TLR4 Signaling Is Involved in Brain Vascular Toxicity of PCB153 Bound to Nanoparticles

Bei Zhang, Jeong June Choi, Sung Yong Eum, Sylvia Daunert, Michal J Toborek

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article numbere63159
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 14 2013

Fingerprint

Toll-Like Receptor 4
nanoparticles
blood vessels
Nanoparticles
Blood Vessels
Toxicity
Brain
toxicity
brain
Polychlorinated Biphenyls
Silicon Dioxide
Tumor Necrosis Factor-alpha
tumor necrosis factors
mice
silica
Tight Junctions
Animals
Reperfusion
tight junctions
Ischemia

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

TLR4 Signaling Is Involved in Brain Vascular Toxicity of PCB153 Bound to Nanoparticles. / Zhang, Bei; Choi, Jeong June; Eum, Sung Yong; Daunert, Sylvia; Toborek, Michal J.

In: PLoS One, Vol. 8, No. 5, e63159, 14.05.2013.

Research output: Contribution to journalArticle

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