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)

The effects of recombinant human Interleukin-1 alpha (IL-1 alpha), Interleukin-1 beta (IL-1 beta), and Tumor Necrosis Factor-alpha (TNF-alpha) on collagen biosynthesis were studied in vitro using dermal fibroblast cultures. Both forms of IL-1 and TNF-alpha induced a dose-dependent inhibition of both types I and III collagen synthesis, as measured by radioimmunoassay, gel electrophoresis, or collagenase-sensitive material. This effect was accompanied by a significant release of prostaglandin E2 into the culture medium. However, indomethacin, a potent inhibitor of prostaglandin synthesis, could not prevent the inhibitory effect of the three cytokines on collagen synthesis. Measurement of type I and type III procollagen mRNA levels in IL-1 treated cells revealed that both IL-1 alpha and IL-1 beta were potent enhancers of procollagen gene expression at pretranslational level. On the other hand, TNF-alpha was found to reduce the steady-state levels of type I and III procollagen mRNA in a dose-dependent manner. Quantitation of IL-1 beta and TNF-alpha transcripts following TNF-alpha treatment of fibroblasts indicated that this cytokine can induce IL-1 beta gene expression in these cells. By contrast, TNF-alpha mRNA remained at a constant level after TNF-alpha exposure. These data suggest that IL-1 and TNF-alpha, two cytokines that share several biologic activities, modulate collagen deposition in dermal fibroblasts by mechanisms that are clearly different: TNF-alpha appears to act at a transcriptional level to inhibit collagen synthesis, whereas IL-1 inhibitory action involves important translational regulation, still unknown, that counterbalances its stimulatory effect on procollagen mRNA levels. Moreover, our data suggest the existence of local fibroblastic cytokine production that may be involved in the modulation of extracellular matrix deposition.
J Invest Dermatol 1991 Feb
PMID:Comparative effects of interleukin-1 and tumor necrosis factor-alpha on collagen production and corresponding procollagen mRNA levels in human dermal fibroblasts. 199 84

Lattices made of collagen and fibroblasts can be used as dermal equivalents to grow human keratinocytes in vitro. When these cultures are performed in a medium containing delipidized serum, the lattice is eventually degraded by the growing epithelium. The digestion of the dermal equivalent is due to the secretion of a collagenase by the keratinocytes. This degradation does not occur in cultures containing total serum or supplemented with retinoic acid. We show in this paper that retinoic acid inhibits the secretion of this keratinocyte collagenase in a dose-dependent manner. In the light of this result, the possible involvement of collagenase inhibition in the therapeutic effect of retinoic acid in skin disorders and skin aging must be considered.
J Invest Dermatol 1990 Jan
PMID:Retinoic acid inhibits the production of collagenase by human epidermal keratinocytes. 215 79

Human keratinocytes in culture are known to produce collagenase. As part of studies to ascertain the physiologic stimuli for collagenase production by keratinocytes, we wanted to determine whether extracellular matrix could modulate the production of collagenase in vitro. Immunoprecipitable collagenase from the conditioned medium of cells grown on different types of matrix was measured. Metabolically labeled human keratinocytes were cultured in 0.1 mM calcium in serum-free medium on colloidal gold-coated coverslips plus type IV collagen, type I collagen, or laminin or in the absence of matrix. Immunoprecipitation of the conditioned medium with anti-collagenase antiserum was performed and the immunoprecipitates were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, fluorography, and densitometry. The keratinocytes cultured on type IV or type I collagen produced more collagenase than did those cultured on laminin or in the absence of matrix. This effect did not reflect a general increase in secreted proteins, because the production of tissue inhibitor of metalloproteinase, or TIMP, did not increase under the same conditions. Phagocytosis of the gold salts by the keratinocytes migrating on types I or IV collagen did not account for the increased collagenase produced by these cells since the effect persisted in the absence of the colloidal gold and phagocytosis of latex beads did not augment collagenase production.
J Invest Dermatol 1990 Mar
PMID:Enhanced synthesis of collagenase by human keratinocytes cultured on type I or type IV collagen. 215 73

