ELEVATED GENE-EXPRESSION AND PRODUCTION OF INTERLEUKIN-2, INTERLEUKIN-4, INTERLEUKIN-5, AND INTERLEUKIN-6 DURING EXPOSURE TO VOMITOXIN (DEOXYNIVALENOL) AND CYCLOHEXIMIDE IN THE EL-4 THYMOMA
Wm. Dong et al., ELEVATED GENE-EXPRESSION AND PRODUCTION OF INTERLEUKIN-2, INTERLEUKIN-4, INTERLEUKIN-5, AND INTERLEUKIN-6 DURING EXPOSURE TO VOMITOXIN (DEOXYNIVALENOL) AND CYCLOHEXIMIDE IN THE EL-4 THYMOMA, Toxicology and applied pharmacology, 127(2), 1994, pp. 282-290
Aberrant elevation of serum IgA and induction of murine IgA nephropath
y following dietary exposure to the naturally occurring trichothecene
vomitoxin (VT or deoxynivalenol) may involve dysregulation of cytokine
production at the T cell level. EL4.IL-2 (EL-4), a cloned thymoma tha
t produces interleukins (IL)-2, 4, 5, and 6, was used as a T cell mode
l to investigate the in vitro effects of VT on interleukin production
and gene expression. When supernatants of cells stimulated with phorbo
l 12-myristate 13-acetate (PMA) were assessed by enzyme-linked immunos
orbent assay, IL-2, 4, and 5 were increased in the presence of 50 and/
or 100 ng/ml VT for 2 and/or 8 days of culture. IL-2, 5, and 6 were al
so significantly elevated in the presence of 10-100 ng/ml of cyclohexi
mide (CHX), another protein synthesis inhibitor, after 8 days of cultu
re. As demonstrated by Northern analysis, VT at the levels between 50
and 100 ng/ml superinduced IL-2, 4, 5, and 6 mRNAs in PMA-stimulated E
L-4 cells during a 24 hr culture period. Similar effects in PMA-treate
d samples were observed for CHX at 50, 100, 250, 1000, and 10000 ng/ml
. mRNA levels for both IL-4 and IL-5, but not IL-2 and IL-6, were incr
eased in unstimulated EL-4 cultures exposed to 50 and 100 ng/ml VT for
48 hr when analyzed by reverse transcriptase-polymerase chain reactio
n. Using [H-3]leucine incorporation as a measurement of protein synthe
sis, IC(50)s for VT and CHX were estimated to be 280 and 55 ng/ml, res
pectively. This study indicates that VT as well as CHX could increase
production of several interleukins in the EL-4 model even when present
at concentrations that partially inhibited protein synthesis, whereas
IL mRNA superinduction occurred across a broader range of concentrati
ons that included maximal protein synthesis inhibition. (C) 1994 Acade
mic Press, Inc.