Expression of SKALP/elafin during wound healing in human skin

Abstract

Skin-derived antileukoproteinase (SKALP), Key words SKALP • Wound healing • also known as elafin, is a proteinase inhibitor with Antileukoproteinase • Elastase specificity for polymorphonuclear leucocyte (PMN)-derived elastase and proteinase-3. SKALP is absent in normal human epidermis, but is strongly induced in Introduction inflammatory dermatoses such as psoriasis. SKALP is putatively involved in the regulation of cutaneous in-Proteinase activity is regulated systemically by numerous flammation by inhibiting PMN derived proteinases. plasma-derived inhibitors, such as a!-proteinase inhibitor The aim of this study was to investigate SKALP ex-and a 2-macroglobulin. However, in normal human epipression and PMN infiltration during wound healing dermis only low levels of antiproteinase activity directed in human skin. This was examined in healing exci-against the major polymorphonuclear leucocyte (PMN)-sional wounds in normal skin and in impaired healing derived proteinases (e.g. elastase, proteinase-3 and cathepin various types of chronic venous ulcers. Tissues were sin G) can be detected. Antiproteinase activity is upreguanalysed using immunohistocliemistry and Northern lated in inflammatory skin diseases such as psoriasis [5, blot analysis. Healing of excisional wounds was stud-18-20] and epidermal tumours [2]. In previous studies we ied from day 0 to day 14. An influx of PMN was seen and others have characterized this antiproteinase activity rapidly after wounding and was maximal between day and found it to be an inducible inhibitor of elastase and 2 and 4 and then subsided. SKALP was induced within proteinase 3 [23]. This inhibitor has been named skin-de-48 h and was expressed in the suprabasal keratino-rived antileukoproteinase (SKALP) [18], also known as cytes of the wound edge and the migrating epidermal elafin [23,24] or elastase-specific inhibitor (ESI) [15 |. sheet. SKALP expression was maximal on day 4 and Cloning of the SKALP cDNA and gene has revealed that was downregulated at the time of complete reepithe-the molecule contains several N-terminal transglutamilialization (7-14 days). In venous ulcers, PMN were nase substrate motifs, in addition to the antiproteinase doabundant in the wound bed and scarce under the main that was already known [11,12,14]. SKALP is a sewound edge. SKALP was strongly expressed in the creted molecule, and we have recently demonstrated its keratinocytes of the wound edge in all types of ulcers presence in urine and plasma of psoriatic patients [1,4]. studied. In the wound bed, SKALP was not detectable. Our results suggest that S SKALP may be involved in the regulation of euta-P plays a role in the neous animation by inhibiting PMN-derived o acute, inflammatory phase of wound healing. From teinases. However, no direct evidence for its function in the kinetics and topology of SKALP expression we vivo is available at present. Previous investigations have surmise that it negatively regulates PMN infiltration.

SLPI and elafin: one glove, many fingers

“…For example, elafin seems to be important in the cellular differentiation of foetal to adult submandibular glands [124], and its degree of expression is related to the degree of differentiation in lung carcinomas [125,126]. Meanwhile, SLPI and elafin expression have been noted in response to cutaneous injury in humans [46,127], and SLPI has been shown to be an important endogenous factor in both cutaneous and oral mucosal wound healing [128][129][130]. Moreover, in the search for mechanisms delineating dermal scarring from oral scar-free healing, SLPI has been suggested as an active mediator.…”

Hypertrophic scarring is associated with epidermal abnormalities: an immunohistochemical study

“…[1][2][3] Skin injury has profound effects on keratinocyte differentiation, as shown by the induction of the hyperproliferation-associated cytokeratins 6 and 16. 4,5 Many other changes in gene expression patterns in the epidermis during wound healing have been described, including up-regulation of SKALP/elafin, 6 changes in integrin expression, 7-10 and alteration of cytokine profiles. 10,11 Changes in keratinocyte proliferation have been documented in a number of studies.…”

Epidermal Elafin Expression Is an Indicator of Poor Prognosis in Cutaneous Graft-versus-Host Disease

“…In contrast to normal skin where it is not detectable (Pfundt et al, 1996;Kamsteeg et al, 2010), elafin is abundantly secreted in diverse skin conditions exhibiting hyperproliferative features. These include psoriasis (Kamsteeg et al, 2010), wound healing (van Bergen et al, 1996), diverse skin neoplasms (Alkemade et al, 1993), and lichen planus (unpublished data from our lab). Our study not only revealed increased elafin expression in clGVHD, another disease characterized by keratinocytic hyperproliferation (Shulman et al, 2006), but also demonstrated a strong association between high elafin expression and epidermal thickening.…”