Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteolytic enzymes may be involved in blister formation in dermatitis herpetiformis (DH). We have examined collagenase, gelatinase and elastase-like enzyme activities in fluids collected from spontaneous blisters and from suction blisters raised on developing DH-lesions induced by application of potassium iodide. Control suction blisters were raised on unaffected DH-skin and on healthy volunteers. High enzyme activities were found in spontaneous blisters, and suction blister fluids obtained from developing lesions showed increased levels of gelatinase and elastase-like enzymes. Inhibitor studies revealed that a part of the elastase-like enzyme activity might be derived from inflammatory cells. Gel filtration chromatography disclosed two separate elastase-like enzymes which, as they had high molecular weights, could be either enzyme-inhibitor complexes or aggregates.
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PMID:Proteolytic enzymes in blister fluids from patients with dermatitis herpetiformis. 300 37

We have investigated potential mechanisms for blister formation by assaying proteolytic enzymes in the blister fluids of patients with various bullous diseases. Blister fluids were obtained from patients with dermatitis herpetiformis (DH), bullous pemphigoid (BP), chronic bullous disease of childhood (CBDC), and pemphigus vulgaris (PV). The cells were recovered by centrifugation, and the supernatants as well as the cell pellets were assayed first for collagenase activity using [3H]proline-labeled type I collagen as substrate. Collagenase activity could be detected in most cases with DH, BP, and CBDC, while no activity was found in 2 cases of PV or in 5 control blister fluids obtained from suction blisters induced in healthy control subjects. Elastase activity was assayed in the same blister fluids by using a synthetic substrate succinyl-(L-alanyl)3-paranitroanilide or soluble [14C]valine-labeled tropoelastin. High levels of elastase activity were present in all DH patients, while lower, but clearly detectable, levels were found in BP, CBDC, and PV. The enzyme activity in BP was inhibited by Na2EDTA, but not by phenylmethylsulfonyl fluoride (PMSF), and Ca2+ stimulated the activity, suggesting that the enzyme in BP was a metalloproteinase. In cell-free supernatants of the DH blister fluids, the elastase activity was markedly decreased by PMSF, indicating that most of the enzyme activity was due to a serine protease. The cells recovered from DH blister fluids also contained high levels of elastase activity which could be inhibited by PMSF but not by Na2EDTA. Thus, in DH, the elastase activity is probably derived from polymorphonuclear leukocytes abundantly present in the lesions. The results indicate that active proteases are present in the blister fluids of skin diseases, and they may play a mechanistic role in the blister formation by degrading connective tissue components of the dermis and the dermal-epidermal junction.
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PMID:Demonstration of collagenase and elastase activities in the blister fluids from bullous skin diseases. Comparison between dermatitis herpetiformis and bullous pemphigoid. 630 88

A technique has been devised to isolate the thin papillary part of the dermis from punch biopsies. Papillary dermis has been treated with various proteolytic enzymes in order to release or solubilize the granular IgA deposits from the papillary dermis of patients with dermatitis herpetiformis. Incubation of the thin skin preparations with pepsin caused a disappearance of the specific fluorescence with antibodies to human IgA. After peptic digestion small amounts of IgA could be detected in the supernatants. There was some evidence that this amount was larger for preparations from patients with dermatitis herpetiformis than from controls. Corresponding procedures with trypsin, collagenase, or elastase had no detectable effect on the IgA deposits. The experiments with elastase seemed to give support for previous reports on association between the granular IgA deposits and the microfibrils of elastic fibers.
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PMID:Dermatitis herpetiformis: preparation of papillary dermis and the effect of proteolytic enzymes on the IgA deposits. 639 32

