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

---

Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat resident peritoneal macrophages in primary culture were found to elaborate a mitogenic factor (or factors) for rat osteoblast-like cells and chondrocytes but not for skin fibroblasts. Growth-promoting activity appeared in the incubation medium within the first 20 hr of macrophage culture and was released in amounts that paralleled the number of macrophages per culture. After their proliferative response, as judged by increases in DNA synthesis and cell number, the osteoblast-like cells became enriched in alkaline phosphatase, an index of osteoblast specialization. The macrophage-derived activity was nondialyzable and heat-stable, and it was eliminated by exposure to trypsin. Inhibition of prostaglandin cyclooxygenase failed to modify its generation. Partial purification (Amicon filter concentration, gel filtration) disclosed principal peaks of activity corresponding to Mr of 43,000 and 10,000. The crude conditioned medium and the Mr 43,000-peak, but not the low-molecular-weight peak, exhibited interleukin 1 activity, as judged by the ability to stimulate the proliferation of mouse thymic lymphocytes. The macrophage-derived growth factor described herein may participate in bone remodeling and repair and in primary bone and cartilage growth.
...
PMID:Macrophage-derived growth factor for osteoblast-like cells and chondrocytes. 661 52

An interleukin 2-independent murine T cell line (BFS) was isolated that produced immune interferon after stimulation with phorbol 12-myristate 13-acetate. The BFS cell line did not produce detectable levels of interleukin 1, interleukin 2, B cell growth factor, macrophage-granulocyte colony-stimulating factor, macrophage-activating factor, or T cell replacing factor. Maximal interferon was induced 48 hr after stimulation with phorbol myristate acetate at 10-100 ng/ml. Production of interferon by phorbol myristate acetate-stimulated BFS cell cultures was synergistically increased by the addition of EL4 thymoma cell culture supernatants. BFS-derived interferon activity was sensitive to pH 2 treatment and was neutralized with antiserum to immune interferon but was resistant to heating at 56 degrees C and to treatment with antiserum to type I interferon. In addition, the interferon activity was sensitive to trypsin but resistant to RNase. BFS-derived interferon had an apparent molecular weight of 48,000 and a pI of 5.5-6.0. Each of these properties is consistent with the conclusion that the BFS cell line produces immune interferon after stimulation with phorbol myristate acetate.
...
PMID:Production of immune interferon by an interleukin 2-independent murine T cell line. 681 57

In severe acute pancreatitis (SAP), the mechanisms leading to adult respiratory distress syndrome (ARDS) are usually attributed to the release of active enzymes and vasoactive substances from the pancreas. Thoracic duct drainage has been proposed as a means of removing the portion of these substances that drain through retroperitoneal lymphatics before they reach the systemic circulation. This technique was used in six patients with ARDS complicating SAP. The levels of proinflammatory cytokines (tumor necrosis factor-alpha [TNF alpha], interleukin-1 [IL-1], and interleukin-6 [IL-6]), neutrophil enzymes (myeloperoxidase and lactoferrin), and pancreatic enzymes (amylase, lipase and trypsin) were measured in plasma and lymph in the first 24 h of ARDS and then on Day 2, Day 4, and at the end of the drainage (Day 8). High plasma concentrations of these products were measured. A moderate lymph-to-plasma gradient was observed for IL-6, lipase, and trypsin, while similar levels in plasma and lymph were recorded for the other substances. Plasma levels of pancreatic enzymes were weakly correlated with the lung injury score and lymph level of cytokines. These results suggest that in patients with ARDS due to SAP, cytokines as well as pancreatic enzymes could contribute to the development of the lung injury, and that lymphatics are potential vectors of these mediators.
...
PMID:Lymphatic release of cytokines during acute lung injury complicating severe pancreatitis. 758 88

