Induction of cytokine secretion by rubratoxin B was investigated using HL60 cells. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 were secreted from 40 and 80 microg/ml rubratoxin B-treated cells. In 20 and 40 microg/ml rubratoxin B-treated samples, monocyte chemotactic protein (MCP)-1 was released. These rubratoxin B-induced cytokines are known to promote liver myelocytic cell infiltration, and activate cytokine-recruited cells. As a result, recruited myelocytic cells are considered to contribute to hepatic injury. We investigated the effects of tyrosine kinase inhibitors genistein and emodin. Genistein reduced the release of all three cytokines from rubratoxin B-treated cells. Likewise, emodin diminished the secretion of MCP-1. Alternatively, emodin reversed on the secretion of TNF-alpha, and the release of IL-8 was not affected. Since emodin did not impede rubratoxin B-caused TNF-alpha and IL-8 secretion, they appeared to be regulated differently from MCP-1 secretion, suggesting that rubratoxin B exerts its toxicity using two or more signal transduction pathways.