Negatively charged liposomes inhibit tyrosine phosphorylation of 41-kDa protein in murine macrophages stimulated with LPS.
Examination was made of the mechanism of the inhibitory effects of liposomes on NO production using thioglycollate-induced mouse peritoneal macrophages stimulated by LPS. NO production was inhibited dose dependently by negatively charged liposomes containing phosphatidylserine (PS-liposomes) but not neutral liposomes composed with phosphatidylcholine. To clarify this mechanism, the effect of liposomes on protein tyrosine phosphorylation was investigated by Western blot analysis, and tyrosine phosphorylation of protein with 41 kDa was inhibited by PS-liposomes dose dependently. NO production and tyrosine phosphorylation of p41 were also inhibited by herbimycin A, a tyrosine kinase inhibitor. TNF-alpha production was also inhibited by PS-liposomes. The inhibition of tyrosine phosphorylation of protein with 41 kDa by PS-liposomes may thus lead to the suppression on NO and TNF-alpha productions from macrophages stimulated by LPS.
Aramaki
Y
Y
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Matsuno
R
R
Nitta
F
F
Arima
H
H
Tsuchiya
S
S
D000818:Animals; D016227:Benzoquinones; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides / Q000494:pharmacology; D008081:Liposomes / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008970:Molecular Weight; D009569:Nitric Oxide / Q000096:biosynthesis; D010718:Phosphatidylserines / Q000737:chemistry; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides; D008081:Liposomes; D010718:Phosphatidylserines; D011809:Quinones; D014409:Tumor Necrosis Factor-alpha; D017828:Rifabutin; D019000:Phosphotyrosine; D009569:Nitric Oxide; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases