Phosphatidylserine-specific receptor contributes to TGF-beta production in macrophages through a MAP kinase, ERK.
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.
Otsuka
Masaki
M
School of Pharmacy Tokyo University of Pharmacy and Life Science, Tokyo, Japan.
Goto
Kentaro
K
Tsuchiya
Seishi
S
Aramaki
Yukihiko
Y
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D015153:Blotting, Western; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D010718:Phosphatidylserines / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D019138:Antibodies, Blocking; D004791:Enzyme Inhibitors; D008081:Liposomes; D010718:Phosphatidylserines; C498708:Ptdsr protein, mouse; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; C408123:phosphatidylserine receptor; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases