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Pulmonary Effects of Engineered Nanoparticles

Pulmonary Effects of Engineered Nanoparticles. Hasan Bayram MD,PhD. Department of Respiratory Medicine, School of Medicine, University of Gaziantep E-mail: bayram@gantep . edu.tr. TTS 14 th Annual Congresss, Antalya 13-17 April 2011. Conflicts of Interest.

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Pulmonary Effects of Engineered Nanoparticles

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  1. Pulmonary Effects of Engineered Nanoparticles Hasan Bayram MD,PhD. Department of Respiratory Medicine, School of Medicine, University of Gaziantep E-mail: bayram@gantep.edu.tr TTS 14th Annual Congresss, Antalya 13-17 April 2011.

  2. Conflicts of Interest • Abdi Ibrahim Drug Company sponsored my attendance at international congresses twice in 2008 and 2010.

  3. PubMed Publications: “Nanoparticles” AND “Lung” AND “Toxicity” Publications

  4. Content • Nanoparticles entering the lung and the cell • Histopathological and inflammatory changes • Interaction with allergens and LPS • Effects of cell permeability and toxic parameters • Effects on cell viability, apoptosis, cell cycle (cell lines, primary cells, COPD cells) • Signaling pathways, transcriptional effects • Effects on oxidative stress • Summary

  5. Nanopartcle Application at Experimental Settings • Pharyngeal aspiration • Intra-tracheal instillation • Inhalation of aerosols • Exposure to freshly generated nanoparticles • Oral application • Intraarticular injection

  6. MWCNT in the Conducting Airways MWCNT MWCNT cilia Courtesy of John Howard, NIOSH 6

  7. MWCNT Distribution in Lung Tissue of Mice 1d After Inhalation of Aerosol (100mg/m3) for 6hrs MAKFJ PARK BRONCHİOL Ryman-Rasmussen JP et al. AJRCMB, 2009 .

  8. Migration of MWCNTs from Lung: Pleural Penetration Courtesy of John Howard, NIOSH 8

  9. Polystyrene Nanoparticle Trafficking Across Alveolar epithelium Yacobi NR et al, 2008

  10. Effects of Pharyngeal Aspiration of Single Wall Carbon Nanotube on Respiratory Tract in Mice 20 microns 20 microns Acute inflammation and fibrosis Granulomas 1 day post exposure 40 mg/mouse SWCNT 28 days post exposure 40 mg/mouse SWCNT Shvedova AA et al, 2005 10

  11. Percentage of Neutrophils in Lung Lavage of Rats and Mice 24 hr After Intratracheal Instillation Oberdörster G et al, 2005

  12. Effects of Titanium Dioxide Nanoparticles (TNP, 20/mg/kg) on Cytokine Levels in BAL After a Single Intratracheal Instillation Park EJ et al. Toxicology. 2009

  13. TiO2 Particles Coated with Silica Induce Level of BAL Cells of Mice Following 2h, 2h/4d, 2h/4wks Exposure A=2hrs B=2hrs/4dys C=2hrs/4wks • CXCL1 and TNF-α mRNA levels increased Rossi FM et al, Toxicol Sci. 2010

  14. Effects of Multi-walled Carbon Nanotubes (100nm; 0.4mg/ml)on Cytokine Release From Human Keratinocytes Witzmann FA et al, 2006

  15. Effect of 300µg/ml cnTiO2 on Expression of TNF-α and CXCL 1 mRNA in Human Macrophages after 3-24hrs Rossi FM et al, Toxicol Sci. 2010

  16. Effects of Inhaled TiO2 Particles (42mg/m3,11days) on microRNA Expression in Lungs of Mice Halappanavar S, et al. Environ Mol Mutagen. 2011

  17. Effects of Gold NPs ± LPS on Gene Expression of TNF-α, IL-8 and iNOS in a Triple-Culture Model of Macrophages, A549and Dentritic Cells • No effect on inflammatory and anti-inflammatory cytokine release, either. Brandenberger C, et al. Toxicol Appl Pharmacol, 2010.

  18. Effects of Titanium Dioxide Nanoparticles (TNP, 20/mg/kg) on Levels of IgE in BAL and Blood After a Single Intratracheal Instillation Park EJ et al. Toxicology. 2009

  19. IL-13 mRNA and Protein Levels at 1d After MWCNT Inhalation • Protein levels of PDGF and TGF-β1, • mRNA levels of IL-5, CCL2/MCP-1, CCL11/eotaxin • and CXCL9 were increased by OVA + MWCNT Ryman-Rasmussen JP et al. AJRCMB, 2009 .

