Abstract
Lipopolysaccharide (LPS) induces a release of tumor necrosis factor (TNF)-α, endothelin (ET)-1, interleukin (IL)-lα, IL-6 and IL-10 in rat liver macrophages (Kupffer cells). Prostaglandin (PG)E 2 inhibits the release of the fibrogenic mediators TNF-α, ET-1 and IL-lα, 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 PGE 2 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-α, ET-1 and IL-lα, and by enhancing the release of the anti-fibrogenic mediators IL-6 and IL-10 in liver macrophages.
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