title: Characterization and differentiation-dependent regulation of secreted phospholipases A in human keratinocytes and in healthy and psoriatic human skin.
abstract: Secreted phospholipases A2 (sPLA2) expressed in the skin are thought to be involved in epidermal barrier homeostasis as well as in inflammation. We investigated the expression of the novel sPLA2 subtypes in human skin at mRNA and protein levels in the epidermis and primary keratinocytes from healthy human skin, and in skin sections from patients with psoriasis, where the integrity of the epidermis is drastically affected. Immunofluorescence studies using specific antibodies for the different sPLA2 enzymes show that sPLA2-IB, -IIF, and -X are predominantly expressed in suprabasal layers, whereas sPLA2-V and -IID are detected in the basal and spinous layers. sPLA2-IIA is weakly expressed, and sPLA2-IIE and XIIA are not detectable. Accordingly, in differentiated human primary keratinocyte cultures, the expression of sPLA2-IB, -IIF and -X was increased, whereas that of sPLA2-V and -IID was markedly decreased. In psoriatic skin, sPLA2-X was dramatically downregulated in the epidermis, whereas increased amounts of this enzyme together with sPLA2-IIA, -IID, and -IB appeared in the dermis. An enhanced release of these enzymes with the exception of sPLA2-IID was also observed after treatment of HaCaT keratinocytes with tumor necrosis factor-alpha/interferon-gamma. Treatment of HaCaT cells with sPLA2-X and -IB resulted in an increase in prostaglandin E2 formation, suggesting a proinflammatory role of these enzymes during psoriasis. sPLA2-V completely disappeared. The differential locations of the sPLA2 enzymes propose distinct roles of individual enzymes in skin.
authors.affiliation: pharmazentrum frankfurt, University Hospital, Frankfurt/Main, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Haas
authors.forename: Maurizio
authors.initials: M
authors.lastname: Podda
authors.forename: Martin
authors.initials: M
authors.lastname: Behne
authors.forename: Silvia
authors.initials: S
authors.lastname: Gurrieri
authors.forename: Angel
authors.initials: A
authors.lastname: Alonso
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fürstenberger
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
authors.forename: Gérard
authors.initials: G
authors.lastname: Lambeau
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.forename: Marietta
authors.initials: M
authors.lastname: Kaszkin
mesh_terms: D001706:Biopsy; D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D010741:Phospholipases A; D002118:Calcium