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Dive into the research topics where Gregory K. DeKrey is active.

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Featured researches published by Gregory K. DeKrey.


Toxicology and Applied Pharmacology | 2010

Endosulfan induces CYP2B6 and CYP3A4 by activating the pregnane X receptor.

Richard Ct Casabar; Parikshit C. Das; Gregory K. DeKrey; Catherine S. Gardiner; Yan Cao; Randy L. Rose; Andrew D. Wallace

Endosulfan is an organochlorine pesticide commonly used in agriculture. Endosulfan has affects on vertebrate xenobiotic metabolism pathways that may be mediated, in part, by its ability to activate the pregnane X receptor (PXR) and/or the constitutive androstane receptor (CAR) which can elevate expression of cytochrome P450 (CYP) enzymes. This study examined the dose-dependency and receptor specificity of CYP induction in vitro and in vivo. The HepG2 cell line was transiently transfected with CYP2B6- and CYP3A4-luciferase promoter reporter plasmids along with human PXR (hPXR) or hCAR expression vectors. In the presence of hPXR, endosulfan-alpha exposure caused significant induction of CYP2B6 (16-fold) and CYP3A4 (11-fold) promoter activities over control at 10 microM. The metabolite endosulfan sulfate also induced CYP2B6 (12-fold) and CYP3A4 (6-fold) promoter activities over control at 10 microM. In the presence of hCAR-3, endosulfan-alpha induced CYP2B6 (2-fold) promoter activity at 10 microM, but not at lower concentrations. These data indicate that endosulfan-alpha significantly activates hPXR strongly and hCAR weakly. Using western blot analysis of human hepatocytes, the lowest concentrations at which CYP2B6 and CYP3A4 protein levels were found to be significantly elevated by endosulfan-alpha were 1.0 microM and 10 microM, respectively. In mPXR-null/hPXR-transgenic mice, endosulfan-alpha exposure (2.5mg/kg/day) caused a significant reduction of tribromoethanol-induced sleep times by approximately 50%, whereas no significant change in sleep times was observed in PXR-null mice. These data support the role of endosulfan-alpha as a strong activator of PXR and inducer of CYP2B6 and CYP3A4, which may impact metabolism of CYP2B6 or CYP3A4 substrates.


Infection and Immunity | 2001

Influence of Costimulatory Molecules on Immune Response to Leishmania major by Human Cells In Vitro

Cláudia Brodskyn; Gregory K. DeKrey; Richard G. Titus

ABSTRACT The importance of CD40, CD80, and CD86 costimulatory molecules in anti-Leishmania immune responses has been established in murine models. A role for these costimulatory molecules in human anti-Leishmania immune responses was investigated in this study. Autologous macrophages and peripheral blood leukocytes (PBL) were prepared from peripheral blood mononuclear cells ofLeishmania-naive donors and cultured with or withoutLeishmania major in various combinations. After 7 days of culture, high levels of CD40 and CD86 were expressed on macrophages in the presence or absence of L. major. When macrophages were cultured for an additional 7 days with PBL, expression of all three costimulatory molecules was detected. When L. major was present in these cultures, the expression of CD80, and to a lesser extent CD40, on macrophages was enhanced. Blockade of CD80, CD86, or both molecules (in the order of greatest effect) in cultures containing macrophages, PBL, and L. major significantly inhibited the production of gamma interferon, interleukin-5 (IL-5), and IL-12. Blockade of CD40-CD154 interactions also significantly inhibited production of these cytokines in response to L. major. Production of IL-10 was unaltered by the blockade of these costimulatory molecules. Thus, these data suggest that CD40, CD80, and CD86 expression and regulation may significantly impact anti-Leishmania immune responses in humans.


Toxicon | 2011

A comparative study of the effects of venoms from five rear-fanged snake species on the growth of Leishmania major: Identification of a protein with inhibitory activity against the parasite

María E. Peichoto; Flávio L. Tavares; Gregory K. DeKrey; Stephen P. Mackessy

Leishmania parasites of several species cause cutaneous and visceral disease to millions of people worldwide, and treatment for this vector-borne protozoan parasite typically involves administration of highly toxic antimonial drugs. Snake venoms are one of the most concentrated enzyme sources in nature, displaying a broad range of biological effects, and several drugs now used in humans were derived from venoms. In this study, we compared the effects of the venoms of the South American rear-fanged snakes Philodryas baroni (PbV), Philodryas olfersii olfersii (PooV) and Philodryas patagoniensis (PpV), and the North American rear-fanged snakes Hypsiglena torquata texana (HttV) and Trimorphodon biscutatus lambda (TblV), on the growth of Leishmania major, a causative agent of cutaneous leishmaniasis. Different concentrations of each venom were incubated with the log-phase promastigote stage of L. major. TblV showed significant anti-leishmanial activity (IC₅₀ of 108.6 μg/mL) at its highest concentrations; however, it induced parasite proliferation at intermediate concentrations. PpV was not very active in decreasing the parasitic growth, and a high final concentration (1.7 mg/mL) was necessary to inhibit proliferation by only 51.5% ± 3.6%. PbV, PooV and HttV, at final concentrations of 562, 524 and 438 μg/mL respectively, had no significant effect on L. major growth. The phospholipase A₂ of TblV (trimorphin) was isolated and assayed as for crude venom, and it also exhibited dose-dependent biphasic effects on the parasite culture, with potent cytotoxicity at higher concentrations (IC₅₀ of 0.25 μM; 3.6 μg/mL) and stimulation of proliferation at very low concentrations. Anti-leishmanial activity of TblV appears to be solely due to the action of trimorphin. This is the first report of anti-leishmanial activity of rear-fanged snake venoms, and these results suggest novel possibilities for discovering new protein-based drugs that might be used as possible agents against leishmaniasis as well as tools to study the biology of Leishmania parasites.


