A role for neutral sphingomyelinase-mediated ceramide production in T cell receptor-induced apoptosis and mitogen-activated protein kinase-mediated signal transduction

Laura Tonnetti, Maria Concetta Verí, Ezio Bonvini, Luciano D'Adamio

Research output: Contribution to journalArticle

81 Scopus citations


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 languageEnglish (US)
Pages (from-to)1581-1589
Number of pages9
JournalJournal of Experimental Medicine
Issue number10
StatePublished - May 17 1999



  • Activation
  • Apoptosis
  • Ceramide
  • Neutral sphingomyelinase
  • Signaling
  • T cell receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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