Involvement of phosphatidylinositol-3-kinase and ERK pathways in the production of TGF-beta1 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-beta1 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-beta1. 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-beta1. Furthermore, PS-liposomes activated macrophages to induce TGF-beta1 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-beta1 which regulates macrophage functions.
Otsuka
Masaki
M
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Negishi
Yoichi
Y
Aramaki
Yukihiko
Y
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008081:Liposomes / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010718:Phosphatidylserines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000906:Antibodies; D002867:Chromones; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D008081:Liposomes; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D010718:Phosphatidylserines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011956:Receptors, Cell Surface; D053773:Transforming Growth Factor beta1; C408123:phosphatidylserine receptor; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one