| The purpose of this research was to (1) identify potential changes in the expression of the pro-inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) in normal human epidemal keratinocytes (NHEK) exposed to the jet fuels Jet A, JP-8, and JP-8+100; (2) repeat these studies in primary porcine keratinocytes (PKC) and immortalized porcine keratinocytes (MSK 3877) and compare their results to those of NHEK for the purpose of creating an alternative in vitro animal model; and (3) determine if specific aliphatic hydrocarbon components common to all three fuels are partially responsible for the alterations seen in IL-8.; NHEK dosed with 0.1% jet fuels (Jet A, JP8, and JP8+100) were found to release both TNF-α and IL-8. IL-8 release was noted within 8 hr and continued to rise through 24 hr, while maximal levels of TNF-α release were seen at 4hr. mRNA for IL-8 was elevated 4hr following exposure. PKC exposed to jet fuels caused a slight upregulation of TNF-α mRNA at early time points, but no significant differences in TNF-α protein production were detected. IL-8 mRNA was increased at 4 hr following exposure, and IL-8 protein was increased at 8 hr. In MSK 3877 cells, jet fuels increased the production and expression of TNF-α mRNA and protein. In contrast, IL-8 mRNA was only slightly induced compared to control. IL-8 protein release was suppressed by jet fuel exposure. Some similarities exist between PKC and NHEK with respect to both TNF-α and IL-8 production, and the expression profile of TNF-α in MSK3877 cells mimics that of NHEK, but the profile of IL-8 expression opposes that of PKC and NHEK.; In order to study some of the individual components of jet fuels, NHEK were exposed to four aliphatic hydrocarbons solubilized in α-cyclodextrin (undecane, dodecane, tridecane, hexadecane). These hydrocarbons caused a significant increase in IL-8 release at subtoxic concentrations of the aliphatic hydrocarbons (<62.5μM). |
