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

Tumor necrosis factor alpha (TNF alpha) 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 similar to 10 h. The augmented rate of death of CerS2 null mice is due to elevated levels of TNF alpha secretion as a result of enhanced activity of TNF alpha-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. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.