Journal
BIOMATERIALS
Volume 100, Issue -, Pages 67-75Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.05.021
Keywords
High-density lipoprotein-like nanoparticle; Lipopolysaccharide; Endotoxin; Toll-like receptor 4; Inflammatory response
Funding
- Howard Hughes Medical Institute (HHMI)
- National Institutes of Health/National Cancer Institute [U54CA151880, R01CA167041]
- Department of Defense/Air Force Office of Scientific Research [FA95501310192]
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Toll-like receptor 4 (TLR4) plays a critical role in the innate immune system. Stimulation of TLR4 occurs upon binding lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls. Due to the potency of the induced inflammatory response, there is a growing interest in agents that can most proximally modulate this LPS/TLR4 interaction to prevent downstream cell signaling events and the production of inflammatory mediators. Building on the natural ability of human high-density lipoprotein (HDL) to bind LPS, we synthesized a suite of HDL-like nanoparticles (HDL-like NP). We identified one HDL-like NP that was particularly effective at decreasing TLR4 signaling caused by addition of purified LPS or Gram-negative bacteria to model human cell lines or primary human peripheral blood cells. The HDL-like NP functioned to inhibit TLR4-dependent inflammatory response to LPS derived from multiple bacterial species. Mechanistically, data show that the NP mainly functions by scavenging and neutralizing the LPS toxin. Taken together, HDL-like NPs constitute a powerful endotoxin scavenger with the potential to significantly reduce LPS-mediated inflammation. (C) 2016 Elsevier Ltd. All rights reserved.
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