Peak (1 and 2 d) and healing (3, 6, and 10 d) inflammatory lesions were produced in rabbits by the topical application of the military vesicant, bis(2-chloroethyl)sulfide, commonly called sulfur mustard (SM). SM produces an acute sterile dermal inflammatory reaction with little or no necrosis, except in the epidermis, which dies during the first day. After an animal was killed, its lesions were excised intact, as full-thickness 1.0-cm2 explants. They were then organ-cultured for 3 d in order to maintain the viability of both local and infiltrating cells. The extracellular fluid in each lesion equilibrated with the culture fluid, which was collected daily and analyzed for collagenase and proteoglycanase activities. These metalloproteinase activities were measured after we had i) destroyed the alpha-macroglobulin inhibitors with KSCN, ii) destroyed the tissue inhibitor of metalloproteinases (TIMP) by reduction and alkylation, and iii) activated the latent proteinase activity with aminophenylmercuric acetate (APMA). Hydroxyproline-containing peptides and glycosaminoglycans (GAG) released into the culture fluids were also measured as indicators of local collagenase and proteoglycanase activity within the inflammatory lesions. In general, the levels of both the metalloproteinases and the products of their activity were higher in second- and third-day culture fluids than in first-day culture fluids, and higher in fluids from SM lesions than in those from normal skin. The activated fibroblast was apparently the major cell type producing the collagenase and proteoglycanase. The hydrolysis of collagen and ground substance occurs pericellularly. An excess of inhibitors exists outside the pericellular region. The daily change in culture fluids apparently decreased such inhibitors, so that by the second and third day of culture we could detect the changes in pericellular enzyme activity that were not detectable on the first day of culture. As the inflammatory lesions healed, the extracellular enzyme products (hydroxyproline and GAG) increased more than the enzymes that produced these products. With healing, a decrease occurs in the extravasation of all serum components, especially the large ones such as the alpha-macroglobulin inhibitors. We propose that during healing, the decrease in these inhibitors allows the metalloproteinases to begin the remodeling process, and that during the peak phase of inflammation, these same inhibitors protect extracellular matrix against hydrolysis by such proteinases.
J Invest Dermatol 1990 Dec
PMID:Extracellular collagenase, proteoglycanase and products of their activity, released in organ culture by intact dermal inflammatory lesions produced by sulfur mustard. 217 50

We examined the direct effect of interleukin-1 (IL-1) on the collagenase production by epidermolysis bullosa (EB) fibroblasts. Addition of IL-1 at concentrations of 2.5 x 10(-4) units/ml or below in the culture media greatly enhanced collagenase production by two cell lines of recessive dystrophic EB (RDEB) fibroblasts. They produced 4.82 +/- 0.04 to 5.93 +/- 0.39 units/ml of enzyme, as compared to 0.02 +/- 0.07 units/ml in the absence of IL-1. In contrast, collagenase production by two cell lines of dominant dystrophic EB (DDEB) and normal fibroblasts was not, or only slightly, increased up to 0.69 +/- 0.28 units/ml. IL-1 concentrations of 2.5 x 10(-3) units/ml or higher failed to induce collagenase production by all fibroblasts. 3H-thymidine uptake increased by about 110-376% of control after IL-1 treatment. In addition, these data were obtained using fibroblasts of the 13-15 passages, suggesting that the property might be determined genetically. Although RDEB seems to be a wide heterogeneous group, the present data strongly suggest that the property may be specific to and characteristic of some types of RDEB cells.
Arch Dermatol Res 1990
PMID:Interleukin-1 induces collagenase production by recessive dystrophic epidermolysis bullosa fibroblasts. 217 79

Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits the proliferation and certain biosynthetic activities of fibroblasts derived from normal human skin. Fibroblasts from the skin of patients with keloids, scleroderma and morphoea were cultured in vitro in the presence and absence of pentoxifylline (100-1000 micrograms/ml) to determine whether it inhibits fibroblast proliferation and the production of collagen, glycosaminoglycans (GAG), fibronectin and collagenase activity. The exposure of subconfluent fibroblast cultures to pentoxifylline resulted in non-lethal, dose-dependent reductions in serum-driven fibroblast proliferation, with 1000 micrograms/ml pentoxifylline virtually negating the proliferative effect of serum on the cells. The fibroblasts assayed as confluent cultures produced reduced amounts, by up to 95%, of collagen and GAG, dependent on the concentration of pentoxifylline, both in the presence and absence of serum. Pentoxifylline similarly inhibited the fibronectin production by keloid and scleroderma fibroblasts, but had no effect on collagenase activity.
Br J Dermatol 1990 Sep
PMID:Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin. 220 72

The cultured hair cells from 4-day-old C3H mice were studied by electron microscopy. The hair roots isolated from the skin by collagenase digestion were dispersed into a cell suspension by treatment with a mixture of trypsin and ethylenediaminetetraacetate. The cells were cultured in MCDB-153 (a medium containing seven growth factors) for 1, 3, 6 or 13 days. The number of cultured cells on day 3 was twice that on day 1, and stayed at the same level until day 13. By electron microscopy, some of the cells cultured for 1 day were seen to be undifferentiated and others already showed differentiation into various hair structures. Such differentiated cells disappeared on day 3 and most of the cells cultured for 3 days were undifferentiated. Cell cultured for 6 days were differentiated showing inner root sheath cell, hair cortical cell and medulla cell structures. The characteristics of these cultured cells corresponded well to those of in vivo cells of the hair tissues from the back skin of 7-day-old C3H mice. On day 13 degeneration occurred in the cultured cells. In none of these cultures were mesenchymal cells, such as fibroblasts, found. The present electron microscopic study reveals that immature cells obtained from mouse hair tissues proliferate in vitro and differentiate into several subpopulations corresponding to those of in vivo cell layers of hair tissues. The present culture technique may be useful for studies of hair cell growth and differentiation.
Arch Dermatol Res 1990
PMID:Electron microscopic study of cultured cells from the murine hair tissues: cell growth and differentiation. 226 Aug 83

Although Werner's syndrome (WS) is a premature aging disease and its fibroblasts typically grow poorly in culture, WS may cause abnormalities in connective tissue metabolism that are seldom seen in normal aging, such as scleroderma-like skin. In a preliminary report, we described increased collagen synthesis in fibroblasts derived from two WS patients. The present study was undertaken to determine the degree of the regulation of collagen gene expression in dermal fibroblasts from two other patients. Overproduction of collagenase sensitive protein was observed in WS fibroblasts. Collagen m-RNA levels, that were determined by hybridization of RNA blots with specific cDNA were about 2 times greater than those in the control cells. These results suggest that control of collagen synthesis in WS fibroblasts is altered at the transcriptional level.
J Invest Dermatol 1990 Feb
PMID:Increased collagen synthesis accompanying elevated m-RNA levels in cultured Werner's syndrome fibroblasts. 229 93

The connective tissue adjacent to basal cell carcinomas (BCC) is frequently abnormal and contains increased numbers of fibroblasts and increased extractable collagenase. To determine whether BCC could produce these alterations by releasing mediators that regulated fibroblast function, we established BCC in culture and tested the ability of their culture supernatants to alter fibroblast proliferation and production of collagenase. Using tissue culture plates coated with type IV collagen and containing x-irradiated 3T3 feeder cells, we established epithelial colonies from 47% of the BCC cultured. The BCC-derived colonies differed from normal epidermal cell colonies in their morphology, growth rate, and keratin production. Culture supernatants from 4 out of 5 confluent BCC-derived colonies contained factors that stimulated fibroblasts to proliferate and release collagenase. These findings show that BCC-derived epidermal cell colonies release mediators which alter fibroblast functions and suggest that some of the connective tissue changes associated with BCC in vivo are the result of BCC-fibroblast interactions.
J Invest Dermatol 1985 Nov
PMID:Establishment of basal cell carcinoma in culture: evidence for a basal cell carcinoma-derived factor(s) which stimulates fibroblasts to proliferate and release collagenase. 241 70

The skin is the major site on anaphylaxis, and cutaneous mast cells have an important role in its reactions. The isolation and purification of rat cutaneous mast cells are described here. Rat abdominal skin was digested with collagenase and hyaluronidase, and centrifuged with Percoll. The buoyant density of cutaneous mast cells was high, and relatively pure mast cells were obtained. The purity of cutaneous mast cells was 74% +/- 2.4% before and 50.0% +/- 6.4% after Percoll density centrifugation; peritoneal mast cells revealed 5.8% +/- 1.3% purity before and 61.0% +/-10.6% purity after the same procedure. The isolated cutaneous cells released 21.3% +/- 3.8% histamine and the peritoneal mast cells released 55.5% +/- 3.8% histamine upon stimulation with 10 micrograms/ml compound 48/80. These findings suggest that there are functional subsets of connective tissue mast cells.
Arch Dermatol Res 1988
PMID:Purification of rat cutaneous mast cells with Percoll density centrifugation. 246 Nov 70


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