Cytokine induction as a measure of cutaneous toxicity in primary and immortalized porcine keratinocytes exposed to jet fuels, and their relationship to normal human epidermal keratinocytes

The purpose of this study was to identify biomarkers of toxicity in primary porcine keratinocytes (PKC) and an immortalized porcine keratinocyte cell line (MSK3877) exposed to jet fuels Jet A, JP-8, and JP-8 + 100. Cells were exposed to 0.1% jet fuels and assayed for interleukin-8 (IL-8) and tumor n ecrosis factor alpha (TNF-alpha) mRNA using the TaqMan real time quantitati ve reverse transcriptase PCR assay. IL-8 and TNF-alpha protein release was measured using an ELISA. PKC exposed to jet fuels caused a slight upregulat ion of TNF-alpha mRNA at early time points, but no significant differences in TNF-alpha protein production were detected. IL-8 mRNA was increased at 4 h following exposure, and IL-s protein was increased at 8 h. In MSK 3877 c ells, jet fuels were shown to increase the production and expression of TNF -alpha mRNA and protein at 30 min and I h following exposure, respectively. IL-s mRNA was only slightly induced compared to control. IL-8 protein rele ase was suppressed by jet fuel exposure. These results were compared with t hose of a previous study in our laboratory to evaluate the utility of using porcine cells in lieu of normal human epidermal keratinocytes (NHEK). Simi larities exist between PKC and NHEK with respect to both TNF-alpha and IL-8 production. The expression profile of TNF-alpha in MSK3877 cells mimics th at of NHEK. In contrast, the profile of IL-8 expression opposes that of PKC and NHEK. These results suggest that porcine keratinocytes are susceptible to jet fuel toxicity. However, the responses of immortalized cells may var y from those of PKC and NHEK necessitating cautious interpretation of such data. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.