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.