Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elafin, a human skin derived inhibitor of human leukocyte elastase, was tested for inhibitory activity against proteinase 3, an elastin degrading proteinase of neutrophils. The inhibitory activity of elafin was compared with antileukoprotease and eglin C. Elafin proved to be a potent inhibitor of elastin-FITC degradation showing an IC 50 of 9.5 x 10(-9) M. Potency was found to be more than 100-fold higher as compared with antileukoprotease and eglin C.
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PMID:Elafin is a potent inhibitor of proteinase 3. 198 20

Polymorphonuclear leukocytes contain well-defined proteolytic enzymes in their azurophilic granules that can be released into tissues during inflammation, producing a localized excess of proteases that causes a protease-antiprotease imbalance with subsequent tissue destruction. The antiproteolytic compounds of the epidermis, such as the protease inhibitors elafin and antileukoprotease, are thought to counteract the proteolytic tissue damage. We investigated the urine of patients suffering from inflammatory skin conditions (e.g., erysipelas, psoriasis) for the presence of urinary antiprotease activities. Purification of elastase-inhibitory activities from pooled urine samples by cation exchange high-performance liquid chromatography and preparative and analytical reverse-phase high-performance liquid chromatography yielded two different types of inhibitors. One was a cationic, acid-stable, and elastase-specific inhibitor of M(r) 6,000 by size-exclusion high-performance liquid chromatography. N-terminal amino acid sequence analysis of the first 28 residues showed identity with elafin, an elastase-specific inhibitor recently isolated from psoriatic scales. The second anti-protease activity was due to two forms of urinary bikunin, the inhibitory subunit of inter-alpha-inhibitor. Both bikunin fragments, with M(r) 4,000 and 16,000, were identified by N-terminal amino acid sequence analysis of the first 10 residues and were characterized by an antiproteolytic profile against human leukocyte elastase, cathepsin G, and trypsin. Urinary protease inhibitors may serve as diagnostic markers of inflammatory diseases.
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PMID:Antiprotease activity in urine of patients with inflammatory skin disorders. 756 Nov 59

Secretory leukocyte protease inhibitor (SLPI) and elafin are structurally similar, low-molecular-weight antiproteases produced in the lung. We have developed a simple method for distinguishing the antiprotease activities of SLPI and elafin in lung lavage fluid from those of alpha 1-antitrypsin (alpha 1-AT) that is based on the resistance of the low-molecular-weight antiproteases to inactivation by cetyltrimethylammonium bromide. In a study of 23 healthy, nonsmoking volunteers, we found that the low-molecular-weight antiproteases accounted for 22 +/- 2% (mean +/- SEM, n = 23) of the total neutrophil elastase-inhibitory capacity of human bronchoalveolar lavage fluid (BALF). Elafin activity was below the limit of detection. SLPI activity (as measured by inhibition of alpha-chymotrypsin) accounted for 72 +/- 4% (mean +/- SEM, n = 23) of the low-molecular-weight antiprotease activity in BALF. Measurements of SLPI in the lavage fluid samples by enzyme-linked immunosorbent assay (ELISA) agreed closely with values obtained by measuring the activity of this inhibitor. The activity of the low-molecular-weight antiproteases decreased significantly (p < 0.05), from 9.0 +/- 0.8 to 7.0 +/- 0.6 pmol of neutrophil elastase inhibited per mL (mean +/- SEM, n = 23), following acute ozone exposure.
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PMID:Contribution of secretory leukocyte proteinase inhibitor to the antiprotease defense system of the peripheral lung: effect of ozone-induced acute inflammation. 758

