Involvement of p38 MAP Kinase in the Inhibitory Effects of Phosphatidylserine Liposomes on Nitric Oxide Production from Macrophages Stimulated with LPS

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-κB, 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.