The role of neutral sphingomyelinase produced ceramide in lipopolysaccharide‐mediated expression of inducible nitric oxide synthase

• DOI: 10.1046/j.1471-4159.2003.02165.x
• Publication Date: 2005-07-28T21:33:56Z
• Authors: Je‐Seong Won; Yeong‐Bin Im; Mushfiquddin Khan; Avtar K. Singh; Inderjit Singh
• Keywords: Ceramide synthase; Sphingomyelin phosphodiesterase; Sphingolipid

Abstract Lipopolysaccharide (LPS) and interferon‐γ (IFN) treatment of C6 rat glioma cells increased the intracellular ceramide level expression inducible nitric oxide synthase ( iNOS ) gene. To delineate possible role in induction , we examined source associated signal transduction pathway(s) with use inhibitors generation. The inhibitor neutral sphingomyelinase (3‐ O ‐methylsphingomyelin, MSM) inhibited whereas acidic (SR33557) or that de novo synthesis (fumonisin B1) had no effect on . MSM‐mediated inhibition was reversed by supplementation exogenous C 8 ‐ceramide, suggesting production (nSMase) is a key mediator gene correlated decrease activity ras. Inhibition co‐transfected promoter dominant negative ras supported nSMase‐dependent regulation NF‐κB DNA binding its transactivity were also reduced MSM pretreatment, completely ‐ceramide. As transactivity, activation may be downstream Our results suggest generated nSMase critical via ras‐mediated under inflammatory conditions.