Nanodiamond particles induce Il-8 expression through a transcript stabilization mechanism in human airway epithelial cells

Nanodiamond particles (NDP) prepared by detonational processes have a number of industrial and analytical applications. Previous in vitro studies have reported NDP to be biologically inert with negligible cytotoxicity, implying that they are potentially suitable for novel drug delivery applications. Separate studies, however, have shown that elemental carbon particles, a material closely related to NDP, can induce inflammatory responses in the lung. To assess the potential toxicity of exposure to NDP, we examined its effects on IL-8 expression by human airway epithelial cells (HAEC) in vitro. Four-hour exposures of HAEC to 66 mu g/ml NDP resulted in IL-8 mRNA increases up to 70-fold over control levels and were accompanied by up to 14-fold increases in IL-8 protein levels in the media. Adenoviral overexpression of catalase significantly reduced NDP-induced IL-8 mRNA expression in HAEC. Interestingly, exposure to NDP did not increase IL-8 transcriptional activity, as measured with the use of IL-8 promoter reporter constructs. Rather, NDP treatment was found to markedly increase the half-life of IL8-mRNA transcripts in HAEC. These findings show a pronounced increase in the expression of IL-8 in HAEC, suggesting that NDP inhalation can cause inflammatory responses in the human lung.