The enzyme collagenase (EC 3.4.24.7), a key mediator in biological remodeling, can be induced in early-passage fibroblasts by a wide variety of agents and conditions. In contrast, at least some primary tissue fibroblasts are incompetent to synthesize collagenase in response to many of these stimulators. In this study, we investigate mechanisms controlling response to two of the conditions in question: (i) trypsin or cytochalasin B, which disrupt actin stress fibers, or (ii) phorbol 12-myristate 13-acetate (PMA), which activates growth factor signaling pathways. We demonstrate that collagenase expression stimulated by trypsin or cytochalasin B is regulated entirely through an autocrine cytokine, interleukin 1 alpha (IL-1 alpha). The IL-1 alpha intermediate also constitutes the major mechanism by which PMA stimulates collagenase expression, although a second signaling pathway(s) contributes to a minor extent. Elevation of the IL-1 alpha level in response to stimulators is found to be sustained by means of an autocrine feedback loop in early-passage fibroblast cultures. In contrast, fibroblasts freshly isolated from the tissue are incompetent to activate and sustain the IL-1 alpha feedback loop, even though they synthesize collagenase in response to exogenous IL-1. We conclude that this is the reason why tissue fibroblasts are limited, in comparison with subcultured fibroblasts, in their capacity to synthesize collagenase. Activation of the IL-1 alpha feedback loop, therefore, seems likely to be an important mechanism by which resident tissue cells adopt the remodeling phenotype.
...
PMID:Competence for collagenase gene expression by tissue fibroblasts requires activation of an interleukin 1 alpha autocrine loop. 762 17

The stimulated release of von Willebrand factor (vWF) from endothelial cells by secretagogues such as thrombin is associated with the translocation of Weibel-Palade bodies to the cell membrane and the surface expression of P-selectin (also known as GMP 140, PADGEM and CD 62). P-selectin, which is stored in Weibel-Palade bodies, is a neutrophil and monocyte adhesion molecule important in the initiation of inflammation. We have developed a simple assay for the detection of P-selectin on endothelial cells using indirect immunofluorescence and flow cytometry and have confirmed that this is temporally related to vWF release. The assay has been used to demonstrate that IL-1 does not cause Weibel-Palade body degranulation but that trypsin does. This has implications for the use of passaged endothelial cells in the study of vWF release and the assay has numerous possible applications in study of mechanisms of stimulated vWF release.
...
PMID:von Willebrand factor release and P-selectin expression is stimulated by thrombin and trypsin but not IL-1 in cultured human endothelial cells. 769 90

Human chorion, but not amnion, tissue explants produced substantial quantities of neutrophil chemoattractant in response to interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF alpha). This suggested that chorion is one of the chemoattractant producing tissues. Therefore, the biochemical properties and the regulation of a chemoattractant in human chorionic cells were examined. IL-1 alpha and TNF alpha stimulated human chorionic cells to produce neutrophil chemotactic factor in both a dose- and time-dependent manner. This chemotactic factor was a heat-stable and trypsin-sensitive protein with an apparent molecular weight of 10000, and it was also immunologically identified as a chemotactic cytokine of the human IL-8 family. Immunohistochemical observations with IL-1 alpha- and TNF alpha-treated chorion explants indicated that trophoblasts and stromal cells, including fibroblast-like and macrophage-like cells, but not endothelial cells, were characterized as IL-8-producing cells. From these observations, it is very likely that both IL-1 and TNF alpha may participate in the production of chemotactic factor/IL-8 in pre-term parturition, accompanied by an intraamniotic infection, along with their known promotive effect on the production of matrix metalloproteinases, which is connected with the destruction of matrix components of fetal membranes.
...
PMID:Stimulation of the biosynthesis of interleukin 8 by interleukin 1 and tumor necrosis factor alpha in cultured human chorionic cells. 770 64

