Fumonisin B1-induced alterations in cytokine expression and apoptosis signaling genes in mouse liver and kidney after an acute exposure

Fumonisin B-1 (FB1), a carcinogenic mycotoxin produced primarily by fungus Fusarium verticillioides in corn, causes several fatal animal diseases. In mice, liver is the primary site of its toxicity. Our previous Study showed that maximum induction of interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) was observed at 4 and 8 h, respectively, after an acute po FB1 treatment. To further investigate the time-related induction of other cytokines and genes involved in apoptosis signaling, male BALB/c mice were administered orally with either saline or 25 mg/kg of FB1 and sampled 4 or 8 h after treatment. Expression of various genes was analyzed by ribonuclease protection assay. FB1 treatment caused increased expression of TNFalpha and interleukin (IL)-1beta in both liver and kidney, whereas IL-1alpha and IL-1 receptor antagonist (IL-1Ra) expression was induced only in the liver. Expression of TNFalpha, signaling molecules, TNF receptor 55 and receptor interacting protein, was increased in liver and kidney after FB1 treatment. Caspase 8 expression was increased only in liver with no changes in kidney with FB1. FB1 treatment induced expression of Fas in liver and kidney with no alterations in Fas signaling molecules, Fas ligand, Fas-associated death domain and Fas-associated protein factor. Treatment of mice with FB1 increased the expression of B-Myc, c-Myc and Max, oncogenic transcription factors in the kidney. FB1 toxicity caused induction of cytokine network in liver with involvement of TNFalpha signaling pathway. Increased expression of caspase 8 involved in the TNFalpha signaling pathway may contribute to the apoptosis, whereas IL-1Ra induction could contribute to the proliferating effects observed in FBI toxicity. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.