Skin-derived antileucoproteases (SKALPs): characterization of two new elastase inhibitors from psoriatic epidermis

Schalkwijk, Joost; Chang, A.; Janssen, Pauline; Jongh, G. J. De; Mier, P.D.

doi:10.1111/j.1365-2133.1990.tb07285.x

Cited by 101 publications

(79 citation statements)

References 22 publications

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“…It has been proved that SKALP/elafin inhibits the activities of at least three serine proteinases derived from polymorphonuclear leucocytes (PMN), such as human leucocyte elastase, porcine pancreatic elastase and human leucocyte proteinase 3 (Schalkwijk et al, 1990(Schalkwijk et al, , 1991Wiedow et al, 1991). The secretion of SKALP/ elafin from cultured human keratinocytes has been found .…”

Section: Discussionmentioning

confidence: 99%

“…The method of the isolation and purification of SKALP/elafin both from psoriatic scales and from cultured human keratinocytes has been described previously (Schalkwijk et al, 1990(Schalkwijk et al, , 1991. In brief, psoriatic scales were homogenized in distilled water, yielding a suspension that was boiled and centrifuged, followed by chloroform extraction and centrifugation.…”

Section: Materials and Methods Isolation And Purification Of Skalp/elmentioning

confidence: 99%

“…Also several kinds of specific inhibitors of such proteases have been shown to inhibit cancer invasion and metastasis (Baker et al, 1990;Cajot et al, 1990;Albini et al, 1991;Declerck et al, 1992;Kennedy, 1994;Kobayashi et al, 1994Kobayashi et al, , 1995. Hence, the protease inhibitors could be considered to possess the potential to be a useful tool for the development of a new therapeutic method against cancer.Recently, a new inducible elastase inhibitor, SKALP (skinderived antileucoproteinase) has been isolated from psoriatic skin (Schalkwijk et al, 1990. SKALP has been shown to be a heat-stable, cationic protein with an apparent molecular weight of 9-11 kDa.…”

mentioning

confidence: 99%

“…Recently, a new inducible elastase inhibitor, SKALP (skinderived antileucoproteinase) has been isolated from psoriatic skin (Schalkwijk et al, 1990. SKALP has been shown to be a heat-stable, cationic protein with an apparent molecular weight of 9-11 kDa.…”

mentioning

confidence: 99%

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Immunohistochemical expression of SKALP/elafin in squamous cell carcinoma of the oesophagus

Yamamoto

Egami²,

Kurizaki³

et al. 1997

Br J Cancer

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Summary In this study, the immunohistochemical expression of a new inducible elastase inhibitor, SKALP (skin-derived antileucoproteinase)/elafin, in the tissue of squamous cell carcinoma and uninvolved oesophageal mucosa was studied using a polyclonal rabbit anti-serum against SKALP/elafin. The results were compared with the immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and the TUNEL assay in serial sections. In non-malignant oesophageal mucosa, the expression of SKALP/elafin was localized in the cells of the stratified zone overlying the PCNA-positive basal zone. In oesophageal cancer, the incidence of the expression was significantly related to the degree of the differentiation of the tumour. Characteristically, the expression was almost limited in tumour cell nests that had a clear squamous phenotype. In tumour cell nests, the expression of SKALP/elafin was localized in the cells overlying PCNA-expressing cells and no expression was found in the cells that expressed PCNA; DNA fragmentation was often observed in the same cell layers as those in which SKALP/elafin immunoreactivity was found. This enzyme inhibitor is speculated to be involved in the induction of the cell differentiation and apoptosis of human squamous cell carcinoma cells of the oesophagus.Keywords: SKALP/elafin; oesophageal cancer; immunohistochemistry Squamous cell carcinoma (SCC) is the major histological type of oesophageal cancer in Japan, being one of the most lethal neoplasms of the digestive organs. At present, only limited numbers of patients can be cured by conventional therapy, such as surgical resection, irradiation and chemotherapy, one reason being that oesophageal cancer has an extremely high potential for invasion into the surrounding organs and for metastasis. Several proteases produced by the cancer cell itself have been reported to be associated with cancer invasion and metastasis (Liotta et al, 1980(Liotta et al, , 1986Wooley, 1984;Nakajima et al, 1987;Reich et al, 1988;Basset et al, 1990). Also several kinds of specific inhibitors of such proteases have been shown to inhibit cancer invasion and metastasis (Baker et al, 1990;Cajot et al, 1990;Albini et al, 1991;Declerck et al, 1992;Kennedy, 1994;Kobayashi et al, 1994Kobayashi et al, , 1995. Hence, the protease inhibitors could be considered to possess the potential to be a useful tool for the development of a new therapeutic method against cancer.Recently, a new inducible elastase inhibitor, SKALP (skinderived antileucoproteinase) has been isolated from psoriatic skin (Schalkwijk et al, 1990. SKALP has been shown to be a heat-stable, cationic protein with an apparent molecular weight of 9-11 kDa. DNA of SKALP has been cloned and sequenced (Schalkwijk et al, 1991) and has proved to be identical to elafin, which is a similar epidermal protease inhibitor described by Wiedow et al (1990). The expression of SKALP/elafin has not been found in the cells of normal epidermis but is found in differentiating cells of psoriasis and wound healing (Schalkwijk et...

