Geldanamycin, an Inhibitor of Heat Shock Protein 90, Mitigates Nivalenol-caused Changes in Cytokine Secretion in HL60 Cells
ISSN | 00213551 |
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NII recode ID (NCID) | AA0068709X |
To elucidate the molecular mechanism underlying the toxicity of nivalenol, we investigated the involvement of heat shock protein 90 (Hsp90), a molecular chaperone, in nivalenol-induced cytotoxicity in human promyelocytic leukemia HL60 cells using an Hsp90-specific inhibitor geldanamycin. Cytokine levels and cell proliferation were investigated after 24-h treatment. Nivalenol significantly elicited interleukin-8 (IL-8) secretion, conversely, geldanamycin faintly altered. IL-8 secretion in cells co-treated with these chemicals was much lower than that with nivalenol alone, indicating the importance of Hsp90 for nivalenol-induced IL-8 secretion. Both nivalenol and geldanamycin alone reduced monocyte chemotactic protein-1 (MCP-1) secretion. Regardless of geldanamycin, the values in the nivalenol-treated samples were almost the same. If Hsp90 is indifferent to the nivalenol signal transduction, the effects of these chemicals should be additive. However, statistical analysis shows that these effects are not additive, indicating that geldanamycin mitigates nivalenol’s effect on MCP-1 secretion. While nivalenol markedly hindered proliferation, geldanamycin retarded it moderately. The value of cells co-treated with these chemicals was lower than that with nivalenol alone, meaning that geldanamycin does not protect against nivalenol-caused retardation of proliferation. In this study, we showed that Hsp90 is involved in nivalenol-associated changes in cytokine secretion, however, it is unclear whether Hsp90 is involved in the nivalenol-caused retardation of proliferation.
Date of issued | |
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Creator | NAGASHIMA Hitoshi NAKAGAWA Hiroyuki KUSHIRO Masayo |
Subject |
interleukin-8 monocyte chemotactic protein-1 |
Publisher | Japan International Research Center for Agricultural Sciences |
Available Online | |
NII resource type vocabulary | Journal Article |
Volume | 45 |
Issue | 4 |
spage | 441 |
epage | 444 |
DOI | 10.6090/jarq.45.441 |
Rights | Japan International Research Center for Agricultural Sciences |
Language | eng |