Titanium dioxide nanoparticles increase inflammatory responses in vascular endothelial cells

Abstract

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 2–16 h at concentrations of 0–50 µg/mL. TiO2 NP exposure increased cellular oxidative stress and DNA binding of NF-κB. 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-κB (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, as well as activation of NF-κB. These data indicate that TiO2 NPs can induce endothelial inflammatory responses via redox-sensitive cellular signaling pathways.

Effect of inhibitors of endocytosis and NF-kB signal pathway on folate-conjugated nanoparticle endocytosis by rat Kupffer cells

“…At the same time, a NF-kB signal pathway inhibitor, PDTC (Sigma-Aldrich) was added at 10 µM/mL to inhibit the inflammatory effect, 29 thus inhibiting the endocytosis of FPA/EPI NPs. Following preincubation for 24 h at 37°C, the inhibitor solutions were removed, and freshly prepared FPA/EPI NPs, in medium containing inhibitors at the same concentrations, were added and further incubated for another 2 h. Subsequently, the cells were washed as described previously.…”

(Q)SAR modelling of nanomaterial toxicity: A critical review

“…It has been demonstrated in literature that carbon nanotubes (CNTs) are capable of inducing reactive oxygen species (ROS) (C. S. Sharma, et al, 2007) and pulmonary effects (Shvedova, et al, 2005). It has also been shown in toxicological studies that nano-sized titanium dioxide (TiO2) particles have the potential to induce cytotoxic (Saquib, et al, 2012;Setyawati, et al, 2012), genotoxic (Shukla, et al, 2011;Trouiller, Reliene, Westbrook, Solaimani, & Schiestl, 2009) and inflammatory effects (Grassian, O'Shaughnessy, Adamcakova-Dodd, Pettibone, & Thorne, 2007;S. G. Han, Newsome, & Hennig, 2013).…”

Protective effects of EGCG through Inhibition of NADPH oxidase expression in endothelial cells

“…Oxidative stress, as a result of increased production of ROS (e.g., superoxide anion), is a critical event in endothelial inflammation. A redox-sensitive transcription factor, NF-κB, has been shown to up-regulate endothelial inflammatory genes, including VCAM-1 and MCP-1 (10). Thus, our data suggest that EGCG can down-regulate the mRNA expression of NADPH oxidase subunits, specifically p22phox and Nox2, which may result in reduced superoxide anion production.…”

“…Cell culture and experimental conditions Primary vascular endothelial cells were isolated from porcine pulmonary arteries and cultured as previously described (10). Stock solutions of EGCG (Cayman Chemicals, Ann Arbor, MI, USA) were prepared in DMSO.…”

“…Reverse transcription was performed using the AMV reverse transcription system (Promega, Madison, WI, USA). mRNA expression levels were assessed by quantitative real-time PCR (7300 Real-Time PCR System; Applied Biosystems, Foster City, CA, USA) and SYBR Green master mix (Applied Biosystems) as described previously (10,11). Sequences for mRNAs were designed using Primer Express Software 3.0 for real-time PCR (Applied Biosystems) and synthesized by Integrated DNA Technologies, Inc. (Coralville, IA, USA).…”