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.

The Serine Protease Marapsin Is Expressed in Stratified Squamous Epithelia and Is Up-regulated in the Hyperproliferative Epidermis of Psoriasis and Regenerating Wounds

“…Elafin is a potent inhibitor of human neutrophil elastase and of proteinase-3 and has antimicrobial and anti-inflammatory activities, which contribute to tissue protection against inflammation and neutrophil elastase activity (30,31). Similar to marapsin, elafin is constitutively expressed in the suprabasal keratinocyte layers of stratified squamous epithelia except for skin, where it is induced under hyperproliferative conditions (24,25,32). Notably, it is also transiently up-regulated during cutaneous wound healing and down-regulated when reepithelialization is completed.…”

“…Notably, it is also transiently up-regulated during cutaneous wound healing and down-regulated when reepithelialization is completed. Like marapsin, elafin expression is localized to the suprabasal keratinocytes at the migrating wound edge (32). Therefore, it is possible that marapsin is involved in related biological processes, such as in antimicrobial defense.…”

Antimicrobial peptides and pregnancy

“…AMPs are produced in response to cutaneous injury (vanBergen et al 1996, Wingens et al 1998, and AMP knockout mice show impaired cutaneous wound healing and increased inflammation and elastase activity (Ashcroft et al 2000, Angelov et al 2004. AMPs present at the site of wound repair may also be protecting the wound from potential infection, with HBD1-3 shown to be present in human wound fluid (Frohm et al 1996).…”

“…Deficiencies can result in loss of function of AMPs resulting in increased susceptibility to infection and inflammation, which play a role in many diseases (Beisswenger & Bals 2005). They are likely to have important functions in the female reproductive tract, where infection and inflammation can jeopardize successful pregnancy.…”

Arterial Elastase Activity After Balloon Angioplasty and Effects of Elafin, an Elastase Inhibitor

“…27 It has been suggested that elafin plays a role in downregulating the inflammatory response in tissues commonly exposed to pathogens. 28 Elafin has now been used successfully to prevent or reverse a number of cardiovascular disease states in which serine elastases have been shown to be involved in the pathogenesis, including myocarditis, 8,12 transplant coronary arteriopathy, 11 and vein graft degeneration. 14 The addition of the present finding of the effects of elafin in our model suggests that elafin may also be a useful therapeutic approach for conditions in which intimal hyperplasia plays a significant role, such as atrioventricular shunt stenosis and in-stent restenosis.…”