Mycotoxins nivalenol and deoxynivalenol differentially modulate cytokine mRNA expression in Jurkat T cells.
Deoxynivalenol (DON) and its hydroxylated form nivalenol (NIV) are Fusarium mycotoxins that occur in cereal grains alone or in combination. Several studies have shown that these metabolites affect lymphocyte functions. However, the molecular mechanisms underlying their activities are still partially known. To address this issue, we examined the influence of NIV and DON in modulating IFNgamma, IL-2 and IL-8 mRNA levels in Jurkat T cells. In PMA/ionomycin stimulated cells, pre-incubated with increasing concentrations of NIV, transcription was induced in the range 0.06-2 microM; higher concentrations of NIV were found non-stimulating (4 microM) or inhibitory (8 microM) for IFNgamma and IL-2 whereas IL-8 was still induced. DON administration elicited a similar profile for IL-8 and IFNgamma, whilst IL-2 mRNA was induced in a broader range of concentrations. Combination of NIV and DON at 1:1 and 1:10 ratios essentially restored the cytokine transcriptional pattern observed with NIV alone but the level of transcripts, with the exception of IL-8, peaked at lower concentrations suggesting interactive effects. Moreover both mycotoxins caused inhibition of cell proliferation, mediated by induction of apoptosis, confirming previous results and highlighting the usefulness of Jurkat as a T-cell model to study the effects of mycotoxins on the immune functions in humans.
Severino
Lorella
L
Department of Pathology and Animal Health, Division of Toxicology, University of Naples Federico II, via Delpino 1, 80137 Naples, Italy.
Luongo
Diomira
D
Bergamo
Paolo
P
Lucisano
Antonia
A
Rossi
Mauro
M
D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D009183:Mycotoxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014255:Trichothecenes / Q000494:pharmacology*
D016207:Cytokines; D009183:Mycotoxins; D012333:RNA, Messenger; D014255:Trichothecenes; C038405:nivalenol; C007262:deoxynivalenol