Because dermatitis herpetiformis is characterized by neutrophilic inflammation and destructive changes in the basement membrane zone, we studied the in situ expression of interstitial collagenase and stromelysin-1 in 11 lesions. A prominent signal for collagenase mRNA was consistently detected in the basal keratinocytes of rete ridges surrounding the neutrophilic abscesses in 10 of 11 lesions, and the expression was independent of the age of the lesion and the migratory state of the basal keratinocytes. Expression of stromelysin-1 was detected in seven of 11 lesions and co-localized with collagenase. No expression of the 92-kDa gelatinase mRNA or matrilysin protein was found in the vicinity of neutrophilic accumulations or the damaged basement membrane. Urokinase-type plasminogen activator mRNA was found in basal keratinocytes in seven of nine samples. Collagenase, stromelysin-1, and urokinase-type plasminogen activator were not expressed in normal-appearing skin of patients with dermatitis herpetiformis. Our results suggest that in lesions of dermatitis herpetiformis, collagenase and stromelysin-1 may be induced in basal keratinocytes by neutrophil cytokines or by altered cell-matrix interactions through contact of keratinocytes with the matrix due to damaged basement membrane. Stromelysin-1, in particular, may contribute to formation of blisters by degrading basement membrane components.
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PMID:Enhanced expression of interstitial collagenase, stromelysin-1, and urokinase plasminogen activator in lesions of dermatitis herpetiformis. 763 99

We studied the temporal expression of interstitial collagenase, stromelysin-1 and -2, and urokinase plasminogen activator (uPA) mRNAs by in situ hybridization in eight patients with dermatitis herpetiformis. To induce blisters, 50% potassium iodide patch tests were performed, and serial biopsy specimens were taken at 4, 12, and 24 h. Additional samples were taken from occasional spontaneous blisters. Components of the basement membrane, laminin-5, laminin-1, and type VII collagen, were examined immunohistochemically in relation to matrix metalloproteinase expression. At 12 h, when no blisters were seen, uPA mRNA was present in basal keratinocytes in five of eight samples, whereas interstitial collagenase and stromelysin-1 mRNA were not detected. At this time, immunohistochemistry failed to show changes in the basement membrane. At 24 h, uPA, collagenase, and stromelysin-1 mRNAs were present in basal keratinocytes, suggesting an activation of latent forms of the two latter enzymes by the uPA-plasmin pathway. Signal for stromelysin-2 was not detected. Furthermore, disruptions of laminin-1 and type VII collagen were evident. The data suggest that stromelysin-1 and interstitial collagenase may contribute to the degradation of basement membrane in dermatitis herpetiformis. Intracellular staining for laminin-5 co-localized with collagenase mRNA in basal keratinocytes. Because laminin-5 is essential for adhesion of keratinocytes to basement membrane and for establishment of focal adhesions on migrating cells, its production may reflect a regenerative response after the destruction of basement membrane components.
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PMID:Urokinase plasminogen activator is expressed by basal keratinocytes before interstitial collagenase, stromelysin-1, and laminin-5 in experimentally induced dermatitis herpetiformis lesions. 898 Feb 78

Gluten-sensitive enteropathy is characterized by small intestinal damage. The pathogenic mechanisms involved are not precisely understood. There is recent interest in the possibility that matrix metalloproteinases might play a pathogenic role. Using immunohistochemistry technique, we examined the protein expression of matrix metalloproteinases-1, -3, and -9 and the tissue inhibitor metalloproteinase-1 in duodenal biopsies from 30 patients with celiac disease and dermatitis herpetiformis. We demonstrated that the percentage of cells expressing these enzymes and their inhibitor in all patients was significantly greater than in the normal controls (P < 0.0001). This was evident even in patients with a minimal lesion but was most marked in patients with severe damage, mirroring the degree of inflammation in the small intestinal tissue. The increased expression of these enzymes and their inhibitor in the duodenal mucosa of patients with gluten-sensitive enteropathy suggests a role for these enzymes in the tissue remodeling which is a feature of these disorders.
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PMID:Increased protein expression of matrix metalloproteinases -1, -3, and -9 and TIMP-1 in patients with gluten-sensitive enteropathy. 1696 49