Nuclear factor-κB inhibitors alleviate nivalenol-induced cytotoxicity in HL60 cells

Tricothecene mycotoxins, such as nivalenol, are toxic to leukocytes. To elucidate the molecular mechanism of nivalenol toxicity, we investigated the involvement of nuclear factor-kappa B (NF-kappa B) in nivalenol-induced cytotoxicity in HL60 cells using the NF-kappa B inhibitors pyrrolidinedithiocarbamate (PDTC) and dexamethasone. Cells were treated with the chemicals for 24 h before assays were performed. Nivalenol elicited interleukin (IL)-8 secretion. IL-8 secretion was lower in cells concomitantly treated with nivalenol and NF-kappa B inhibitors than with nivalenol alone. Nivalenol reduced monocyte chemotactic protein (MCP)-1 secretion. MCP-1 secretion was higher in cells concomitantly treated with nivalenol and NF-kappa B inhibitors than with nivalenol alone. NF-kappa B inhibitors thus alleviated the effects of nivalenol, indicating that NF-kappa B is important for nivalenol-caused changes in cytokine secretion. Nivalenol hindered cell proliferation, and dexamethasone reduced this effect, suggesting that NF-kappa B contributes to cell proliferation. Thus, it appears that NF-kappa B is involved in nivalenol-induced toxicity in HL60 cells. (C) 2010 Elsevier B.V. All rights reserved.