Nanodiamond particles induce I1-8 expression through a transcript stabilization mechanism in human airway epithelial cells

Abstract

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 mg/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.

Organic extracts from African dust storms stimulate oxidative stress and induce inflammatory responses in human lung cells through Nrf2 but not NF-κB

“…This interleukin is known to be sensitive to changes in redox potential containing an ARE-like element in its promoter region (Zhang et al, 2005). The molecular basis of Nrf2- mediated IL-8 production has been reported to be mainly through enhanced mRNA stability (Silbajoris et al, 2009; Zhang et al, 2005). …”

Mutagenicity and oxidative damage induced by an organic extract of the particulate emissions from a simulation of the deepwater horizon surface oil burns

“…HMOX1 expression is regulated tightly at the transcriptional level by the Kelch‐like ECH‐associated protein 1/nuclear erythroid 2‐related factor 2/antioxidant response element (KEAP1/Nrf2/ARE) pathway, which is induced by cellular exposure to a broad variety of electrophilic and oxidative stressors [Buendia et al, ; Lambros and Plafker, ; Loboda et al, ]. We have shown previously that exposure of human airway epithelial cells to environmental electrophiles found in ambient air induces the expression of HMOX1 through an oxidant dependent mechanism [Silbajoris et al, ; Cheng et al, ; Wages et al, ].…”

“…We designed the oligonucleotides using a primer‐design program (Primer Express, Applied Biosystems) obtained from Integrated DNA Technologies (Coralville, IA). We normalized the data to β‐ACTIN mRNA levels [Silbajoris et al, ; Cheng et al, ; Wages et al, ], which were not found to change in response to treatment with the oil‐burn extract.…”

“…We assessed the effect of the extract on extracellular flux of mitochondrial respiration in cultured human airway epithelial cells (BEAS‐2B), as well as on expression of the heme oxygenase ( HMOX1 ) gene. We have shown previously that HMOX1 expression, a marker of oxidative stress in mammalian cells, is induced by a wide variety of air pollutants [Silbajoris et al, ; Cheng et al, ; Wages et al, ].…”

Nanodiamonds and Their Applications in Cells

“…Nevertheless, it was shown to be either a minor or a transient effect as there were no significant alterations in downstream biological factors observed and one of the author's explanation concerns the highly sensitive cell model that was used in their research. An increase in inflammatory gene expression was found in human lung cells, suggesting the capability of NDs to cause an inflammatory response …”