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-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.
Aramaki
Y
Y
Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. aramaki@ps.toyaku.ac.jp
Matsuno
R
R
Tsuchiya
S
S
D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008081:Liposomes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism / Q000494:pharmacology; D010718:Phosphatidylserines / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D008081:Liposomes; D016328:NF-kappa B; D009573:Nitrites; D010718:Phosphatidylserines; D011725:Pyridines; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580