ENDOGENOUS PROSTAGLANDIN-E(2) MODULATES CALCIUM-INDUCED DIFFERENTIATION IN HUMAN SKIN KERATINOCYTES

The concentration of extracellular calcium appears critical to the ini tiation of keratinocyte differentiation. Prostaglandins (PGs) have als o been implicated in cell differentiation. Consequently, the participa tion of endogenous eicosanoids in calcium-induced differentiation of h uman keratinocytes was evaluated in vitro. Our results demonstrate tha t: (1) exogenously introduced PGE2, the major keratinocyte-derived eic osanoid, but not prostaglandin I2 (PGI2) or its stable metabolite 6-ke to-PGF1alpha, enhances calcium-induced cornified envelope formation, a n established marker of keratinocyte differentiation; (2) increasing e xtracellular calcium increased endogenous PGE2 synthesis by cultured k eratinocytes, (3) blocking endogenous PGE2 synthesis with indomethacin significantly suppresses calcium-induced formation of the cornified e nvelope; and (4) adding back PGE2 to indomethacin-treated keratinocyte s is able to re-establish the control level of cornified envelope form ation following stimulation by calcium. These data document the partic ipation of endogenously generated PGE2 in the modulation of calcium-in duced differentiation by human keratinocytes.