A Comparison of the Effects of Lipopolysaccharide and Ceramide on Arachidonic Acid Metabolism in THP-1 Monocytic Cells

Ceramide has been shown to be an important second messenger for signal transduction in cells of myeloid lineage. Studies have suggested that lipopolysaccharide (LPS) may activate signaling pathways by mimicking the action of ceramide. We explored this hypothesis with THP-1 cells in terms of the effects of LPS, C2 ceramide, and sphingomyelinase on arachidonic acid metabolism as measured by the release of radiolabeled eicosanoids. Arachidonic acid metabolism was activated by both LPS and ceramide. However, the ratio of prostaglandin E2to leukotriene C4was 10 times higher in cells treated with LPS than with ceramide. Unlike LPS, prior exposure to ceramide did not desensitize the cells to subsequent challenge with either LPS or ceramide, nor could LPS desensitize the cells to challenge with ceramide. The results suggest that, although LPS and ceramide may share signaling components, the signaling pathways are not identical.