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Dual Role of Ceramide in the Control of Apoptosis Following IL-2 Withdrawal¹

Ignacio Flores^*, Carlos Martinez-A^*, Yusuf A. Hannun and Isabel Mérida^2,*

^* Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid, Spain; and Departments of Medicine and Cell Biology, Duke University Medical Center, Durham NC 27710

Ceramide is largely known as a lipid second messenger with pleiotropic effects. Increases in ceramide levels have been related to the onset of apoptosis, terminal differentiation, or growth suppression. In this study, addition of exogenous C₂-ceramide to CTLL-2 cells is found to block IL-2-induced cell cycle entry, as well as the apoptosis triggered by IL-2 deprivation. The protective effect of C₂-ceramide is achieved only in the early stages following cytokine deprivation and is related to the inhibition of bcl-x_L degradation and the induction of a G₀ arrest of cells. The same treatment over a longer time when, as we demonstrate, ceramide is produced physiologically, enhances cell death by apoptosis. The dual effect of ceramide both in protecting from or inducing apoptosis is discussed further.

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