Regulatory role of ceramide in interleukin (IL)-1Β-induced E-selectin expression in human umbilical vein endothelial cells: Ceramide enhances IL-1Β action, but is not sufficient for E-selectin expression

Atsushi Masamune, Yasuyuki Igarashi, Sen Itiroh Hakomori

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

Recent studies indicate that sphingolipids mediate several cellular processes. We assessed roles of sphingolipids in the regulation of E-selectin expression in human umbilical vein endothelial cells. All exogenously-added sphingolipids (sphingosine, C2-ceramide, sphingosine 1-phosphate, and N,N-dimethylsphingosine) failed to induce E-selectin expression by themselves. C2-ceramide at 5 μM enhanced interleukin-1Β (IL-1Β)-induced E-selectin expression 2.7-fold, whereas other sphingolipids tested had no effects on this process. Sphingomyelinase, but not phospholipascs A2, C, or D, mimicked the enhancing effect of C2-ceramide. Northern blot analyses revealed that C2-ceramide and sphingomyelinase increased interleukin-1Β-induced E-selectin gene transcription levels. C2-ceramide and sphingomyelinase induced NF-κB activation by themselves and enhanced activation by IL-1Β, which is essential for E-selectin expression. Immunological analyses with anti-NF-κB antibodies showed that subunit composition of NF-κ Bactivated by IL-1Β differs from that activated by C2-ceramide, suggesting that signaling pathways utilized by these stimuli may be different. Treatment with C2-ceramide or sphingomyelinase did not alter NF-ELAM1 specific binding activity. IL-1Β induced sphingomyelin hydrolysis to ceramide; intracellular ceramide level increased to 182% of control value at 30 min. Taken together, these findings suggest that (i) sphingomyelin hydrolysis to ceramide does not trigger, but rather enhances cytokine-induced E-selectin expression, in part through NF-κB; (ii) sphingomyelin hydrolysis to ceramide does not mediate all the effects of IL-1Β, although it may play important roles in IL-1Β signal transduction in human umbilical vein endothelial cells.

Original languageEnglish
Pages (from-to)9368-9375
Number of pages8
JournalJournal of Biological Chemistry
Volume271
Issue number16
DOIs
Publication statusPublished - 1996 Apr 19

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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