12-O-Tetradecanoylphorbol-13-acetate and the induction of prostaglandin E2 generation by human keratinocytes: a re-evaluation

Abstract

12-O-Tetradecanoylphorbol-13-acetate (TPA) induces prostaglandin E₂ (PGE₂ synthesis in mouse keratinocytes and is associated with the induction of keratinocyte proliferation as well as accelerated differentiation. In human keratinocytes, TPA has been reported not to induce the release of either ³H-labeled arachidonic acid or ³H-labeled prostaglandins, even though cell differentiation is stimulated. Because PGE₂ has been associated with the modulation of cell differentiation and because of technical problems inherent in evaluating arachidonic acid metabolism using only radlolabeled substrates, we evaluated the ability of TPA to induce endogenous PGE₂ generation by cultured human keratinocytes using a specific and sensitive enzyme immunoassay. With this technique, TPA was found to induce a dose-dependent (1.6×10⁻¹²−1.6×10⁻⁸ M) increase in PGE₂ generation. These results are consistent with observations made not only in mouse keratinocytes but in other mammalian and human cell types. Documenting the ability of TPA to stimulate PGE₂ production in human keratinocytes is very relevant to current theories regarding the role of PGE₂ In keratinocyte differentiation as well as to establishing parallels between the murine and human skin models.