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

Inman, Alfred O.; Monteiro‐Riviere, Nancy A.; Riviere, Jim E.

doi:10.1002/jat.1309

Cited by 9 publications

(7 citation statements)

References 46 publications

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“…3B), COX-2, and/ or immune suppression (Ramos et al, 2007) when we used synthetic jet fuel (S-8), which is devoid of aromatic hydrocarbons. Others however, have demonstrated that treating cultured human epidermal keratinocytes with S-8 induces the production of the inflammatory cytokines IL-6 and IL-8, and JP-8 INDUCES COX-2 VIA ROS AND NF-jb that cytokine production can be inhibited by parthenolide, implying a role for NF-jb (Inman et al, 2008). We suggest that the differences between our results and those reported by Inman and colleagues could be attributed to a number of factors.…”

Section: Discussioncontrasting

confidence: 72%

JP-8 Induces Immune Suppression via a Reactive Oxygen Species NF-κβ–Dependent Mechanism

Ramos

Limón-Flores

Ullrich

2008

Toxicological Sciences

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Applying jet fuel (JP-8) to the skin of mice induces immune suppression. JP-8-treated keratinocytes secrete prostaglandin E(2), which is essential for activating immune suppressive pathways. The molecular pathway leading to the upregulation of the enzyme that controls prostaglandin synthesis, cyclooxygenase (COX)-2, is unclear. Because JP-8 activates oxidative stress and because reactive oxygen species (ROS) turn on nuclear factor kappa B (NF-kappabeta), which regulates the activity of COX-2, we asked if JP-8-induced ROS and NF-kappabeta contributes to COX-2 upregulation and immune suppression in vivo. JP-8 induced the production of ROS in keratinocytes as measured with the ROS indicator dye, aminophenyl fluorescein. Fluorescence was diminished in JP-8-treated keratinocytes overexpressing catalase or superoxide dismutase (SOD) genes. JP-8-induced COX-2 expression was also reduced to background in the catalase and SOD transfected cells, or in cultures treated with N-acetylcysteine (NAC). When NAC was injected into JP-8-treated mice, dermal COX-2 expression, and JP-8-induced immune suppression was inhibited. Because ROS activates NF-kappabeta, we asked if this transcriptional activator played a role in the enhanced COX-2 expression and JP-8-induced immune suppression. When JP-8-treated mice, or JP-8-treated keratinocytes were treated with a selective NF-kappabeta inhibitor, parthenolide, COX-2 expression, and immune suppression were abrogated. Similarly, when JP-8-treated keratinocytes were treated with small interfering RNA specific for the p65 subunit of NF-kappabeta, COX-2 upregulation was blocked. These data indicate that ROS and NF-kappabeta are activated by JP-8, and these pathways are involved in COX-2 expression and the induction of immune suppression by jet fuel.

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Section: Discussioncontrasting

confidence: 72%

JP-8 Induces Immune Suppression via a Reactive Oxygen Species NF-κβ–Dependent Mechanism

Ramos

Limón-Flores

Ullrich

2008

Toxicological Sciences

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“…These include an anti-icing agent (diethylene glycol monomethyl ether [DGME]), an antistatic agent (Stadis 450), and an anticorrosive agent (DCI-4A), all of which are required additives, while the addition of metal chelators and antioxidants is allowed but not required (Inman et al, 2008; Ritchie et al, 2003). According to the Air Force Logistics Management Agency, DGME is found in JP-8 at a 1:1000 dilution, while DCI-4A and Stadis 450 are present at smaller concentrations (1:66,660 and 1:666,666 dilutions, respectively) (AFLMA, 2007).…”

Section: Discussionmentioning

confidence: 99%

Jet Fuel Kerosene is not Immunosuppressive in Mice or Rats Following Inhalation for 28 Days

