Indomethacin inhibition of cell proliferation induced by the phorbolester TPA is reversed by prostaglandin E2 in mouse epidermis in vivo

The proliferative response of mouse epidermis to the phorbolester TPA (10 nmoles) in vivo is completely inhibited by a single topical application of indomethacin one hour before TPA. DNA labeling in normal mouse epidermis is not significantly depressed by the drug. The inhibition can be reversed by applying prostaglandin E₂ (>3 nmoles) simultaneously with TPA, whereas prostaglandin F_2α (100 nmoles) is ineffective. The indomethacin-sensitive event is restricted to the first hour after phorbol ester treatment. TPA-induced skin inflammation is not influenced by the drug. It is proposed that prostaglandin E₂, or a closely related compound, mediates the mitogenic effect of TPA in mouse skin.