LOCALIZATION OF PROSTAGLANDIN-H SYNTHASE-1 AND SYNTHASE-2 IN MOUSE SKIN - IMPLICATIONS FOR CUTANEOUS FUNCTION

Prostaglandin-H synthase (PGHS)-1 and -2 expression in mouse skin and in keratinocytes in culture was determined using immunohistochemistry and Western blot analysis. In normal skin PGHS-1 immunoreactivity was found in individual keratinocytes present in the interfollicular epide rmis and the upper part of the hair follicle. PGHS-2 immunostaining wa s detected in very few individual basal cells of the interfollicular e pidermis and of the hair follicle. Upon induction by TPA of an inflamm atory epidermal hyperplasia (regenerative hyperplasia) the number of P GHS-2-expressing keratinocytes scattered throughout the basal but not the suprabasal compartment of the interfollicular epidermis was found to be increased while PGHS-1 expression remained unchanged. PGHS-2 imm unoreactivity in paraffin sections from TPA-treated skin showed a nucl ear in some and a perinuclear and cytoplasmic localization in other ke ratinocytes, This different distribution may correlate with the prolif erative state, since immunofluorescence analysis of mouse keratinocyte s in culture demonstrated a predominant perinuclear and cytoplasmic PG HS-2 localization in cycling keratinocytes but a prevalent staining of the nucleus and the nuclear membrane in noncycling cells. Stimulation of proliferation of murine primary keratinocytes by serum resulted in an increased PGHS-2 expression, whereas induction of terminal differe ntiation by Ca2+ caused a down-regulation of PGHS-2 protein. Only mino r changes in PGHS-1 expression were seen. Owl data suggest that expres sion of PGHS-2 in mouse skin epidermis is related to epithelial regene ration. (C) 1998 Academic Press.