Infection and Immunity | 2001

Interleukin-6 Deficiency Influences Cytokine Expression in Susceptible BALB Mice Infected with Leishmania major but Does Not Alter the Outcome of Disease

Richard G. Titus; Gregory K. DeKrey; Robin V. Morris; Milena B. P. Soares

ABSTRACT Since interleukin-6 (IL-6) may promote Th2 responses, we infected BALB IL-6-deficient (IL-6−/−) mice with Leishmania major. There was not a significant difference between the courses of infection (lesion size and parasite burden) in IL-6−/− and wild-type mice, but IL-6−/−mice expressed lower levels of Th2- and Th1-associated cytokines.


Reproductive Toxicology | 2015

Time- and dose-dependent effects of ethanol on mouse embryonic stem cells.

Sarah L. Worley; Brittney Vaughn; Alexander I. Terry; Catherine S. Gardiner; Gregory K. DeKrey

Ethanol is a common solvent used with mouse embryonic stem (mES) cells in protocols to test chemicals for evidence of developmental toxicity. In this study, dose-response relationships for ethanol toxicity in mES cells were examined. For cells maintained in an undifferentiated state, ethanol significantly reduced viable cell numbers with estimated half maximal inhibitory concentrations of 1.5% and 0.8% ethanol after 24 and 48h, respectively, observations which correlated with significantly increased expression of apoptotic markers. For cells cultured to induce cardiomyocyte formation, up to 0.5% ethanol during the first two days failed to alter the outcome of differentiation, whereas 0.3% ethanol for 11 days significantly reduced the fraction of cultures containing contracting areas, an observation that correlated with significantly reduced cell numbers. These results suggest that ethanol is not an inert solvent at concentrations that might be used for developmental toxicity testing.


PLOS ONE | 2013

2,3,7,8-Tetrachlorodibenzo-p-dioxin Slows the Progression of Experimental Cutaneous Leishmaniasis in Susceptible BALB/c and SCID Mice

Gregory K. DeKrey; Riane E. Teagarden; Jerica L. Lenberg; Richard G. Titus

In a model of experimental cutaneous leishmaniasis, pre-exposure of Leishmania major-resistant mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor agonist, causes suppression of the protective anti-parasite T helper 1 response while paradoxically also reducing parasite burdens in those animals. In this study, we examined if TCDD exposure could also reduce parasite burdens in L. major-susceptible BALB/c mice. In the highest dose group (160 µg/Kg), TCDD treatment caused a significant reduction of parasite burdens by 10-fold after three weeks while also causing a significant lymphoid atrophy indicating suppression of the non-protective T helper 2 response. A dose-dependent delay of foot lesion progression was also observed such that lesion size in the highest dose group was less than half that of controls after 35 days of infection. Importantly, although TCDD exposure initially reduced disease severity and prolonged the course of disease by as much as three fold in some animals, this effect was transitory and TCDD did not induce resistance to L. major infection. Because TCDD exposure reduced L. major burdens in both resistant and susceptible mice, we hypothesized that TCDD reduces L. major burdens in mice by a mechanism that does not involve adaptive immunity. To test this, severe combined immunodeficient (SCID) mice were used. In mice infected with a moderate number of L. major (10,000), TCDD treatment caused a time- and dose-dependent decrease of parasite burdens by nearly 100-fold after six weeks in the highest dose group (200 µg/Kg). A significant and dose-dependent delay of foot lesion progression was also observed in these animals. These results indicate that TCDD exposure can reduce the severity of leishmanial disease in mice independent of adaptive immunity.


Toxicology reports | 2018

Effects of endosulfan isomers on cytokine and nitric oxide production by differentially activated RAW 264.7 cells

Alexander I. Terry; Sandra Benitez-Kruidenier; Gregory K. DeKrey

Graphical abstract


Infection and Immunity | 1998

Analysis of the Immune Responses of Mice to Infection with Leishmania braziliensis

Gregory K. DeKrey; Hermênio Cavalcante Lima; Richard G. Titus


Reproductive Toxicology | 2005

Effects of paraquat on development of preimplantation embryos in vivo and in vitro

Mellisa A. Hausburg; Gregory K. DeKrey; James J. Salmen; Michelle R. Palic; Catherine S. Gardiner


Journal of Pharmacology and Experimental Therapeutics | 1995

Effects of exogenous corticosterone treatment on alloantigen-specific cytotoxic T lymphocyte activity in mice.

Gregory K. DeKrey; N I Kerkvliet

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Catherine S. Gardiner

University of Northern Colorado

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Alexander I. Terry

University of Northern Colorado

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Andrew D. Wallace

North Carolina State University

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Brittney Vaughn

University of Northern Colorado

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Richard Ct Casabar

North Carolina State University

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Alex Terry

University of Northern Colorado

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Erin A Lively

North Carolina State University

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Flávio L. Tavares

University of Northern Colorado

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