Divergent role of ceramide generated by exogenous sphingomyelinases on NF-κB activation and apoptosis in human colon HT-29 cells

This study examined the role of ceramide generated by exogenous sphingomyelinases (SMases) on transcription nuclear factor-kappaB (NF-kappaB) activation and apoptosis in human colon epithelial HT-29 cells. Exogenous neutral (N) and acidic (A) SMase activated NF-kappaB with different kinetics, accounting for the diverse pattern of DNA binding of NF-kappaB complexes activated by tumor necrosis factor-alpha (TNF). NSMase activated predominantly RelA/p52 and RelA/p50 dimers within 30 min, while ASMase activated the p50/p50 homodimer by 20 h. The predominant activation of RelA-containing kappaB complexes by TNF or NSMase paralleled the induction of interleukin-8. HT-29 cells were sensitive to ASMase and TNF but resistant to NSMase. However, the apoptotic potential of NSMase was masked by NF-kappaB, as its prior inactivation sensitized HT-29 cells to NSMase. Thus, the generation of ceramide by exogenous SMases participates differentially in inflammation and apoptosis. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.