Cerium dioxide nanoparticles selectively up-regulate C-C chemokine receptor 2 and CD16 expression on human monocytes

Abstract

Abstract Cerium dioxide nanoparticles (CeO2 NPs) are known as scavengers of reactive oxygen species for the coexistence of Ce3+/ Ce4+ oxidation states. Cell treatments with CeO2 NPs often lead to controversial pro-inflammatory and anti-inflammatory results. The aim of the study was to investigate the immune events following the administration of ceria nanoparticles to THP-1 monocytes. To address this issue, we performed flow cytometry, chemotaxis and ELISA experiments on THP-1 monocytes treated with different concentrations of CeO2 NPs. CeO2 nanoparticle treatments induced a significant pro-inflammatory C-C chemokine receptor 2 (CCR2) up-regulation within the first 6 hours lasting over-expressed for 24 hours. Differently, CCR5 showed no response at any concentration tested. Enhanced chemotaxis towards the CCR2 specific ligand MCP-1 reinforced the observation demonstrating a functional immune outcome. The pro-inflammatory profile of the treated monocytes was also supported by CD16 up-regulation but no differences in CX3CR1 or other monocyte receptors, like CD11b and CD14, were detectable. Moreover, CeO2 NPs exposure did not promote any release of inflammatory cytokines suggesting a specific and direct effect of the nanoparticles on CCR2 and CD16. Our in vitro results reveal a specific role of CeO2 NPs in the up-regulation of CCR2, which might contribute to increase the pro-inflammatory monocyte/macrophage migration toward the sites of CCL2 expression.