Abstract
Studying apoptosis induced by T cell receptor (TCR) cross-linking in the T cell hybridoma, 3DO, we found both neutral sphingomyelinase activation and production of ceramide upon receptor engagement. Pharmacological inhibition of ceramide production by the fungal toxin, fumonisin B1, impaired TCR- induced interleukin (IL)-2 production and programmed cell death. Addition of either exogenous ceramide or bacterial sphingomyelinase reconstituted both responses. Moreover, specific inactivation of neutral sphingomyelinase by antisense RNA inhibited IL-2 production and mitogen-activated protein kinase activation after TCR triggering. These results suggest that ceramide production by activation of neutral sphingomyelinase is an essential component of the TCR signaling machinery.
Original language | English (US) |
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Pages (from-to) | 1581-1589 |
Number of pages | 9 |
Journal | Journal of Experimental Medicine |
Volume | 189 |
Issue number | 10 |
DOIs | |
State | Published - May 17 1999 |
Externally published | Yes |
Keywords
- Activation
- Apoptosis
- Ceramide
- Neutral sphingomyelinase
- Signaling
- T cell receptor
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology