Inhibition of jet fuel aliphatic hydrocarbon induced toxicity in human epidermal keratinocytes.
Jet propellant (JP)-8, the primary jet fuel used by the U.S. military, consists of hydrocarbon-rich kerosene base commercial jet fuel (Jet-A) plus additives DC1-4A, Stadis 450 and diethylene glycol monomethyl ether. Human epidermal keratinocytes (HEK) were exposed to JP-8, aliphatic hydrocarbon (HC) fuel S-8 and aliphatic HC pentadecane (penta), tetradecane (tetra), tridecane (tri) and undecane (un) for 5 min. Additional studies were conducted with signal transduction pathway blockers parthenolide (P; 3.0 microm), isohelenin (I; 3.0 microm), SB 203580 (SB; 13.3 microm), substance P (SP; 3.0 microm) and recombinant human IL-10 (rHIL-10; 10 ng ml(-1)). In the absence of inhibitors, JP-8 and to a lesser extent un and S-8, had the greatest toxic effect on cell viability and inflammation suggesting, as least in vitro, that synthetic S-8 fuel is less irritating than the currently used JP-8. Each inhibitor significantly (P < 0.05) decreased HEK viability. DMSO, the vehicle for P, I and SB, had a minimal effect on viability. Overall, IL-8 production was suppressed at least 30% after treatment with each inhibitor. Normalizing data relative to control indicate which inhibitors suppress HC-mediated IL-8 to control levels. P was the most effective inhibitor of IL-8 release; IL-8 was significantly decreased after exposure to un, tri, tetra and penta but significantly increased after JP-8 exposure compared with controls. Inhibitors were not effective in suppressing IL-8 release in JP-8 exposures to control levels. This study shows that inhibiting NF-kappa B, which appears to play a role in cytokine production in HC-exposed HEK in vitro, may reduce the inflammatory effect of HC in vivo.
Inman
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AO
Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27606, USA.
Monteiro-Riviere
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NA
Riviere
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JE
D000473:Alkanes / Q000633:toxicity*; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D006838:Hydrocarbons / Q000633:toxicity*; D007093:Imidazoles / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D007509:Irritants / Q000633:toxicity*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism; D013997:Time Factors
D000473:Alkanes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006838:Hydrocarbons; C508609:IL10 protein, human; D007093:Imidazoles; D007509:Irritants; C098607:JP8 aviation fuel; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011994:Recombinant Proteins; C534345:S-8 fuel; D012717:Sesquiterpenes; C103906:isohelenin; D016753:Interleukin-10; C002669:parthenolide; D013373:Substance P; C093642:SB 203580