title: Nano-TiO₂ particles impair adhesion of airway epithelial cells to fibronectin.
abstract: Titanium dioxide engineered nanoparticles (nano-TiO(2)) are widely used in the manufacturing of a number of products. Due to their size (<100 nm), when inhaled they may be deposited in the distal lung regions and damage Clara cells. We investigated the mechanisms by which short-term (1-h) incubation of human airway Clara-like (H441) cells to nano-TiO(2) (6 nm in diameter) alters the ability of H441 cells to adhere to extracellular matrix. Our results show that 1h post-incubation, there was a 3-fold increase of extracellular H(2)O(2), increased intracellular oxidative stress as demonstrated by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) oxidation, and a 5-fold increase of phosphor-ERK1/2 as measured by Western blotting. These changes were accompanied by a 25% decrease of H441 adherence to fibronectin (p<0.05 compared to vehicle incubated H441 cells). Pretreatment with the ERK1/2 inhibitor U0126 for 3h, partially prevented this effect. In conclusion, short-term exposure of H441 cells to nano-TiO(2) appears to reduce adherence to fibronectin due to oxidative stress and activation of ERK1/2.
authors.affiliation: Department of Anesthesiology, University of Alabama at Birmingham, 35294 Birmingham, AL, USA. szarog@med.uth.gr
authors.forename: Sotirios G
authors.initials: SG
authors.lastname: Zarogiannis
authors.forename: Aristotelis S
authors.initials: AS
authors.lastname: Filippidis
authors.forename: Solana
authors.initials: S
authors.lastname: Fernandez
authors.forename: Asta
authors.initials: A
authors.lastname: Jurkuvenaite
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Ambalavanan
authors.forename: Andrei
authors.initials: A
authors.lastname: Stanishevsky
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Vohra
authors.forename: Sadis
authors.initials: S
authors.lastname: Matalon
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000704:Analysis of Variance; D002448:Cell Adhesion / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D053768:Metal Nanoparticles / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013997:Time Factors; D014025:Titanium / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D014157:Transcription Factors; C478359:WDR77 protein, human; C009495:titanium dioxide; D006861:Hydrogen Peroxide; D014025:Titanium; D019950:Mitogen-Activated Protein Kinase 1