Enhancement of lipopolysaccharide-induced nitric oxide and interleukin-6 production by PEGylated gold nanoparticles in RAW264.7 cells.

While the immunogenicity and cytotoxicity of gold nanoparticles (AuNPs) are noted by many researchers, the mechanisms by which AuNPs exert these effects are poorly understood. In this study, we investigated the effects of polyethylene glycolylated AuNPs (PEG@AuNPs) on lipopolysaccharide (LPS)-induced nitric oxide (NO) and interleukin-6 (IL-6) production and the associated molecular mechanism in RAW264.7 cells. The results showed that PEG@AuNPs were internalized more quickly by LPS-activated RAW264.7 cells than unstimulated cells, and they reached saturation within 24 hours. PEG@AuNPs enhanced LPS-induced production of NO and IL-6 and inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells, partially by activating p38 mitogen-activated protein kinases (p38 MAPK) and nuclear factor-kappaB pathways. In addition, the p38 MAPK inhibitor SB203580 attenuated PEG@AuNP-enhanced LPS-induced NO production and iNOS expression. Overproduction of NO and IL-6 is known to be closely correlated with the pathology of many diseases and inflammations. Thus, it is speculated that the highly biocompatible gold nanoparticles can induce immunotoxicity due to their potency to stimulate macrophages to release aberrant or excessive pro-inflammatory mediators.