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)

By means of biological in vitro assay collagenolytic activity of normal peripheral lymphocytes was compared to that of EBV-infected lymphoblastoid cell lines: the EBV-producing P3HR1 cells and the non-productive Raji cells. While normal lymphocytes and Raji cells revealed only traces of activity, significantly increased (p less than 0.001) collagenolytic activity was detected in samples of P3HR1, the cell-free EBV-suspension alone showed no collagenolysis. The described enzymatic activity was fully inhibited by 0-phenanthroline and EDTA indicating collagenase action. As main explanations for the phenomenon we suggest the possibility of viral enzyme induction, increased release of protease and thirdly that EBV carries a gene for synthesis of a collagenase.
 ...
PMID:[Enzyme induction by Epstein-Barr-virus-producing infection of lymphoblastoid cell lines]. 23 Apr 36

The BZLF1 or zta immediate-early gene of Epstein-Barr virus (EBV) encodes a 33-kilodalton phosphorylated nuclear protein that is a specific transcriptional activator of the EBV lytic cycle when introduced into latently infected B lymphocytes. We have shown previously that the divergent EBV DSL target promoter contains two zta-response regions, one within the minimal promoter and the other in an upstream lymphocyte-dependent enhancer region. In this study, we used footprinting and gel mobility retardation assays to reveal that bacterially synthesized Zta fusion proteins bound directly to six TGTGCAA-like motifs within DSL. Four of the Zta-binding sites lay adjacent to cellular TATA and CAAT factor-binding sites within the minimal promoter, and two mapped within the enhancer region. Single-copy oligonucleotides containing these Zta-binding sites conferred Zta responsiveness to heterologous promoters. In addition, the Zta protein, which possesses a similar basic domain to the conserved DNA-binding region of the c-Fos, c-Jun, GCN4, and CREB protein family, proved to bind directly to the consensus AP-1 site in the collagenase 12-O-tetradecanoylphorbol-13-acetate response element. Cotransfection with zta also trans activated a target reporter gene containing inserted wild-type 12-O-tetradecanoylphorbol-13-acetate response element oligonucleotides. Cellular AP-1 binding activity proved to be low in latently EBV-infected Raji cells but was induced (together with the Zta protein) after activation of the lytic cycle with 12-O-tetradecanoylphorbol-13-acetate. We conclude that EBV may have captured and modified a cellular gene encoding a c-jun-like DNA-binding protein during its evolutionary divergence from other herpesviruses and that this protein is used to specifically redirect transcriptional activity toward expression of EBV lytic-cycle genes in infected cells.
 ...
PMID:The zta transactivator involved in induction of lytic cycle gene expression in Epstein-Barr virus-infected lymphocytes binds to both AP-1 and ZRE sites in target promoter and enhancer regions. 215 99

The immunologic competence of human placental mononuclear cells was compared to that of adult and cord blood mononuclear cells. Mononuclear cells were isolated from fresh placentas by digestion with collagenase and DNase, followed by Ficoll-Hypaque and discontinuous Percoll separation. Placental cells incubated with phytohemagglutinin (PHA) synthesized significantly more interferon-gamma (IFN-gamma) at 2 days (29 +/- 5.5 IU/ml) and 5 days (46 +/- 8.5 IU/ml) than PHA-activated cord cells (3.6 +/- 0.6 IU/ml at 2 days and 2.7 +/- 0.7 IU/ml at 5 days) but less than PHA-activated adult cells (81 +/- 20 IU/ml at 2 days and 270 +/- 161 IU/ml at 5 days). Placental and adult cells, but not cord cells, also synthesized significant quantities of IFN-gamma following incubation with interleukin-2 (IL-2). There was synergism between IL-2 and PHA activation for IFN-gamma production for some cord samples. After a 5- to 7-day incubation with IL-2, the lymphocyte-activated killer (LAK cell) cytotoxicity of placental cells (measured in a 3-hr chromium-release assay at an E:T ratio of 40:1) was enhanced 13-fold against K562 target cells (6 +/- 2% to 77 +/- 4%) compared to a 4-fold increase in cord cells (16 +/- 4% to 68 +/- 3%) and a 2-fold increase in normal adult cells (35 +/- 4% to 65 +/- 3%. Against the natural killer (NK)-resistant Raji target, placental cells increased their LAK cytotoxic activity (3 +/- 1% to 59 +/- 7%) compared to a 7-fold increase with cord cells (6 +/- 1% to 43 +/- 3%) and a 3-fold increase with adult cells (11 +/- 2% to 38 +/- 4%). A notable degree of cytotoxic activity in the absence of IL-2 against Molt targets was noted in 11 of 14 (79%) placental cell samples at 5 days. Only 10 of 24 (42%) adult and 17 of 37 (40%) cord samples showed spontaneous cytotoxic activity equal to or greater than 10%. Some placental samples actually showed an increase in cytotoxic activity when incubated without IL-2. The ability of placental cells to produce significant levels of IFN-gamma, to develop considerable LAK activity, and to maintain or develop cytotoxic activity in the absence of IL-2 suggests a vigorous, active immune system of the placenta compared to the relatively dormant immune system of the neonate. These observations suggest that placental cells may have a primary role in fetal defense.
 ...
PMID:Enhanced interferon production and lymphokine-activated cytotoxicity of human placental cells. 313 Jan 92

