Sphingomyelinase but not ceramide induces nitric oxide synthase expression in rat brain microglia.

Microglia, brain inflammatory cells, are activated in injured brain and function similar to macrophages. The activated microglia produce nitric oxide (NO), a major toxic substance from these cells, by inducing expression of inducible NO synthase (iNOS). In this study, we found that sphingomyelinase (SMase) alone induced NO release/iNOS mRNA expression in cultured rat brain microglia. On the contrary to SMase, however, membrane-permeable c2-ceramide had little effect on NO release/iNOS mRNA expression. Fumonisin B1, an inhibitor of de novo synthesis of ceramide, did not reduce lipopolysaccharide (LPS)-induced NO release. However, neither SMase nor c2-ceramide enhanced LPS- or Abeta (25-35)-induced NO release/iNOS mRNA expression.