Superinduction of IL-2 gene expression by vomitoxin (deoxynivalenol) involves increased mRNA stability

Toxicology and Applied Pharmacology
S LiJ J Pestka

Abstract

To better understand molecular mechanisms by which the trichothecene vomitoxin (VT) superinduces cytokine gene expression, we studied the posttranscriptional effects of this mycotoxin on interleukin-2 (IL-2) gene expression in murine EL-4 thymoma cells stimulated with phorbol 12-myristate 13-acetate and ionomycin (PMA + ION). Northern analysis revealed that doses of 50 to 500 ng/ml VT superinduced IL-2 mRNA expression in a dose- and time-dependent manner in a synchronous model where VT was added at onset of PMA + ION stimulation. In accordance with the mRNA levels, IL-2 production was significantly elevated in the presence of 50 to 250 ng/ml VT. Superinduction of IL-2 mRNA was also observed in a delayed synchronous model (VT added 20 hr after PMA + ION stimulation) and an asynchronous model (VT added 20 hr after PMA + ION stimulation and removal). To assess the effects of VT (500 ng/ml) on IL-2 mRNA half-life, three transcriptional inhibitors were used in the delayed synchronous model. Actinomycin D (ActD) had a pronounced stabilizing effect on IL-2 mRNA but not on mRNA for the housekeeping gene GAPDH. VT did not affect IL-2 mRNA levels in ActD-treated cells. Although 5,6-dichloro-beta-D-ribofuranosyl-benzimidazole (DRB) also h...Continue Reading

Citations

Feb 25, 2009·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·J J Pestka
Mar 15, 2005·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·James J Pestka, Alexa T Smolinski
Sep 17, 2004·Journal of Toxicology and Environmental Health. Part a·Shawn KinserJames Pestka
Jan 5, 2002·Biological Chemistry·A AbudulaB Wiederanders
May 24, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·G Le DréanD Parent-Massin
Mar 18, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hui-Ren ZhouJames J Pestka
Jul 20, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jennifer S Gray, James J Pestka
Jun 17, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Maoxiang LiJames Pestka
Jul 4, 2001·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·F A MekyC P Wild
Jan 27, 2004·Biochemical and Biophysical Research Communications·Zhangfei ShouKaoru Miyamoto
Dec 24, 2003·The Journal of Nutritional Biochemistry·Yuseok Moon, James J Pestka
Mar 2, 2010·Prostaglandins, Leukotrienes, and Essential Fatty Acids·James J Pestka

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