PGE_2 exerts its effect on the LPS-induced release of TNF-alpha, ET-1,IL-lalpha,IL-6 and IL-10 via the EP2 and EP4 receptor in rat liver macrophages

摘要

Lipopolysaccharide (LPS) induces a release of tumor necrosis factor (TNF)-alpha, endothelin (ET)-l, interleukin (IL)-lalpha, IL-6 and IL-10 in rat liver macrophages (Kupffer cells). Prostaglandin (PG)E_2 inhibits the release of the fibrogenic mediators TNF-a, ET-1 and IL-la, and enhances the release of the anti-fibrogenic mediators IL-6 and IL-10. This effect of PGE_2 is mimicked by specific agonists for the PGE_2 receptors EP2 and EP4;whereas,agonists for the PGE_2 receptors EP1 and EP3 are inactive.Rat liver macrophages express mRNA encoding the PGE_2 receptors EP2 and EP4 but not the PGE2 receptors EP1 and EP3.These data suggest that PGE_2 exerts its anti-fibrogenic effect through the EP2 and EP4 receptor by inhibiting the release of the fibrogenic mediators TNF-alpha, ET-1 and IL-lalpha,and by enhancing the release of the anti-fibrogenic mediators IL-6 and IL-10 in liver macrophages.