Measurements of the intracellular free calcium concentration [Ca2+]i in single cells of the human tracheal gland cell line MM 39 demonstrate dynamic changes in [Ca2+]i after their exposure to human neutrophil elastase (HNE). A heterogeneity in [Ca2+]i responses measured cell to cell in monolayer culture is evident: cells generate an initial [Ca2+]i peak rise with or without a delayed time (up to 180 sec) followed either by a rapid return to baseline, asynchronous oscillations or a sustained plateau phase. From basal concentration of 85 +/- 15 nM, HNE (1 microM) produces a [Ca2+]i increase of 91 +/- 66 nM in about 50% of responding cells. At lower concentrations of HNE (0.1 microM, 0.01 microM), the [Ca2+]i rise remains similar, but only 30-40% of the cells are responding. Pretreatment of cells with the recombinant elafin protein, a specific elastase inhibitor, reduces both the [Ca2+]i response to HNE and the number of responding cells. Electron microscopy observations reveal an increased number of secretory granules located beneath the cell plasma membrane after HNE treatment. These results suggest that intracellular [Ca2+]i changes may be associated to the HNE-induced exocytosis in human tracheal gland cells. These findings could have implications with regard to the pathogenesis of increased mucus secretion in human airway diseases.
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PMID:Asynchronous dynamic changes of intracellular free Ca2+ and possible exocytosis in human tracheal gland cells induced by neutrophil elastase. 762 43

Elafin is an elastase inhibitor with a unique structure, not related to the serpin family, which includes the neutrophil elastase inhibitor. The gene was identified in this laboratory by subtractive hybridization between RNAs from human mammary tumor-derived cells and cDNAs from normal human mammary epithelial cells. Elafin is consistently expressed in normal mammary epithelial cells, but is down-regulated in most breast tumor cell lines. Restriction fragment analysis detected no gross deletions or rearrangement of the gene in any of the tumor cell lines examined. The elafin gene was cloned, and both the cDNA and the promoter region were sequenced. A major positive upstream promoter element was identified by chloramphenicol acetyltransferase assay and deletion analysis, active in normal cell extracts but not in extracts of tumor cells. These results demonstrate that differential expression of elafin in normal mammary epithelial cells and breast tumor cells is regulated at the transcriptional level. Cell synchronization experiments demonstrated that elafin mRNA is down-regulated in S phase in normal cells. These results suggest that elafin may act as an inhibitor of cell cycle progression.
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PMID:Differential expression of elafin in human normal mammary epithelial cells and carcinomas is regulated at the transcriptional level. 778 Sep 65

The epidermal serine proteinase inhibitor SKALP (also known as elafin), directed against human leukocyte elastase and proteinase 3, is strongly induced in suprabasal keratinocytes during inflammation. The presence of SKALP/elafin in urine has been demonstrated for several inflammatory skin disorders, such as psoriasis, erythroderma, and erysipelas. In this study we investigated whether SKALP/elafin levels in serum and urine of psoriatic patients can be used as a marker for disease activity during treatment. Patients with severe chronic disabling psoriasis were treated for 16 weeks with cyclosporin A, which resulted in a marked clinical improvement as measured with the PASI score. SKALP/elafin levels both in serum and urine were determined with an enzyme-linked immunosorbent assay (ELISA). Measurements were performed at the start of the cyclosporin A treatment, and after regular intervals up to 16 weeks. The results indicate that 1) SKALP/elafin determination in serum rather than in urine is the preferred method, because the decrease in serum SKALP levels during therapy is more pronounced and correlated better with the clinical course of the patients; 2) SKALP/elafin levels in serum decreased during cyclosporin A treatment (p < 0.05); and 3) SKALP/elafin levels in serum correlate with the PASI score (p < 0.01). We conclude that SKALP/elafin measurement in serum of patients with severe psoriasis provides a tool for monitoring disease activity.
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PMID:Levels of skin-derived antileukoproteinase (SKALP)/elafin in serum correlate with disease activity during treatment of severe psoriasis with cyclosporin A. 782 74

