Sphingomyelinase but not ceramide induces nitric oxide synthase expressionin rat brain microglia

Microglia, brain inflammatory cells, are activated in injured brain and fun ction similar to macrophages. The activated microglia produce nitric oxide (NO), a major toxic substance from these cells, by inducing expression of i nducible 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-cerami de had little effect on NO release/iNOS mRNA expression. Fumonisin B1, an i nhibitor of de novo synthesis of ceramide, did not reduce lipopolysaccharid e (LPS)-induced NO release. However, neither SMase nor c2-ceramide enhanced LPS- or A beta (25-35)-induced NO release/iNOS mRNA expression. (C) 2001 E lsevier Science Ireland Ltd. All rights reserved.