The supernatant of a cell line of squamous cell carcinoma of the head and neck (SCCHN), PCI-50, was previously shown to induce activation, promote proliferation and increase antitumor cytotoxicity of freshly purified human natural killer (NK) cells and CD4+ T lymphocytes [Arch Otolaryngol Head Neck Surg (1994) in press]. This supernatant was found also to promote the growth of a variety of hematopoietic cell lines, including Jurkat, THP-1, K562, NK-92 or Epstein-Barr-virus-transformed B cell lines. The Jurkat cell line was selected as a reporter cell in an 18-h proliferation assay established to measure the growth-promoting activity of PCI-50 supernatant. The presence of soluble tumor-derived factors able to induce proliferation of Jurkat cells was demonstrated in the supernatant produced by several other SCCHN cell lines but not in that produced by a gastric cancer cell line (HR) or renal cell carcinoma line (5117G8). The growth-promoting PCI-50 supernatant was shown to contain 28 +/- 0.5 pg/ml interleukin-6 (IL-6) in vitro but was negative for interferon gamma, IL-1, IL-2, IL-4, tumor necrosis factor alpha, granulocyte/macrophage-colony-stimulating factor and IL-12. The addition of any of these recombinant cytokines to Jurkat cell cultures did not significantly promote growth, while PCI-50 supernatant was consistently growth-stimulatory. This supernatant neither enhanced intracellular Ca2+ concentration in Jurkat cells nor induced up-regulation of activation antigens on the cell surface, although it supported growth of Jurkat cells in the absence of IL-2. The growth-promoting activity in the PCI-50 supernatant was acid-labile at pH 2 for 4 h, heat-resistant at 96 degrees C for 1 h and sensitive to treatments with trypsin and pepsin. Preincubation of the PCI-50 producer cells with tunicamycin or cyclohexamide reduced the level of growth-promoting activity in the supernatant. A partial purification of this activity was achieved using Amicon filtration, chromatography on concanavalin-A-Sepharose and then a hydroxyapatite column and high-pressure liquid chromatography gel filtration. The partially purified glycoprotein had a molecular mass of 50-70 kDa, as determined by gel filtration.
...
PMID:Proliferation of hematopoietic cell lines induced by a soluble factor derived from human squamous cell carcinomas of the head and neck. 800 Oct 29

To determine the intrauterine defensive role of urinary trypsin inhibitor (UTI), we studied the effects of UTI in amniotic fluid, fetal membranes and myometrium. The level of UTI was 94 +/- 34 U/ml in neonatal urine (compared to adult urine 8.0 +/- 6.0 U/ml) and 88 +/- 37 U/ml in amniotic fluid. This may indicate that the main source of UTI in the amniotic fluid is the fetal urine. UTI was found to be concentrated in vernix, fetal intestine, amniotic membranes and uterine myometrium. Immunostaining of term amnion revealed a dark staining for UTI, whereas in premature deliveries UTI staining was markedly decreased. In myometrium, the concentration of UTI was found to be increased during pregnancy compared to non pregnant myometrium. Also, placentas were well stained for UTI in term pregnancy. Thus UTI has an important role in amniotic fluid, fetal membranes, placenta and uterine muscles. UTI has an inhibitory effect on several enzymes and cytokines. UTI was found to inhibit neutrophil elastase activity as well as trypsin activity. Its inhibitory activity was increased in the presence of lipid. LPS stimulated amnion cells trapped more UTI than unstimulated amnion cells. UTI in amnion cells was released after addition of 1% meconium solution. UTI was also found to inhibit the effect of IL-1, TNF and interleukin-8 on amnion. These results indicate that UTI localized in amnion is important in the protection of fetal membrane especially against bacterial infections and cytokines. It is known that endothelin (ET), prostaglandin F2 alpha (PGF2 alpha) and oxytocin can induce uterine contraction. UTI could inhibit uterine contractions stimulated by ET, PGF2 alpha and oxytocin in isometric contraction test. UTI could also inhibit cervical maturation induced by interleukin-8. Therefore UTI is essential for maintenance of pregnancy. From the isometric contraction tests, we assumed that UTI might works through regulation of calcium entry or availability in the cells. Initial increase in intracellular calcium was also inhibited by UTI pre incubation dose dependantly. We examined the change in intracellular calcium at single cell level by digital image analysis with Fura 2AM as a calcium probe. At resting level UTI incubation did not produce any significant changes in intracellular free calcium. Thrombin, LPS, interleukin-8 and ET-1, known calcium agonists could increase intracellular calcium in fibroblasts, amnion and uterine myocytes. Whereas as the same doses of those known calcium agonists could not change the intracellular free Ca2+ concentrations in UTI pre incubated fibroblasts, amnion cells and uterine smooth muscle cells.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:[Intrauterine defensive mechanism of amniotic fluid and fetal membranes]. 808 4