  20. Lung Histopathology in Rats Exposed to MWCNT for 21d (blue indicatescollagen). MWCNT MWCNT + LPS Cesta MF et al. AJRCMB’09

  21. Effects of CB or MWCNT on Lung Injury Cesta MF et al. AJRCMB’09

  22. Tight Junction Expression and Transepithelial Electrical Resistance of A549 Cells • 10’=12µg/cm2 • 20’=19µg/cm2 • 30’=24µg/cm2 Rothen-Rutishauser B et al. Environ Sci Technol. 2009

  23. Effects of Zinc Oxide NPs on Electrical Resistance (RT) of Rat Alveolar Epithelial Cell Cultures Kim YH, et al. AJRCCM 2010.

  24. Effects of Zinc Oxide NPs on Lactate Dehydrogenase Release from Rat Alv. Epithelial Cell Cultures Kim YH, et al. AJRCCM 2010.

  25. Effects of Tungsten Carbide (WC) and Cobalt-doped Tungsten Carbide (WC-Co)NPson Viability ofMammalian Cells. A549 Alveolar-epithelial Cells Human Keratinocyte Cells Bastian S et al, 2009.

  26. Effects of TiO2 and MWCNT on BEAS-2B Cell Viability Gögebakan B, et al. TTS Congress, 2011.

  27. Effects of TiO2 on Viability of Bronchial Epithelial Cells from Smokers and COPD Patients Gögebakan B, et al. TTS Congress, 2011.

  28. Effects of MWCNT onViability of Bronchial Epithelial Cells from Smokers and COPD Patients Gögebakan B, et al. TTS Congress, 2011.

  29. Effects of 48h Incubation With TiO2 and MWCNT on BEAS-2B Cell Apoptosis MWCNT TiO2 Gögebakan B, et al. TTS Congress, 2011.

  30. Effects of Single-walled Carbon Nanotubes and C(60) Fullerenes on Cell Cycle of Mouse Lung Epithelial Cells Jacobsen NR et al, 2008

  31. Effects of 100µg/ml Polyamidoamine Dendrimer(PAMAM) Nanoparticles and 3-Methyladenine (Autophay Inhb.)on Autophagy in A549 Cells After 24hrs autophagosomes Li FT et al. J Mol Cell Biol. 2009

  32. Effects of Different Sized CeO2 Nanoparticles on pERK, p38 and pJNK in BEAS-2B Cells after 24 h Eom HJ et al. Toxicol Lett. 2009

  33. Expressions of NF-B, I-B and Nrf-2 in Cytosolic and Nuclear Fractions of BEAS-2B Cells Exposed to Different Sized CeO2Nanoparticles for 24h. Eom HJ et al. Toxicol Lett. 2009

  34. Effect of ZnO on Expression of IL-8 mRNA in Human BECs Wu W, et al. EHP, 2010

  35. Effect of ZnO Nanoparticles± NAC, on IntracellularCalcium Concentrations Huang CC et al. Toxicol In Vitro. 2009

  36. Effects of 20µg/cm2 Carbon Black and TiO2 NPs on Caspase 8 and Caspase 3/7 Activity in 16HBE14o- cells Hussain S, et al. Part Fibre Toxicol. 2010

  37. Non-cellular Nanoparticle ROS Activity Surface Area Particle Mass Elder A, et al 2008 (http://www.epa.gov)

  38. Effects of Cerium Oxide NPs (30nm) on ROS Induction in BEAS-2B Cells. Park EJ et al, 2008

  39. Summary • Nanoparticles enter into airways, parenchyme, cells • Causes collagen deposition, fibrosis, granuloma, inflammation • Modulate allergic response, synergism with LPS • Increases in epithelial permeability • Decreases in cell viability and cell cycle progression, increases in apoptosis and autophagy • Diseased cells (COPD) may be more susceptible • Activation of signaling mechanism and transcription factors that are sensitive to oxidative stress • ROS formation and induce oxidative stress

  40. Acknowledgements

  41. Thank You for Your Attentionbayram@gantep.edu.tr

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