Endotoxin potentiation of trichothecene-induced lymphocyte apoptosis is mediated by up-regulation of glucocorticoids

Toxicology and Applied Pharmacology
Zahidul IslamJ J Pestka

Abstract

Exposure to bacterial endotoxin (lipopolysaccharide, LPS) is quite common and may increase human susceptibility to chemical-induced tissue injury. The purpose of this study was to identify mechanisms by which LPS potentiates lymphoid tissue depletion in B6C3F1 mice exposed to the common food-borne trichothecene mycotoxin, vomitoxin (VT). As demonstrated by DNA fragmentation and flow cytometric analysis, apoptosis in thymus, Peyer's patches, and bone marrow was marked in mice 12 h after administering Escherichia coli LPS (0.1 mg/kg body wt ip) concurrently with VT (12.5 mg/kg body wt po), whereas apoptosis in control mice or mice treated with either toxin alone was minimal. Based on observed increases in tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 serum concentrations following LPS and VT cotreatment, the roles of these cytokines in apoptosis potentiation were assessed. Injection with rolipram, an inhibitor of TNF-alpha expression, or use of IL-6 knockout mice was ineffective at impairing thymic apoptosis induction by the toxin cotreatment, suggesting that these cytokines did not mediate LPS potentiation. Toxin cotreatment increased splenic cyclooxygenase-2 mRNA expression, suggesting possible involvement of p...Continue Reading

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Citations

Jun 2, 2012·Nutrition Research Reviews·Paul C TurnerJames Pestka
Mar 15, 2005·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·James J Pestka, Alexa T Smolinski
Jun 19, 2004·Journal of Toxicology and Environmental Health. Part a·Winfried DrochnerMartin Steffl
Jan 16, 2010·Journal of Toxicology and Environmental Health. Part a·Zahidul IslamJames J Pestka
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Sep 30, 2003·Journal of Toxicology and Environmental Health. Part a·Yuseok MoonJames J Pestka
Nov 17, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·James J PestkaJack R Harkema
Jun 7, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Zahidul IslamJames J Pestka
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Jun 17, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Maoxiang LiJames Pestka
Mar 22, 2003·Toxicology and Applied Pharmacology·Yuseok Moon, James J Pestka
Nov 5, 2003·Chemico-biological Interactions·Rebecca L UzarskiJames J Pestka
Dec 24, 2003·The Journal of Nutritional Biochemistry·Yuseok Moon, James J Pestka

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