1 research outputs found
Cytotoxic and Proinflammatory Effects of Metal-Based Nanoparticles on THP‑1 Monocytes Characterized by Combined Proteomics Approaches
Thorough
characterization of toxic effects of nanoparticles (NP)
is desirable due to the increasing risk of potential environmental
contamination by NP. In the current study, we combined three recently
developed proteomics approaches to assess the effects of Au, CuO,
and CdTe NP on the innate immune system. The human monocyte cell line
THP-1 was employed as a model. The anticancer drugs camptothecin and
doxorubicin were used as positive controls for cell death, and lipopolysaccharide
was chosen as a positive control for proinflammatory activation. Despite
equivalent overall toxicity effect (50 ± 10% dead cells), the
three NP induced distinctly different proteomics signatures, with
the strongest effect being induced by CdTe NP, followed by CuO and
gold NP. The CdTe toxicity mechanism involves down-regulation of topoisomerases.
The effect of CuO NP is most reminiscent of oxidative stress and involves
up-regulation of proteins involved in heat response. The gold NP induced
up-regulation of the inflammatory mediator, NF-κB, and its inhibitor
TIPE2 was identified as a direct target of gold NP. Furthermore, gold
NP triggered activation of NF-κB as evidenced by phosphorylation
of the p65 subunit. Overall, the combined proteomics approach described
here can be used to characterize the effects of NP on immune cells