Inhibition of jet fuel aliphatic hydrocarbon induced toxicity in human epidermal keratinocytes.

Abstract

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.

• Authors: A O Inman, N A Monteiro-Riviere, J E Riviere
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 28 Issue 4 Pg. 543-53 (May 2008) ISSN: 0260-437X [Print] England
• PMID: 17966119 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright (c) 2007 John Wiley & Sons, Ltd.

Chemical References

• Alkanes
• Anti-Inflammatory Agents
• Cytokines
• Hydrocarbons
• IL10 protein, human
• Imidazoles
• Irritants
• JP8 aviation fuel
• NF-kappa B
• Protein Kinase Inhibitors
• Pyridines
• Recombinant Proteins
• S-8 fuel
• Sesquiterpenes
• isohelenin
• Interleukin-10
• parthenolide
• Substance P
• SB 203580

Topics

• Alkanes (toxicity)
• Anti-Inflammatory Agents (metabolism, pharmacology)
• Cell Survival (drug effects)
• Cells, Cultured
• Cytokines (metabolism)
• Humans
• Hydrocarbons (toxicity)
• Imidazoles (pharmacology)
• Interleukin-10 (metabolism)
• Irritants (toxicity)
• Keratinocytes (drug effects, metabolism, pathology)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Pyridines (pharmacology)
• Recombinant Proteins (metabolism)
• Sesquiterpenes (pharmacology)
• Substance P (metabolism)
• Time Factors