LPS-mediated septic shock is augmented in ceramide synthase 2 null mice due to elevated activity of TNFα-converting enzyme

FEBS Lett. 2015 Aug 4;589(17):2213-7. doi: 10.1016/j.febslet.2015.06.045. Epub 2015 Jul 13.


Tumor necrosis factor α (TNFα) is an inflammatory cytokine that plays an intimate role in septic shock. Injection of high levels of lipopolysaccharide induces septic shock and death in mice within 30 h, whereas ceramide synthase 2 (CerS2) null mice, defective in the synthesis of very-long acyl chain ceramides, die within ∼10 h. The augmented rate of death of CerS2 null mice is due to elevated levels of TNFα secretion as a result of enhanced activity of TNFα-converting enzyme (TACE). We discuss the relationship between the sphingolipid acyl chain length and TACE activity and the relevance of this data to septic shock.

Keywords: Ceramide; Ceramide synthase 2; LPS-mediated sepsis; Sphingolipid; Tumor necrosis factor α; Tumor necrosis factor α converting enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / metabolism*
  • ADAM17 Protein
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Ceramides / metabolism
  • Gene Expression
  • Hepatocytes / metabolism
  • Lipopolysaccharides
  • Macrophages / metabolism
  • Mice, Knockout
  • Microscopy, Confocal
  • Reverse Transcriptase Polymerase Chain Reaction
  • Shock, Septic / chemically induced
  • Shock, Septic / metabolism*
  • Sphingolipids / metabolism
  • Sphingosine N-Acyltransferase / genetics
  • Sphingosine N-Acyltransferase / metabolism*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*


  • Ceramides
  • Lipopolysaccharides
  • Sphingolipids
  • Tumor Necrosis Factor-alpha
  • Cers2 protein, mouse
  • Sphingosine N-Acyltransferase
  • ADAM Proteins
  • ADAM17 Protein
  • Adam17 protein, mouse