PMID- 23380242
OWN - NLM
STAT- MEDLINE
DCOM- 20130913
LR  - 20240322
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 306
DP  - 2013 Apr 5
TI  - Titanium dioxide nanoparticles increase inflammatory responses in vascular 
      endothelial cells.
PG  - 1-8
LID - S0300-483X(13)00019-X [pii]
LID - 10.1016/j.tox.2013.01.014 [doi]
AB  - Atherosclerosis is a chronic inflammatory disease that remains the leading cause 
      of death in the United States. Numerous risk factors for endothelial cell 
      inflammation and the development of atherosclerosis have been identified, 
      including inhalation of ultrafine particles. Recently, engineered nanoparticles 
      (NPs) such as titanium (TiO2) NPs have attracted much attention due to their wide 
      range of applications. However, there are also great concerns surrounding 
      potential adverse health effects in vascular systems. Although TiO2 NPs are known 
      to induce oxidative stress and inflammation, the associated signaling pathways 
      have not been well studied. The focus of this work, therefore, deals with 
      examination of the cellular signaling pathways responsible for TiO2 NP-induced 
      endothelial oxidative stress and inflammation. In this study, primary vascular 
      endothelial cells were treated with TiO2 NPs for 2-16h at concentrations of 0-50 
      mug/mL. TiO2 NP exposure increased cellular oxidative stress and DNA binding of 
      NF-kappaB. Further, phosphorylation of Akt, ERK, JNK and p38 was increased in cells 
      exposed to TiO2 NPs. TiO2 NPs also significantly increased induction of mRNA and 
      protein levels of vascular cell adhesion molecule-1 (VCAM-1) and mRNA levels of 
      monocyte chemoattractant protein-1 (MCP-1). Pretreatment with inhibitors for 
      NF-kappaB (pyrrolidine dithiocarbamate), oxidative stress (epigallocatechin gallate 
      and apocynin), Akt (LY294002), ERK (PD98059), JNK (SP600125) and p38 (SB203580) 
      significantly attenuated TiO2 NP-induced MCP-1 and VCAM-1 gene expression. These 
      data indicate that TiO2 NPs can induce endothelial inflammatory responses via 
      redox-sensitive cellular signaling pathways.
CI  - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved.
FAU - Han, Sung Gu
AU  - Han SG
AD  - Superfund Research Program, University of Kentucky, Lexington, KY 40536, USA.
FAU - Newsome, Bradley
AU  - Newsome B
FAU - Hennig, Bernhard
AU  - Hennig B
LA  - eng
GR  - P42 ES007380/ES/NIEHS NIH HHS/United States
GR  - P42ES007380/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130201
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Chemokine CCL2)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0 (monocyte chemoattractant protein 1 (66-77))
RN  - 15FIX9V2JP (titanium dioxide)
RN  - D1JT611TNE (Titanium)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/genetics/metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Endothelial Cells/cytology/*drug effects/metabolism
MH  - Endothelium, Vascular/cytology/*drug effects/metabolism
MH  - Inflammation/*chemically induced
MH  - MAP Kinase Signaling System/drug effects
MH  - Microscopy, Electron, Scanning
MH  - Nanoparticles/*toxicity
MH  - Oxidative Stress/*drug effects
MH  - Peptide Fragments/genetics/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA, Messenger/chemistry/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Titanium/*toxicity
MH  - Vascular Cell Adhesion Molecule-1/genetics/metabolism
PMC - PMC3631470
MID - NIHMS441884
COIS- Conflict of interest statement The authors declare that there are no conflicts of 
      interest.
EDAT- 2013/02/06 06:00
MHDA- 2013/09/14 06:00
PMCR- 2014/04/05
CRDT- 2013/02/06 06:00
PHST- 2012/10/29 00:00 [received]
PHST- 2013/01/10 00:00 [revised]
PHST- 2013/01/22 00:00 [accepted]
PHST- 2013/02/06 06:00 [entrez]
PHST- 2013/02/06 06:00 [pubmed]
PHST- 2013/09/14 06:00 [medline]
PHST- 2014/04/05 00:00 [pmc-release]
AID - S0300-483X(13)00019-X [pii]
AID - 10.1016/j.tox.2013.01.014 [doi]
PST - ppublish
SO  - Toxicology. 2013 Apr 5;306:1-8. doi: 10.1016/j.tox.2013.01.014. Epub 2013 Feb 1.