. 85.

    Sun BK, Tsao H. Small RNAs in development and disease. J Am Acad Dermatol. 2008;59:725-737.

    Not in our library10.1016/j.jaad.2008.08.017

86. 86.

    Takaya T, Ono K, Kawamura T, Takanabe R, Kaichi S, Morimoto T, Wada H, Kita T, Shimatsu A, Hasegawa K. MicroRNA-1 and microRNA-133 in spontaneous myocardial differentiation of mouse embryonic stem cells. Circ J. 2009;73:1492-1497.

    Not in our library10.1253/circj.cj-08-1032

87. 87.

    Taylor EL, Gant TW. Emerging fundamental roles for non-coding RNA species in toxicology. Toxicology. 2008;246:34-39.

    Not in our library10.1016/j.tox.2007.12.030

88. 88.

    Tran CL, Buchanan D, Cullen RT, Searl A, Jones AD, Donaldson K. Inhalation of poorly soluble particles. II. Influence of particle surface area on inflammation and clearance. Inhal Toxicol. 2000;12:1113-1126.

    Not in our library10.1080/08958370050166796

89. 89.
    microRNAs and the immune response · 2009

    No notice
90. 90.

    van Ravenzwaay B, Landsiedel R, Fabian E, Burkhardt S, Strauss V, Ma-Hock L. Comparing fate and effects of three particles of different surface properties: Nano-TiO(2), pigmentary TiO(2) and quartz. Toxicol Lett. 2009;186:152-159.

    Not in our library10.1016/j.toxlet.2008.11.020

91. 91.

    Wang JJ, Sanderson BJ, Wang H. Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells. Mutat Res. 2007;628:99-106.

    Not in our library10.1016/j.mrgentox.2006.12.003

92. 92.

    Wang Y, Liang Y, Lu Q. MicroRNA epigenetic alterations: Predicting biomarkers and therapeutic targets in human diseases. Clin Genet. 2008;74:307-315.

    Not in our library10.1111/j.1399-0004.2008.01075.x

93. 93.

    Warheit DB, Brock WJ, Lee KP, Webb TR, Reed KL. Comparative pulmonary toxicity inhalation and instillation studies with different TiO2 particle formulations: Impact of surface treatments on particle toxicity. Toxicol Sci. 2005;88:514-524.

    Not in our library10.1093/toxsci/kfi331

94. 94.

    Warheit DB, Frame SR. Characterization and reclassification of titanium dioxide-related pulmonary lesions. J Occup Environ Med. 2006;48:1308-1313.

    Not in our library10.1097/01.jom.0000215385.71548.b0

95. 95.

    Warheit DB, Hansen JF, Yuen IS, Kelly DP, Snajdr SI, Hartsky MA. Inhalation of high concentrations of low toxicity dusts in rats results in impaired pulmonary clearance mechanisms and persistent inflammation. Toxicol Appl Pharmacol. 1997;145:10-22.

    Not in our library10.1006/taap.1997.8102

96. 96.

    Warheit DB, Webb TR, Sayes CM, Colvin VL, Reed KL. Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: Toxicity is not dependent upon particle size and surface area. Toxicol Sci. 2006;91:227-236.

    Not in our library10.1093/toxsci/kfj140

97. 97.

    Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: MicroRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11:228-234.

    Not in our library10.1038/ncb0309-228

98. 98.

    Wu H, Kerr M, Cui X, Churchill G. Maanova: A Software Package for the Analysis of Spotted cDNA Microarray Experiments. 2003;313-341.

    Not in our library

Cited by papers we hold 5

• Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale · 2020
  No notice
• Inhaled Pollutants: The Molecular Scene behind Respiratory and Systemic Diseases Associated with Ultrafine Particulate Matter · 2017
  No notice
• Transcriptomic analysis reveals novel mechanistic insight into murine biological responses to multi-walled carbon nanotubes in lungs and cultured lung epithelial cells. · 2013
  Not checked
• Titanium dioxide nanoparticles: a review of current toxicological data · 2013
  No notice
• Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver · 2012
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.