| First Author | Zhang B | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 5 | Pages | e63159 |
| PubMed ID | 23690990 | Mgi Jnum | J:202173 |
| Mgi Id | MGI:5517621 | Doi | 10.1371/journal.pone.0063159 |
| Citation | Zhang B, et al. (2013) TLR4 signaling is involved in brain vascular toxicity of PCB153 bound to nanoparticles. PLoS One 8(5):e63159 |
| abstractText | PCBs bind to environmental particles; however, potential toxicity exhibited by such complexes is not well understood. The aim of the present study is to study the hypothesis that assembling onto nanoparticles can influence the PCB153-induced brain endothelial toxicity via interaction with the toll-like receptor 4 (TLR4). To address this hypothesis, TLR4-deficient and wild type control mice (males, 10 week old) were exposed to PCB153 (5 ng/g body weight) bound to chemically inert silica nanoparticles (PCB153-NPs), PCB153 alone, silica nanoparticles (NPs; diameter, 20 nm), or vehicle. Selected animals were also subjected to 40 min ischemia, followed by a 24 h reperfusion. As compared to exposure to PCB153 alone, treatment with PCB153-NP potentiated the brain infarct volume in control mice. Importantly, this effect was attenuated in TLR4-deficient mice. Similarly, PCB153-NP-induced proinflammatory responses and disruption of tight junction integrity were less pronounced in TLR4-deficient mice as compared to control animals. Additional in vitro experiments revealed that TLR4 mediates toxicity of PCB153-NP via recruitment of tumor necrosis factor-associated factor 6 (TRAF6). The results of current study indicate that binding to seemingly inert nanoparticles increase cerebrovascular toxicity of PCBs and suggest that targeting the TLR4/TRAF6 signaling may protect against these effects. |
