Titanium dioxide nanoparticles increase inflammatory responses in vascular endothelial cells

Area of Science:

• Biomedical Science
• Toxicology
• Nanotechnology

Background:

• Atherosclerosis is a leading cause of death, with endothelial inflammation a key factor.
• Ultrafine particles and engineered nanoparticles, like titanium dioxide (TiO2) NPs, are emerging environmental and industrial concerns for vascular health.
• The specific cellular signaling pathways mediating TiO2 NP-induced endothelial inflammation remain incompletely understood.

Purpose of the Study:

• To investigate the cellular signaling pathways involved in titanium dioxide nanoparticle (TiO2 NP)-induced oxidative stress and inflammation in primary vascular endothelial cells.
• To elucidate the role of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in TiO2 NP toxicity.

Main Methods:

• Primary vascular endothelial cells were exposed to varying concentrations of TiO2 NPs for defined periods.
• Assessed cellular oxidative stress markers, NF-κB DNA binding activity, and phosphorylation of key signaling proteins (Akt, ERK, JNK, p38).
• Quantified mRNA and protein expression of inflammatory markers, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1).
• Utilized specific inhibitors for NF-κB, oxidative stress, and signaling pathways to determine their role in TiO2 NP effects.

Main Results:

• TiO2 NP exposure significantly increased cellular oxidative stress and NF-κB activation.
• Phosphorylation of Akt, ERK, JNK, and p38 signaling proteins was elevated following TiO2 NP treatment.
• TiO2 NPs markedly upregulated VCAM-1 and MCP-1 gene and protein expression.
• Inhibitor pretreatment significantly attenuated TiO2 NP-induced MCP-1 and VCAM-1 expression, confirming pathway involvement.

Conclusions:

• Titanium dioxide nanoparticles induce significant oxidative stress and inflammatory responses in vascular endothelial cells.
• These effects are mediated through the activation of redox-sensitive cellular signaling pathways, including NF-κB, Akt, ERK, JNK, and p38.
• Understanding these pathways is crucial for assessing the vascular risks associated with TiO2 NP exposure.