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Abstract
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.
Document Type
Article
Publication Date
5-14-2013
Digital Object Identifier (DOI)
http://dx.doi.org/10.1371/journal.pone.0063159
Repository Citation
Zhang, Bei; Choi, Jeong June; Eum, Sung Yong; Daunert, Sylvia; and Toborek, Michal, "TLR4 Signaling is Involved in Brain Vascular Toxicity of PCB153 Bound to Nanoparticles" (2013). Graduate Center for Nutritional Sciences Faculty Publications. 3.
https://uknowledge.uky.edu/nutrisci_facpub/3
Notes/Citation Information
Published in PLOS One, v. 8, issue. 5, e63159.
© 2013 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
9 Jan 2014: Zhang B, Choi JJ, Eum SY, Daunert S, Toborek M (2014) Correction: TLR4 Signaling Is Involved in Brain Vascular Toxicity of PCB153 Bound to Nanoparticles.PLoS ONE 9(1): 10.1371/annotation/e34adc2a-f73a-4055-8519-fa2deb2e852f. doi: 10.1371/annotation/e34adc2a-f73a-4055-8519-fa2deb2e852f | View correction