alpha 1-Antitrypsin (alpha 1-AT) and alpha 1-antichymotrypsin (alpha 1-ACHY) are closely related protease inhibitors, synthesized primarily by the liver, which play major roles in modulation of the inflammatory response. Previously, we had shown that MCF-7 human breast cancer cells were able to synthesize active alpha 1-AT and alpha 1-ACHY and that the synthesis of both inhibitors varied among different MCF-7 sublines. We now show that when MCF-7(ML) cells (a subline synthesizing low levels of alpha 1-AT) are grown in soft agar in medium depleted of its trypsin inhibitory capacity (i.e. alpha 1-AT-free), addition of alpha 1-AT (50 micrograms/ml) significantly reduces colony formation in both the presence and absence of estradiol (34% and 44%, respectively). Under these conditions, incubation with 10(-7) M estradiol alone increased colony formation 2- to 3-fold. Colony formation was also significantly reduced by serum leukocyte protease inhibitor, which, like alpha 1-AT, is a potent inhibitor of elastase-like enzymes. We also found that a variety of inflammatory mediators, cytokines, and steroid hormones are able to stimulate synthesis of alpha 1-AT and alpha 1-ACHY by MCF-7 cells. Stimulation by interleukin-6 (IL-6; 200 U/ml), epidermal growth factor (4 nM), and estradiol (10(-7) M) was 2- to 3-fold, whereas stimulations by tetradecanoylphorbol-13-acetate (TPA; 80 nM) and IL-1 (10 U/ml) were 2- to 5-fold and 5- to 10-fold, respectively. In each instance, protein synthesis, monitored by immunoprecipitation of 35S-labeled proteins followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and steady state mRNA levels, monitored by Northern blot analysis with specific cDNA probes, increased to the same extent. Consistent with their ability to stimulate alpha 1-AT synthesis, TPA and IL-1 reduced colony formation in the absence of estradiol by 65% and 63%, respectively. In addition, the effects of both TPA and IL-1 could be reversed by antibody to alpha 1-AT. These results suggest that local synthesis of alpha 1-AT and possibly other protease inhibitors may be important in regulating the tumorigenic potential of MCF-7 breast cancer cells.
...
PMID:alpha 1-Antitrypsin- and anchorage-independent growth of MCF-7 breast cancer cells. 836 78

A number of cytokines have been reported to increase the cell motility (scatter) of cohesive cell colonies. We report here a novel scattering factor produced by human monocytes. Media from both stimulated and non-stimulated human monocytes or the monocytic cell line, U937, increased the cell motility of 2 human colon-cancer cell lines, HT115 and HT29, but not the canine epithelial cell line MDCK. Motility was assayed by cell dissociation from carrier beads and colony scattering. HT115 cells were strongly scattered by the conditioned media but not by interleukins IL-1, 2, 4, 6, 8, 10, TNF alpha, TGF beta, EGF, GM-CSF, IGF-I, PDGF, interferon-gamma. This factor is distinct from hepatocyte growth factor/scatter factor (HGF/SF), since the activity was not blocked by anti-HGF/SF antibody. The activity was reduced by treatment with acid, heat, trypsin and dithiothreitol; this, together with gel filtration, suggests that the factor is a protein (MW 40 to 60 kDa). This new factor, which is secreted from monocytes and the monocytic cell line, U937, has the ability to increase the motility of cancer cells and may be important in controlling the behaviour of tumours in vivo.
...
PMID:Monocyte-conditioned media possess a novel factor which increases motility of cancer cells. 842 96


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---