Despite some functional impairment of the newborn's T-cell immune system, most infants survive the intrauterine and perinatal period without succumbing to infection or maternal lymphocyte engraftment. The placenta may play a crucial role in protecting the infant from microbial and histocompatibility antigens. Accordingly, we studied phenotypic and functional capacities of placental cells. Placentas were obtained from uncomplicated pregnancies. Matched cord blood and maternal peripheral blood were also obtained in many instances. Fresh minced placental tissue was washed and digested with collagenase and DNase and mononuclear cells were obtained by density gradient centrifugation. The average yield was 10(6) cells/g of tissue with greater than 80% viability. Chromosome analysis of five placental preparations indicated that these cells were of fetal rather than maternal origin. The isolated placental cells consisted of trophoblasts, lymphocytes (74 +/- 3%), monocytes (16 +/- 3%), and granulocytes (8 +/- 2%). E-rosette forming cells (T cells) made up 65 +/- 2% and surface membrane immunoglobulin positive cells made up 8 +/- 1% of the placental mononuclear cells. Fluorescent activated analysis of the mononuclear cells indicated less Leu 4-positive cells (Pan-T) 43 +/- 3%, and less Leu 3-positive (T-helper cells) (25 +/- 2%), than cord and maternal cell preparations. Leu-2, DR, and B1 positive cells were similar to those in cord and maternal blood. Leu 7 and especially Leu 11 positive cells, markers for natural killer cells, were abundant in placental cells, making up 4 +/- 0.7% and 20 +/- 3%, respectively. The Leu 7/Leu 11 ratio of the placental cells was different from either the maternal or cord blood cells. Natural killer activity of placental cells against a K562 natural killer target was low, despite the abundance of cells with NK markers. The K562 activity was low in the placental cells, similar to the low NK activity of maternal and cord cells. Molt 4f killer activity was near normal. Lectin-dependent cytotoxicity using an EL-4 cell target plus PHA was low in placentas, compared to normal, maternal, or cord cell cytotoxicity. Matched samples indicated that LDCC activity was mother greater than cord greater than placenta. Antibody-dependent cytotoxicity (Raji target) of placental cells showed low activity, and again the paired studies indicated that normal controls greater than maternal greater than cord greater than placenta cytotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Phenotypic and cytotoxic characteristics of the immune cells of the human placenta. 374 13

Viable mononuclear and epithelial cells were dispersed from human colonic tissue by treatment with collagenase and ethylene diamino-tetra acetate (EDTA) and separated by centrifugal elutriation. Using a single cell cytotoxic assay, functional endogenous and interferon responsive mononuclear cytotoxic cells were detected. Compared to peripheral blood lymphocyte associated killer cells that had been exposed to similar treatment, these colonic killer cells demonstrated lower efficiency cytotoxicity of Molt-4 target cells. Furthermore, inefficient, but interferon responsive cytotoxic cells were present which bound and lysed freshly isolated autologous epithelial cells. The cytotoxicity of these colonic mononuclear natural killer (NK) like cells appeared specific in that cells bound but did not lyse NK resistant Raji cells, even after interferon activation.
 ...
PMID:Isolation of spontaneous and interferon inducible natural killer like cells from human colonic mucosa: lysis of lymphoid and autologous epithelial target cells. 619 16

The effect of 11 anticancer drugs on the ability of Raji lymphoma cells to form colonies in soft agar was determined with the use of both a 1-hour and a continuous drug exposure. Three distinct patterns of drug sensitivities were observed: a) Dactinomycin, adriamycin, bleomycin, mitomycin C, vincristine, and cis-platinum II all produced a dose-dependent reduction in colony formation following a 1-hour exposure, which was further augmented by a continuous exposure to the drugs; b) the antimetabolites (methotrexate, beta-cytosine arabinoside, and 5-fluorouracil) and pentamethylmelamine had no suppressive effects on colony formation with a 1-hour exposure, but they produced marked cytotoxicity with continuous drug exposure; and c) L-phenylalanine mustard had the same degree of colony suppression with both a 1-hour and a continuous drug exposure. Preincubation of Raji cells with an enzyme mixture (DNase + pronase + collagenase) did not alter the degree of colony suppression observed with the anticancer drugs. These results indicate that continuous drug exposure should be compared to a 1-hour drug incubation to determine in vitro drug sensitivities of fresh human tumors in the soft agar clonogenic assay, because the 1-hour drug exposure may not identify certain drugs that are potentially clinically active.
 ...
PMID:Anticancer drugs: effect on the cloning of Raji lymphoma cells in soft agar. 694 21

We showed previously that human malignant non-Hodgkin's lymphomas (NHL) degrade extracellular matrix (ECM) components through the action of metalloproteinases and that elevated expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) correlated with a poor clinical outcome in patients with NHL. In the present study we sought to investigate whether there is any correlation between the expression of gelatinases (MMP-2 and MMP-9), TIMP-1, and the expression of cytokines and growth factors such as interleukin-1beta (IL-1beta), IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGFbeta), and basic fibroblast growth factor (bFGF) in human NHL. In lymphoma tissues obtained from 32 patients, elevated expression of IL-6 correlated significantly with elevated messenger RNA (mRNA) levels of MMP-9, MMP-2, and TIMP-1. Moreover, in human lymphoid cell lines of B- and T-cell origin (Raji, Jurkat, and NC-37), IL-6 stimulated production of MMP-9 and MMP-2 but not TIMP-1. In the Matrigel invasion assay IL-6 significantly upregulated transmigration of Raji and Jurkat cells, which in turn was inhibited by recombinant human TIMP-1 and anti-MMP-9 and MMP-2 antibodies. We postulate that IL-6 may play a role in the clinical aggressiveness of human NHL by stimulating MMP production.
 ...
PMID:Interleukin-6 regulation of matrix metalloproteinase (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression in malignant non-Hodgkin's lymphomas. 1047 38