Dissociation of endogenous cellular ceramide from NF-κB activation

Jonathan C. Betts, Adam B. Agranoff, Gary J. Nabel, James A. Shayman

Research output: Contribution to journalArticlepeer-review

Abstract

The participation of cell ceramide in tumor necrosis factor (TNF)-α- stimulated NF-κB activation in Jurkat T cells and HL-60 cells was studied. TNF-α readily stimulated NF-κB activity in both cell lines as assayed by electrophoretic mobility shift assay and the use of a human immunodeficiency virus-chloramphenicol acetyltransferase reporter construct. However, TNF-α stimulation did not increase cell ceramide levels in either cell line. The exogenous addition of a short chain ceramide, N-acetylsphingosine, to Jurkat cells had no effect on NF-κB activity. When Jurkat T cells were exposed to the glucosylceramide synthase inhibitor, 1-phenyl-2-decanoylamino-3- morpholino-1-propanol, endogenous ceramide levels increased 4-fold. The increase in ceramide, however, did not result in NF-κB activation nor did it potentiate TNF-α or phorbol ester-stimulated activity. We conclude that TNF- α-induced NF-κB activation occurs in Jurkat and HL-60 cell lines that do not demonstrate an increase in TNF-α-induced ceramide. Increasing ceramide levels by the addition of short chain ceramides or the use of a glucosylceramide synthase inhibitor can be dissociated from activation of NF- κB by TNF-α.

Original languageEnglish (US)
Pages (from-to)8455-8458
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number11
StatePublished - Mar 18 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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