Rubratoxin B induced the secretion of hepatic injury-related colony stimulating factors in human hepatoma cells.
The induction of cytokine secretion by rubratoxin B was investigated using human hepatoma cell lines HepG2 and HuH-7. Interleukin (IL)-8, macrophage colony stimulating factor (M-CSF) and granulocyte-macrophage (GM)-CSF were detected in the media of rubratoxin B-treated both cell lines, and their levels peaked at about 40 microg/ml. Rubratoxin B-induced cytokine secretion was enhanced by tumor necrosis factor (TNF)-alpha in HepG2 cells. While emodin increased GM-CSF secretion, the secretion of the others was decreased, indicating that they are regulated differently in rubratoxin B-treated HepG2 cells. To our knowledge, this is the first report that an exogenous stimulus induced the secretion of M-CSF and GM-CSF in hepatocyte-derived hepatoma cells, suggesting that rubratoxin B is an excellent model compound to study the mechanisms of M-CSF and GM-CSF secretion. Our results showed that hepatotoxin rubratoxin B has a potential to induce the secretion of these two CSFs, implying that these factors play roles in rubratoxin B-caused hepatic injury.
Nagashima
Hitoshi
H
National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan. nagasima@nfri.affrc.go.jp
Nakamura
Kumiko
K
Goto
Tetsuhisa
T
D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D004642:Emodin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D009183:Mycotoxins / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D016209:Interleukin-8; D009183:Mycotoxins; C100297:rubratoxins; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004642:Emodin