White

DeLorme

Beatty

et al. 2013

Journal of Toxicology and Environmental Health, Part A

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Previous reports indicated that inhalation of JP-8 aviation turbine fuel is immunosuppressive. However, in some of those studies, the exposure concentrations were underestimated, and percent of test article as vapor or aerosol was not determined. Furthermore, it is unknown whether the observed effects are attributable to the base hydrocarbon fuel (jet fuel kerosene) or to the various fuel additives in jet fuels. The present studies were conducted, in compliance with Good Laboratory Practice (GLP) regulations, to evaluate the effects of jet fuel kerosene on the immune system, in conjunction with an accurate, quantitative characterization of the aerosol and vapor exposure concentrations. Two female rodent species (B6C3F1 mice and Crl:CD rats) were exposed by nose-only inhalation to jet fuel kerosene at targeted concentrations of 0, 500, 1000, or 2000 mg/m3 for 6 h daily for 28 d. Humoral, cell-mediated, and innate immune functions were subsequently evaluated. No marked effects were observed in either species on body weights, spleen or thymus weights, the T-dependent antibody-forming cell response (plaque assay), or the delayed-type hypersensitivity (DTH) response. With a few exceptions, spleen cell numbers and phenotypes were also unaffected. Natural killer (NK) cell activity in mice was unaffected, while the NK assessment in rats was not usable due to an unusually low response in all groups. These studies demonstrate that inhalation of jet fuel kerosene for 28 d at levels up to 2000 mg/m3 did not adversely affect the functional immune responses of female mice and rats.

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“…As we know, S-8, an aliphatic hydrocarbon (HC) fuel, is synthesized using the FT synthetic fuel process. Synthetic gas produced from natural gas, coal, or biomass is converted using heat and pressure into a clean burning liquid fuel made up of aliphatic HC (Inman et al, 2008). Its toxic effect may different with JP-8 due to its molecular weight, specific gravities, and compositions, with S-8 jet fuel containing alkane-rich hydrocarbons in the C7-C18 range and JP-8 jet fuel with aromatic hydrocarbons in the C9-C16 range.…”

Section: Discussionmentioning

confidence: 99%

“…Considering that S-8 is devoid of aromatic hydrocarbons, S-8 may have the higher threshold level at which damage occurs when compared with that of JP-8 jet fuel. Two recent dermal exposure studies have provided solid support for this speculation (Ramos et al, 2007;Inman et al, 2008). One applied S-8 alone to the skin of mice did not upregulate the expression of epidermal cyclooxygenase-2 (COX-2) nor does it induce immune suppression (Ramos et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pulmonary Evaluation of Permissible Exposure Limit of Syntroleum S-8 Synthetic Jet Fuel in Mice

Wong¹,

Thomas²,

Barbaris

et al. 2009

Toxicological Sciences

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No current studies have systematically examined pulmonary health effects associated with Syntroleum S-8 synthetic jet fuel (S-8). In order to gain an understanding about the threshold concentration in which lung injury is observed, C57BL/6 male mice were nose-only exposed to S-8 for 1 h/day for 7 days at average concentrations of 0 (control), 93, 352, and 616 mg/m(3). Evaluation of pulmonary function, airway epithelial barrier integrity, and pathohistology was performed 24 h after the final exposures. Significant decreases were detected in expiratory lung resistance and total lung compliance of the 352 mg/m(3) group, for which no clear concentration-dependent alterations could be determined. No significant changes in respiratory permeability were exhibited, indicating that there was no loss of epithelial barrier integrity following S-8 exposure. However, morphological examination and morphometric analysis of distal lung tissue, by using transmission electron microscopy, revealed cellular damage in alveolar type II epithelial cells, with significant increases in volume density of lamellar bodies/vacuoles at 352 and 616 S-8 mg/m(3). Moreover, terminal bronchiolar Clara injury, as evidenced by apical membrane blebs, was observed at relatively low concentrations, suggesting if this synthetic jet fuel is utilized, the current permissible exposure limit of 350 mg/m(3) for hydrocarbon fuels should cautiously be applied.

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

Cited by 9 publications

References 46 publications

JP-8 Induces Immune Suppression via a Reactive Oxygen Species NF-κβ–Dependent Mechanism

JP-8 Induces Immune Suppression via a Reactive Oxygen Species NF-κβ–Dependent Mechanism

Jet Fuel Kerosene is not Immunosuppressive in Mice or Rats Following Inhalation for 28 Days

Pulmonary Evaluation of Permissible Exposure Limit of Syntroleum S-8 Synthetic Jet Fuel in Mice

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