Geldanamycin, an Inhibitor of Heat Shock Protein 90, Mitigates Nivalenol-caused Changes in Cytokine Secretion in HL60 Cells

JARQ : Japan Agricultural Research Quarterly
ISSN 00213551
書誌レコードID(総合目録DB) AA0068709X
45-04-11.pdf63.7 KB

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.

作成者 NAGASHIMA Hitoshi NAKAGAWA Hiroyuki KUSHIRO Masayo


monocyte chemotactic protein-1

公開者 Japan International Research Center for Agricultural Sciences
国立情報学研究所メタデータ主題語彙集(資源タイプ) Journal Article
開始ページ 441
終了ページ 444
DOI 10.6090/jarq.45.441
権利 Japan International Research Center for Agricultural Sciences
言語 eng