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Title: EFFECTS OF SPHINGOLIPID-DERIVED PRODUCTS AND FUMONISINS ON THE CYTOKINE-INDUCED IL-8 PRODUCTION IN A HUMAN ASTROCYTOMA CELL LINE

Author
item KIKUCHI, YUTAKA - FRA, 3620-30-00
item Richard, John

Submitted to: Toxic Microorganisms Symposium Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 11/18/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: To clarify the effect of the mycotoxins, fumonisins, as inhibitors of ceramide synthesis, on the inflammatory reactions in central nervous system, we compared the effects of sphingosine, C2-ceramide, and fumonisin B1 on cytokine-induced IL-8 production in a human astrocytoma cell line, U373MG cells. As previously reported, U373MG cells produced high levels of IL-8 in response to IL-1 and TNF-alpha. In addition, both IL-1 (1 pM) and TNF-alpha (1 nM) synergistically induced IL-8 production. Sphingosine (10 uM) further enhanced the IL-1/TNF-induced response. C2-ceramide (10 uM) and fumonisin B1 (10 uM) synergistically enhanced the IL-1/TNF-induced response. Sphingosine or fumonisin B1, but not C2-ceramide, enhanced IL-1- induced response. On the other hand, C2-ceramide enhanced the TNF- induced response. Without cytokine stimulation, these sphingosine analogs induced the IL-8 production, but the induced IL-8 levels were very low. Apparently both sphingosine and ceramide are required for the maximal IL-8 production, and fumonisin B1 acts to increase the intracellular sphingosine level by inhibiting sphinganine (sphingosine) N-acyltransferase activity. In addition, it is likely that fumonisin B1 also inhibits the degradation of sphingosine.