title: Endogenous prostaglandin E2 modulates calcium-induced differentiation in human skin keratinocytes.
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 PGE2, the major keratinocyte-derived eicosanoid, but not prostaglandin I2 (PGI2) or its stable metabolite 6-keto-PGF1 alpha, enhances calcium-induced cornified envelope formation, an established marker of keratinocyte differentiation; (2) increasing extracellular calcium increased endogenous PGE2 synthesis by cultured keratinocytes; (3) blocking endogenous PGE2 synthesis with indomethacin significantly suppresses calcium-induced formation of the cornified envelope; and (4) adding back PGE2 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 PGE2 in the modulation of calcium-induced differentiation by human keratinocytes.
authors.affiliation: Department of Dermatology, University of California, San Francisco.
authors.forename: C B
authors.initials: CB
authors.lastname: Evans
authors.forename: S
authors.initials: S
authors.lastname: Pillai
authors.forename: M E
authors.initials: ME
authors.lastname: Goldyne
mesh_terms: D002118:Calcium / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D012867:Skin / Q000166:cytology
chemical_list: D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin