Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 (IL-1) is the major immunoregulatory molecule produced by macrophages in response to a variety of environmental insults including chemicals, phagocytosis, bacteria, and bacterial products. Macrophages stimulated by Borrelia burgdorferi produced large quantities of IL-1 when spirochetes were added to macrophages at a ratio of 10 spirochetes per macrophage. The release of IL-1 was dose dependent: a single spirochete per macrophage was sufficient to produce significant quantities of IL-1. Spirochetal lipopolysaccharide was not required for this activity in that polymyxin B in the spirochete-macrophage culture had no effect on IL-1 production. Normal murine fibroblasts cultured with this IL-1 were shown to have an increased rate of DNA synthesis and an increase in secreted collagenase. IL-1 was found in joint fluids from Lyme disease patients. When IL-1 was injected intradermally into the backs of rabbits, the injection sites became indurated, erythematous, and warm to the touch after 4 hrs and annular lesions much like those of erythema chronicum migrans were seen in some animals after 24 hrs. B. burgdorferi is a powerful inducer for IL-1 in vitro, and it is reasonable to presume that it acts similarly in Lyme disease patients. Our results suggest that IL-1 in turn, may play a role in many of the clinical manifestations of Lyme disease.
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PMID:A role for interleukin-1 in the pathogenesis of Lyme disease. 349 83

Many bacteria that spread in the skin produce enzymes that digest extracellular matrix components. Borrelia burgdorferi spreads from a skin inoculation site to form the characteristic erythema migrans skin lesion. It was determined that B. burgdorferi does not produce collagenase, elastase, hyaluronidase, or other enzymes that digest extracellular matrix components. However, B. burgdorferi bound human plasmin, plasminogen (Pgn), and urokinase-type plasminogen activator (uPA). When spirochetes were sequentially incubated with Pgn and uPA, bioactive plasmin was generated on the surface of B. burgdorferi. B. burgdorferi did not produce an endogenous Pgn activator. Fluorochrome-conjugated uPA and Pgn colocalized to the terminus of the spirochete. In a mouse model, uPA-treated B. burgdorferi were more infectious than control spirochetes. Binding of host uPA and Pgn to form a bioactive extracellular matrix protease on B. burgdorferi represents a mechanism that could facilitate dissemination and localization of spirochetes to sites of vascular injury.
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PMID:Binding of human plasminogen and urokinase-type plasminogen activator to the Lyme disease spirochete, Borrelia burgdorferi. 775 1

It has been known that green tea and its components possess significant chemopreventive effects against chemical carcinogens and photo-caused skin tumor formation. In this study, the protective effects of (-)-epigallocatechin-3-gallate (EGCG), a major green tea catechin, on the ultraviolet (UV)-induced skin damage (photoaging) were studied in guinea pigs, hairless mice and human dermal fibroblast cultures. The lipid peroxidation was significantly reduced in the EGCG-treated group. The amount of lipid peroxides produced in the control and EGCG treated group were 838 +/- 144 and 286 +/- 57 nmol/mg at 18 h after UV irradiation, respectively. UVB-induced erythema was also significantly reduced in the EGCG treated group. The erythema relative index of the control and the EGCG treated group were 311 +/- 45 and 191 +/- 49 at 16 h after UV irradiation, respectively. EGCG treatment reduced UVA-induced skin damage (roughness and sagginess) and protected from the decrease of dermal collagen in hairless mouse skin. EGCG treatment blocked the UV-induced increase of collagen secretion and collagenase mRNA level in fibroblast culture. The nuclear transcription factors NF-kappaB and AP-1 binding activities were also inhibited by EGCG treatment.
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PMID:Protective effects of (-)-epigallocatechin-3-gallate on UVA- and UVB-induced skin damage. 1117 86

Repeated exposure to solar ultraviolet radiation results in premature skin aging due, in part, to the degradation of dermal collagen by fibroblast collagenase (matrix metalloproteinase 1 [MMP-1]). We have established TaqMan reverse transcription (RT) polymerase chain reaction (PCR) systems to quantify the messenger RNA (mRNA) expression of MMP-1 and its specific inhibitor TIMP-1 in human buttock skin exposed in vivo to solar simulated radiation (SSR). A time-course study (n = 6) with two minimal erythema doses (MED) of SSR showed maximal induction of MMP-1 and TIMP-1 at 24 h. A dose-response study (n = 6) sampled at 24 h revealed that doses of about 1 MED were necessary to induce expression of MMP-1 mRNA, and our data suggest that the response is saturated at about 2 MED. We also investigated SSR-induced gene expression in the dermis and epidermis separately (n = 5). MMP-1 was present in both tissues, but TIMP-1 was only detected in the dermis. In general, we could only measure MMP-1 mRNA in the nonirradiated control skin of volunteers who were smokers. We hypothesize very large interpersonal variation with MMP-1 induction compared with TIMP-1 which was detected in all the control sites. This suggests a lack of relationship between MMP-1 and TIMP-1 mRNA expression. The large donor variability for MMP-1 in all the studies demonstrates that it is important to analyze gene expression individually.
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PMID:Induction of mRNA for matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 in human skin in vivo by solar simulated radiation. 1142 Oct 72

Humans express three distinct collagenases, MMP-1, MMP-8, and MMP-13, that initiate degradation of fibrillar type I collagen. We have previously reported that ultraviolet irradiation causes increased expression of MMP-1, but not MMP-13, in keratinocytes and fibroblasts in human skin in vivo. We report here that ultraviolet irradiation increases expression of MMP-8 in human skin in vivo. Western analysis revealed that levels of the full-length, 85 kDa proenzyme form of MMP-8 increased significantly within 8 h post ultraviolet irradiation (2 minimal erythema doses). Increased full-length MMP-8 protein was associated with infiltration into the skin of neutrophils, which are the major cell type that expresses MMP-8. Immunofluorescence revealed coexpression of MMP-8 and neutrophil elastase, a marker for neutrophils. Immunohistology demonstrated MMP-8 expression in neutrophils in the papillary dermis between 4 and 8 h post ultraviolet irradiation, and in the epidermis at 24 h post radiation. MMP-8 mRNA expression was not detected in nonirradiated or ultraviolet-irradiated human skin, indicating that increased MMP-8 following ultraviolet irradiation resulted from preexisting MMP-8 protein in infiltrating neutrophils. Pretreatment of skin with the glucocorticoid clobetasol, but not all-trans retinoic acid, significantly blocked ultraviolet-induced increases in MMP-8 protein levels, and neutrophil infiltration. In contrast, all-trans retinoic acid and clobetasol were equally effective in blocking ultraviolet induction of MMP-1 and degradation of collagen in human skin in vivo. Taken together, these data demonstrate that ultraviolet irradiation increases MMP-8 protein, which exists predominantly in a latent form within neutrophils, in human skin in vivo. Although ultraviolet irradiation induces both MMP-1 and MMP-8, ultraviolet-induced collagen degradation is initiated primarily by MMP-1, with little, if any, contribution by MMP-8.
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PMID:Ultraviolet irradiation increases matrix metalloproteinase-8 protein in human skin in vivo. 1151 Dec 97

A number of studies indicate that matrix metalloproteinase might be involved in photoaging, but little is known about their direct contribution to ultraviolet-induced histologic and morphologic changes in the skin in vivo. This study reports the relationship between changes of matrix metalloproteinase activities and ultraviolet B-induced skin changes in hairless mouse. The role of matrix metalloproteinase in the skin changes was studied by topical application of a specific matrix metalloproteinase inhibitor. The backs of mice were exposed to ultraviolet B three times a week for 10 wk. Histologic studies showed that the basement membrane structure was damaged, with epidermal hyperplasia, in the first 2 wk of ultraviolet B irradiation, followed by the appearance of wrinkles, which gradually extended in the latter half of the ultraviolet B irradiation period. We observed enhancement of type IV collagen degradation activity, but not collagenase or matrix metalloproteinase-3 activity, in extracts of ultraviolet B-irradiated, wrinkle-bearing skin. Gelatin zymographic analysis revealed that gelatinases, matrix metalloproteinase-9 and matrix metalloproteinase-2, were significantly increased in the extract. In situ zymographic study clarified that the activity was specifically localized in whole epidermis of ultraviolet B-irradiated, wrinkled skin in comparison with normal skin. The activity was induced around the basal layer of the epidermis by a single ultraviolet exposure of at least one minimal erythema dose. Furthermore, topical application of a specific matrix metalloproteinase inhibitor, CGS27023A, inhibited ultraviolet B-induced gelatinase activity in the epidermis, and its repeated application prevented ultraviolet B-induced damage to the basement membrane, as well as epidermal hyperplasia and dermal collagen degradation. Ultraviolet B-induced wrinkles were also prevented by administration of the inhibitor. These results, taken together, suggest that ultraviolet B-induced enhancement of gelatinase activity in the skin contributes to wrinkle formation through the destruction of basement membrane structure and dermal collagen in chronically ultraviolet B-exposed hairless mouse, and thus topical application of matrix metalloproteinase inhibitors may be an effective way to prevent ultraviolet B-induced wrinkle formation.
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PMID:Possible involvement of gelatinases in basement membrane damage and wrinkle formation in chronically ultraviolet B-exposed hairless mouse. 1253 9

