Abstract
We explored the involvement of the phosphatidylserine (PS)-receptor in the production of TGF-beta by macrophages treated with PS-liposomes. The binding of anti-PS-receptor antibody to macrophages was specifically inhibited by PS-liposomes. The antibody led to an increase in the production of TGF-beta, and also activated ERK, a member of the MAP kinase. But no activations in p38 and JNK were observed. ERK inhibitor, U0126 completely prevented TGF-beta production. On the addition of a TGF-beta neutralizing antibody or U0126, the inhibitory effect of the anti-PS-receptor antibody on macrophage function, nitric oxide production, was restored. These findings suggested that TGF-beta is one of factors produced by PS-liposomes, and the ERK signaling pathway via the PS-receptor is intimately involved in the production of TGF-beta in macrophages.
MeSH terms
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Animals
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Antibodies, Blocking / pharmacology
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Blotting, Western
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Flow Cytometry
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Liposomes
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Macrophages / drug effects
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Macrophages / enzymology
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Macrophages / metabolism*
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Male
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Mice
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Mice, Inbred C3H
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism*
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Nitric Oxide / biosynthesis
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Phosphatidylserines / pharmacology*
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / drug effects*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Transforming Growth Factor beta / biosynthesis*
Substances
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Antibodies, Blocking
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Enzyme Inhibitors
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Liposomes
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Phosphatidylserines
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Ptdsr protein, mouse
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Receptors, Cell Surface
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Transforming Growth Factor beta
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phosphatidylserine receptor
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Nitric Oxide
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Mitogen-Activated Protein Kinases