title: Nuclear factor-κB inhibitors alleviate nivalenol-induced cytotoxicity in HL60 cells.
abstract: Tricothecene mycotoxins, such as nivalenol, are toxic to leukocytes. To elucidate the molecular mechanism of nivalenol toxicity, we investigated the involvement of nuclear factor-κB (NF-κB) in nivalenol-induced cytotoxicity in HL60 cells using the NF-κB inhibitors pyrrolidinedithiocarbamate (PDTC) and dexamethasone. Cells were treated with the chemicals for 24h before assays were performed. Nivalenol elicited interleukin (IL)-8 secretion. IL-8 secretion was lower in cells concomitantly treated with nivalenol and NF-κB 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-κB inhibitors than with nivalenol alone. NF-κB inhibitors thus alleviated the effects of nivalenol, indicating that NF-κB is important for nivalenol-caused changes in cytokine secretion. Nivalenol hindered cell proliferation, and dexamethasone reduced this effect, suggesting that NF-κB contributes to cell proliferation. Thus, it appears that NF-κB is involved in nivalenol-induced toxicity in HL60 cells.
authors.affiliation: National Food Research Institute, National Agriculture and Food Research Organization, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan. nagasima@affrc.go.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagashima
authors.forename: Masayo
authors.initials: M
authors.lastname: Kushiro
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakagawa
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D009183:Mycotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014255:Trichothecenes / Q000037:antagonists & inhibitors* / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D016209:Interleukin-8; D009183:Mycotoxins; D016328:NF-kappa B; D013859:Thiocarbamates; D014255:Trichothecenes; C066229:prolinedithiocarbamate; C038405:nivalenol; D003907:Dexamethasone; D011392:Proline