Human skin is exposed to solar ultraviolet radiation. Ultraviolet radiation damages human skin and results in an old and wrinkled appearance, called photoaging. We have previously reported that molecular mechanisms by which ultraviolet light causes photoaging involve activation of growth factor and cytokine receptors in keratinocytes and dermal cells. They lead to downstream signal transduction through activation of mitogen-activated protein kinase (extracellular signal-regulated kinase, c-jun N-terminal protein kinase, and p38) pathways. These signaling pathways converge in the nucleus of cells to form an activated complex of transcription factor activator protein 1 (cFos/cJun), which induces matrix metalloproteinases that degrade skin connective tissue. In addition to cell surface receptor activation, generation of reactive oxygen species by ultraviolet radiation is believed to be critical in triggering mitogen-activated protein kinase pathways. We investigated the ability of (i) ultraviolet irradiation to generate reactive oxygen species in human skin in vivo; and (ii) genistein, which possesses both tyrosine kinase inhibitory and antioxidant activities, and n-acetyl cysteine, which can be converted into the endogenous antioxidant glutathione, to impair responses to ultraviolet light that eventuate in photoaging in human skin in vivo. Ultraviolet irradiation caused a rapid and significant increase in hydrogen peroxide levels in human skin in vivo. Pretreatment of human skin with genistein inhibited ultraviolet-induced epidermal growth factor receptor tyrosine kinase activity, whereas n-acetyl cysteine did not. Genistein inhibited ultraviolet induction of both extracellular signal-regulated kinase and cJun N-terminal protein kinase activities. n-Acetyl cysteine inhibited extracellular signal-regulated kinase but not cJun N-terminal protein kinase activation. Both genistein and n-acetyl cysteine prevented ultraviolet induction of cJun protein. Consistent with this, genistein and n-acetyl cysteine blocked ultraviolet induction of cJun-driven enzyme, collagenase. Neither genistein nor n-acetyl cysteine acted as sunscreens as they had no effect on ultraviolet-induced erythema. These data indicate that compounds similar to genistein and n-acetyl cysteine, which possess tyrosine kinase inhibitory and/or antioxidant activities, may prevent photoaging.
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PMID:Topical N-acetyl cysteine and genistein prevent ultraviolet-light-induced signaling that leads to photoaging in human skin in vivo. 1271 90

Punch biopsies of human skin were obtained 1 day after irradiation with two minimal-erythema doses (MED) from either a UVB light source or a Solar Simulator and incubated in organ culture for 72 h. Organ culture fluids obtained at 24, 48 and 72 h were analyzed for collagenolytic activity and for reactivity with antibodies to matrix metalloproteinase-1 (MMP-1; interstitial collagenase) and MMP-13 (collagenase-3). High levels of collagenolytic activity were seen in organ culture fluid from skin exposed to either light source. MMP-1 was strongly induced in parallel, increasing from less than 100 ng/ml in organ culture fluid from control skin to approximately 1.1 microg/ml in culture fluid from UV-treated skin. Whereas most of the detectable MMP-1 in control culture fluid was represented by the latent form of the enzyme, approximately 50% of the enzyme was present as the active form in organ culture fluid of UV-exposed skin. In contrast, there was no detectable MMP-13 in control organ culture fluid and very little change after UV exposure (less than 100 ng/ml in both cases). Finally, neutralization studies with a blocking antibody to MMP-1 removed 95 +/- 4% of the collagenolytic activity in the organ culture fluid from UV-treated skin. These findings strongly implicate MMP-1 rather than MMP-13 as the major collagenolytic enzyme responsible for collagen damage in photoaging.
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PMID:Matrix metalloproteinase-1 is the major collagenolytic enzyme responsible for collagen damage in UV-irradiated human skin. 1292 47

Chronic ultraviolet irradiation leads to photoaging in human skin, which is associated with degradation of connective tissue. This is partly due to the fibroblast collagenase (matrix metalloproteinase 1 [MMP-1]). Using complementary DNA array technique we demonstrate that after UV irradiation, MMP-1, MMP-3 and the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) are time-dependently induced on the messenger RNA level in dermal fibroblasts in vitro and in vivo in human buttock skin. This increase in gene expression is paralleled by an increase of latent and active MMP-1 protein after low-dose UV-A exposure in vitro. In vivo the concentration of latent MMP-1 in suction blister fluids peaks 24 h after irradiation with 2 minimal erythema doses of solar simulated radiation. However, only a small proportion of MMP-1 in vitro (5.5 +/- 1.5%) and in vivo is active, whereas the majority of MMP-1 remains in its inactive proform. Interestingly, in suction blister fluid the concentration and duration of TIMP-1 expression exceeds that of MMP-1. Taken together, these data indicate that MMP-1 activity is tightly regulated transcriptionally and posttranscriptionally. Furthermore, the pronounced individual differences in all targets investigated provide a possible explanation for the different susceptibility of individuals to UV exposure and, thus, to the clinical features of photodamage.
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PMID:Tight control of matrix metalloproteinase-1 activity in human skin. 1462 63

Photomodulation is a process that manipulates or regulates cell activity using light sources without thermal effect. Previous studies of LED photomodulation have shown skin textural improvement accompanied by increased collagen deposition with reduced MMP-1 (collagenase) activity in the papillary dermis. The purpose of this study was to investigate a separate cohort of patients (N =93) with a wide range of Fitzpatrick skin types treated by LED photomodulation using the Gentlewaves full panel 590 nm high energy LED array with a specific sequence or code of pulsing in the millisecond domain. Results showed improvement of signs of photoaging in 90%. The majority of patients demonstrated improvement in peri-ocular wrinkles, reduction in Fitzpatrick photoaging classification, global skin texture and background erythema, and pigmentation. No side effects were noted. LED photomodulation is a safe and effective non-painful non-ablative modality for improvement of photoaging.
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PMID:A novel non-thermal non-ablative full panel LED photomodulation device for reversal of photoaging: digital microscopic and clinical results in various skin types. 1562 43


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