12-O-TETRADECANOYLPHORBOL-13-ACETATE AND THE INDUCTION OF PROSTAGLANDIN E(2) GENERATION BY HUMAN KERATINOCYTES - A REEVALUATION

12-O-Tetradecanoylphorbol-13-acetate (TPA) induces prostaglandin E(2) (PGE(2)) synthesis in mouse keratinocytes and is associated with the i nduction of keratinocyte proliferation as well as accelerated differen tiation. In human keratinocytes, TPA has been reported not to induce t he release of either H-3-labeled arachidonic acid or H-3-labeled prost aglandins, even though cell differentiation is stimulated. Because PGE (2) has been associated with the modulation of cell differentiation an d because of technical problems inherent in evaluating arachidonic aci d metabolism using only radiolabeled substrates, we evaluated the abil ity of TPA to induce endogenous PGE(2) generation by cultured human ke ratinocytes using a specific and sensitive enzyme immunoassay. With th is technique, TPA was found to induce a dose-dependent (1.6x10(-2)-1.6 x10(-8) M) increase in PGE(2) generation. These results are consistent with observations made not only in mouse keratinocytes but in other m ammalian and human cell types. Documenting the ability of TPA to stimu late PGE(2) production in human keratinocytes is very relevant to curr ent theories regarding the role of PGE(2) in keratinocyte differentiat ion as well as to establishing parallels between the murine and human skin models.