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Section: Discussionmentioning

confidence: 99%

Section: Materials and Methods Isolation And Purification Of Skalp/elmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Immunohistochemical expression of SKALP/elafin in squamous cell carcinoma of the oesophagus

Yamamoto

Egami²,

Kurizaki³

et al. 1997

Br J Cancer

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“…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.…”

mentioning

confidence: 99%

Expression of SKALP/elafin during wound healing in human skin

et al. 1996

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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.

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Induction of normal and psoriatic phenotypes in submerged keratinocyte cultures

et al. 1996

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Lesional psoriatic epidermis displays a number of phenotypic changes that are distinct from the differentiation program found in normal interfollicular epidermis. In psoriatic epidermis, keratinocytes are hyperproliferative and several differentiation-associated molecules are expressed that are absent in normal skin (e.g., cytokeratins (CK) 6, 16, and 17, and the epidermal proteinase inhibitor SKALP/ elafin). In addition, several molecules which are normally restricted to the stratum granulosum are strongly upregulated in the stratum spinosum (e.g., psoriasis-associated fatty acid binding protein (PA-FABP), psoriasin, involucrin, and transglutaminase). The aim of this study was to develop in vitro culture systems which (a) would allow to study the induction of normal and psoriatic differentiation pathways, and (b) would be amenable for screening of antipsoriatic drugs. Here we have investigated several models for induction of differentiation with respect to the expression of markers for the normal and psoriatic phenotype. Cell cycle parameters and expression levels of CK1, CK10, CK16, SKALP/elafin, transglutaminase, involucrin, psoriasin, and PA-FABP were assessed in these models using flow cytometry, immunocytochemistry, and Northern blot analysis. We observed that induction of differentiation with fetal calf serum resembled the psoriatic phenotype (sustained hyperproliferation; high levels of CK16, SKALP/elafin, transglutaminase, and involucrin; moderate psoriasin expression), whereas differentiation induced by growth factor depletion in a confluent culture resembled the normal differentiation phenotype (low proliferative rate; high expression levels of CK1 and CK10; moderate expression of involucrin and transglutaminase; low expression levels of SKALP/elafin and CK16; absence of psoriasin). We propose that these models can be used to study expression and pharmacological modulation of selected differentiation genes and the coordinated expression of sets of genes associated with epidermal differentiation programs.

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Skin-derived antileucoproteases (SKALPs): characterization of two new elastase inhibitors from psoriatic epidermis

Cited by 101 publications

References 22 publications

Immunohistochemical expression of SKALP/elafin in squamous cell carcinoma of the oesophagus

Immunohistochemical expression of SKALP/elafin in squamous cell carcinoma of the oesophagus

Expression of SKALP/elafin during wound healing in human skin

Induction of normal and psoriatic phenotypes in submerged keratinocyte cultures

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