Abstract
The concentration of extracellular calcium appears critical to the initiation of keratinocyte differentiation. Prostaglandins (PGs) have also been implicated in cell differentiation. Consequently, the participation of endogenous eicosanoids in calcium-induced differentiation of human keratinocytes was evaluated in vitro. Our results demonstrate that: (1) exogenously introduced PGE 2, the major keratinocyte-derived eicosanoid, but not prostaglandin I 2 (PGI 2) or its stable metabolite 6-keto-PGF 1α, enhances calcium-induced cornified envelope formation, an established marker of keratinocyte differentiation; (2) increasing extracellular calcium increased endogenous PGE 2 synthesis by cultured keratinocytes; (3) blocking endogenous PGE 2 synthesis with indomethacin significantly suppresses calcium-induced formation of the cornified envelope; and (4) adding back PGE 2 to indomethacin-treated keratinocytes is able to re-establish the control level of cornified envelope formation following stimulation by calcium. These data document the participation of endogenously generated PGE 2 in the modulation of calcium-induced differentiation by human keratinocytes.
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