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MECHANISMS OF NANODIAMOND PARTICLE INDUCED IL-8 EXPRESSION IN HUMAN AIRWAY EPITHELIAL CELLS
Citation:
SILBAJORIS, R. A., L. A. DAILEY, J. M. SAMET, W. CHENG, AND P. A. BROMBERG. MECHANISMS OF NANODIAMOND PARTICLE INDUCED IL-8 EXPRESSION IN HUMAN AIRWAY EPITHELIAL CELLS. Presented at Society of Toxicology 47th Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
research results
Description:
Nanodiamond particles (NDP) prepared by detonation under confined conditions 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 biomedical applications such as drug delivery. Separate studies have shown that elemental carbon particles that simulate the carbonaceous core of combustion derived airborne particulate matter can induce inflammatory responses in the lung through the generation of reactive oxygen species. To assess the respiratory effects 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 μg/ml NDP (average particle diameter of 5 nm and surface area ~300 m2/g) resulted in IL-8 mRNA increases up to 100-fold over resting levels and was accompanied by up to 13-fold increases in IL-8 protein levels in the media. Transfections with IL-8 promoter constructs showed that exposure to NDP increases IL-8 transcriptional activity. Separate experiments indicated that HAEC avidly take up NDP and that this uptake can be blocked with cytochalasin D. Furthermore, cytochalasin D also abrogated NDP induced IL-8 mRNA levels. NDP-induced IL-8 expression was blunted by overexpression of catalase, and to a lesser extent SOD, in HAEC. We conclude that NDP induce IL-8 expression via a transcriptional mechanism that requires particle uptake and involves the formation of reactive oxygen species. These data are evidence of an inflammatory response to NDP exposure in human lung cells. THIS ABSTRACT OF A PROPOSED PRESENTATION DOES NOT NECESSARILY REFLECT EPA POLICY.