Involvement of p38 MAP Kinase in the inhibitory effects of phosphatidylserine liposomes on nitric oxide production from macrophages stimulated with LPS

Abstract

The mechanism by which liposomes composed of phosphatidylserine (PS-liposomes) inhibit nitric oxide (NO) production was investigated in vitro using mouse peritoneal macrophages stimulated with LPS. The expression of inducible NO synthase (i-NOS) mRNA was completely inhibited by PS-liposomes. PS-liposomes inhibited tyrosine phosphorylation of p38 MAP kinase, which is required for the activation of p38 MAP kinase. NO production was also inhibited by SB203580, a specific inhibitor of p38 MAP kinase. However, there was no effect on the activation of transcription factor NF-kappaB, a primary transcription factor involved in induction of i-NOS. These results suggested that PS-liposomes inhibit NO production up stream of the transcription of i-NOS mRNA, and that the inhibition of p38 MAP kinase is crucial for this effect.