This study investigated the effect of neutrophil depletion and neutrophil elastase inhibition on the severity of skeletal muscle reperfusion injury. In a rodent model, indices (experimental/normal limb) of gastrocnemius muscle viability (histochemical staining), oedema (wet:dry weight ratio) and myeloperoxidase content (neutrophil recruitment) were assessed in normal (no ischaemia), ischaemic (6-h unilateral hindlimb ischaemia), control (6-h ischaemia and 4-h reperfusion), neutrophil-depleted rats (given antineutrophil serum) and rats receiving the neutrophil elastase inhibitor Elafin. Neutrophil recruitment muscle infarction and oedema did not occur in normal limbs, or in those subjected to ischaemia without reperfusion. In contrast increased muscle myeloperoxidase levels (P < 0.001), muscle infarction (P < 0.01) and oedema (P < 0.001) all occurred in the reperfused limbs of control animals compared with those of normal and ischaemic rats. Antineutrophil serum and Elafin both reduced neutrophil recruitment during reperfusion (P < 0.001 and P < 0.01 respectively) and muscle viability was preserved. Reperfusion oedema still occurred however, suggesting that altered endothelial permeability is mediated by factors other than neutrophils.
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PMID:Role of neutrophil depletion and elastase inhibition in modifying skeletal muscle reperfusion injury. 785 93

Skin-derived antileukoproteinase (SKALP), also known as elafin, is a strong and specific inhibitor of elastase and proteinase 3. SKALP is not present in normal epidermis, but is expressed by epidermal keratinocytes under hyperproliferative conditions such as psoriasis, wound healing, and in cell culture. In human epidermal tumours, SKALP is differentially expressed and restricted to tumours with distinct squamous differentiation. We have studied the presence of both SKALP and one of its known target enzymes, leukocyte elastase, in 41 squamous cell carcinomas of the skin. SKALP expression correlated with the degree of differentiation: strong expression was seen in well-differentiated cells and expression was absent in poorly differentiated tumour cells. Most of the squamous cell carcinomas showed elastase-positive cells in the tumour stroma and also within the tumour cell nests. SKALP may interfere with the proteolytic activity of infiltrating inflammatory cells or with hitherto unknown proteinases from the tumour cells. We hypothesize that in squamous cell carcinoma progressive loss of SKALP expression could facilitate tumour spread.
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PMID:Demonstration of skin-derived antileukoproteinase (SKALP) and its target enzyme human leukocyte elastase in squamous cell carcinoma. 796 7

The expression of mRNA for elafin/SKALP, an inhibitor of leukocyte elastase and proteinase 3, in human normal and psoriatic epidermis was examined by in situ hybridization. In normal epidermis, elafin/SKALP mRNA was detected in the granular layer, but not in the spinous or basal layers. In fully developed psoriatic lesions, elafin/SKALP mRNA was found in the suprabasal layers of the ridges, and in the upper two thirds of the stratum malpighii at the elongated rete ridges. Intense staining was noted near the subcorneal microabscess in psoriasis vulgaris and under the subcorneal pustule in localized pustular psoriasis. In the marginal psoriatic epidermis, elafin/SKALP mRNA was expressed from the middle or upper spinous layer to the subcorneal layer, and the cells expressing elafin/SKALP mRNA increased especially under the parakeratotic corneal layer intermingled with pyknotic nuclei of neutrophils. These findings suggest that the induction of elafin/SKALP gene expression is related closely to the infiltration of neutrophils into the epidermis in psoriasis and plays an important role in protecting the skin components against the tissue damage caused by the infiltrated leukocytes.
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PMID:Up-regulation of elafin/SKALP gene expression in psoriatic epidermis. 802 86

Elafin and antileukoprotease are potent peptide-like inhibitors of human leukocyte elastase and have been isolated from human skin and bronchial mucus. Elafin proved to be a potent inhibitor of proteinase 3, whereas other inhibitors of human leukocyte elastase such as antileukoprotease and eglin C proved to be much less effective.
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PMID:Inhibition of proteinase 3 activity by peptides derived from human epidermis. 829 75


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