title: Stimulatory effect of fibroblast-derived prostaglandin E₂ on keratinocyte stratification in the skin equivalent.
abstract: Epidermal-dermal interaction plays important roles in physiological events such as wound healing. In this study, we examined a double paracrine mechanism between keratinocytes and fibroblasts through interleukin-1 (IL-1) and an IL-1-induced inflammatory mediator prostaglandin E₂ (PGE₂) using the skin equivalent. The epidermal layer of the skin equivalent expressed high levels of IL-1α mRNA (IL1A mRNA) and relatively low levels of IL-1β mRNA (IL1B mRNA). IL1A mRNA was not detected in fibroblasts. Fibroblasts also expressed low but not negligible levels of IL1B mRNA only in the presence of keratinocytes. Expression of prostaglandin-endoperoxide synthase 2 mRNA (PTGS2 mRNA) and production of PGE₂ in three-dimensionally cultured fibroblasts were noticeably stimulated by co-culture with keratinocytes, whereas PTGS2 mRNA expression in the epidermal layer was very low. In addition, hydroxyprostaglandin dehydrogenase 15-(NAD) mRNA was highly expressed in keratinocytes but not in fibroblasts, and exogenous IL-1β stimulated PTGS2 mRNA expression in the dermal equivalent. The thickness of the epidermal layer and the number of MKI67-positive keratinocytes in the skin equivalent were decreased by treatment with indomethacin, and the decrease recovered when exogenous PGE₂ was added. These results indicate that keratinocytes stimulate their own proliferation through a double paracrine mechanism mediated by IL-1 and PGE₂.
authors.affiliation: Scleroprotein Research Institute, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
authors.forename: Koji Y
authors.initials: KY
authors.lastname: Arai
authors.forename: Atsuko
authors.initials: A
authors.lastname: Fujioka
authors.forename: Ryoko
authors.initials: R
authors.lastname: Okamura
authors.forename: Toshio
authors.initials: T
authors.lastname: Nishiyama
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D004817:Epidermis / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014945:Wound Healing
chemical_list: D012333:RNA, Messenger; D015232:Dinoprostone