Involvement of phosphatidylinositol-3-kinase and ERK pathways in the production of TGF-β1 by macrophages treated with liposomes composed of phosphatidylserine

We explored the involvement of phosphatidylinositol 3-kinase (PI3K) and ERK pathways in the production of TGF-β1 by macrophages treated with liposomes composed of phosphatidylserine (PS-liposomes). PS-liposomes activated Akt, downstream of the PI3K signal cascade, and ERK which led to the expression of TGF-β1. PI3K inhibitors, LY294002 and wortmannin, inhibited the activation of Akt and ERK following the treatment with PS-liposomes. These inhibitors also suppressed the production of TGF-β1. Furthermore, PS-liposomes activated macrophages to induce TGF-β1 expression through PS-specific receptors. These findings suggested that a PI3K-ERK signaling pathway via the PS-receptor is intimately involved in the production of TGF-β1 which regulates macrophage functions.