Quantum dots induced monocyte chemotactic protein-1 expression via MyD88-dependent Toll-like receptor signaling pathways in macrophages

Toxicology. 2013 Jun 7:308:1-9. doi: 10.1016/j.tox.2013.03.003. Epub 2013 Mar 15.

Abstract

Quantum dots (QDs) are nano-sized semiconductors. Previously, intratracheal instillation of QD705s induces persistent inflammation in mouse lungs. In our present study, QD705-COOH and QD705-PEG activated NF-κB and increased monocyte chemotactic protein-1 (MCP-1) expression in macrophages RAW264.7 via MyD88 dependent Toll-like receptor (TLR) signaling pathways. MyD88 is an adapter protein for most TLRs to activate NF-κB. Silencing expression of MyD88 or p65 with siRNA or co-treatment with a NF-κB inhibitor tremendously abolished QD705s-induced NF-κB activity and MCP-1 expression. The involved TLRs might locate either on the cell surface or inside of cells. Co-treatment with a TLR4 inhibitor completely prevented MCP-1 induction by QD705-PEG. Nevertheless, QD705-COOH readily entered cells, and co-treatment with either inhibitors of endocytosis or intracellular TLRs prevented MCP-1 induction. These findings indicate that, depending on their surface modification, OD705s activate MyD88 dependent-TLRs at the surface or inside of the cells, which is an important mechanism for nanoparticles-induced inflammatory responses. But other MyD88-independent pathways may also involve in these responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chemokine CCL2 / biosynthesis*
  • Chemokine CCL2 / genetics
  • Chromogenic Compounds / pharmacology*
  • Gene Expression Regulation / drug effects
  • Macrophages / metabolism*
  • Mice
  • Myeloid Differentiation Factor 88 / biosynthesis
  • Myeloid Differentiation Factor 88 / physiology*
  • Particle Size
  • Quantum Dots*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Toll-Like Receptors / physiology*

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Chromogenic Compounds
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Toll-Like Receptors