Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF], granulocyte [G]-CSF, interleukin (IL)-1, IL-3, IL-5, IL-6, and macrophage [M]-CSF) on differentiation and functional activity of human eosinophilic HL-60 cells (Eos-HL-60) and compared them with effects on parental HL-60 promyelocytic leukemia cells. Purified biosynthetic GM-CSF and IL-5 enhanced cell proliferation and induced eosinophilic differentiation in the eosinophilic subline in both liquid and agar cultures. IL-3 and IL-6 stimulated cell proliferation but had no effect on cell differentiation, whereas IL-1 and G-CSF affected neither differentiation nor proliferation of Eos-HL-60 cells under the conditions tested. GM-CSF-, IL-3-, and IL-5-treated Eos-HL-60 cells showed increased O2- production in response to phorbol esters (PMA), enhanced phagocytosis of Candida albicans, and release of the enzymes arylsulfatase, beta-glucuronidase and eosinophil peroxidase (EPO). The degranulation of eosinophils induced by GM-CSF, IL-5, and IL-3 may have relevance to the potential clinical toxicity of these hematopoietins, which also stimulate eosinophilopoiesis. G-CSF had no effect on enzyme release, oxidative metabolism, or phagocytic capacity of Eos-HL-60 cells. IL-5 did not affect proliferation, differentiation, or enzyme release in promyelocytic HL-60 cells. These results indicate the specificity of IL-5 for the eosinophil lineage, confirm the effects of GM-CSF and IL-3 on eosinophilopoiesis and mature eosinophil function in a model system, and indicate the absence of G-CSF and IL-1 stimulation of eosinophils. The Eos-HL-60 line is a useful model for studying human eosinophil responses to cytokines.
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PMID:Differentiation and functional activity of human eosinophilic cells from an eosinophil HL-60 subline: response to recombinant hematopoietic growth factors. 137 88

Recent evidence confirms that cytokines such as IL-1, IL-4, IL-5, and GM-CSF may enhance or inhibit eosinophil function. Functions that are susceptible to modulation include eosinophil-mediated antibody-dependent damage of helminthic parasites, oxidative metabolism and degranulation. We have employed IgG and IgE-coated Sepharose beads to investigate selective modulation of IgG and IgE-mediated enzyme release by IL-1 beta. Both IgG and IgE-coated beads induced release of granular enzymes beta-glucuronidase and arylsulfatase. Enzyme release from IgG-stimulated eosinophils was inhibited by preincubation with IL-1 beta (100 pg/ml, P less than or equal to 0.05). In contrast, enzyme release by IgE-stimulated eosinophils was enhanced by IL-1 beta (100 pg/ml, P less than or equal to 0.05). These studies support the hypothesis that IL-1 beta has specific selective actions on eosinophil function. Furthermore, these actions on particle-stimulated enzyme release suggest that IgG and IgE mediated processes in eosinophils are differentially regulated.
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PMID:Selective regulation of eosinophil degranulation by interleukin 1 beta. 174 16

Bone resorption plays an important role in bone modeling and remodeling. Osteoclasts are the cells responsible for the bone resorption. Osteoclasts are located on endosteal bone surfaces and on the periosteal surface beneath the periosteum. They are multinucleated giant cells highly polarized in their morphology and function. Among the proximal surface, the membrane and the area of the cytoplasm directly oppose to the bone surface, which are specialized into two regions. A central region consisting of many irregular cytoplasmic processes and infoldings, the ruffled border, is known to be the active site of bone resorption. Surrounding the ruffled border, a second region, the clear zone provides an area of close attachment to the mineralized bone surface. The osteoclasts secrete a large amount of protons by the action of H(+)-pump on the ruffled border into the sealed resorption cavity, resulting in the acidified microenvironment under which condition the bone matrix is dissolved. Protons are provided by the intracellular action of carbonic anhydrase. Following the secretion of the protons, several ion-transporting systems, i.e., carbonate-chloride exchanger, chloride-channel, Ca(2+)-transport systems, Na+/K(+)-ATPase, and voltage-dependent Ca(2+)-channel, are sequentially operated on both apical and basolateral cytoplasmic membranes. In addition, osteoclasts contain a large amount of lysosomal enzymes (cathepsin C, beta-glycerophosphatase, beta-glucuronidase, etc.), which contribute to degrade the bone organic matrices exposed in the resorption cavity. These enzymes bind to the mannose-6-phosphate receptor on Golgi apparatus, are transported to the ruffled border and are secreted into the extracellular compartment in an exocytotic manner. Osteoclasts also have a high tartrate-resistant acid phosphatase activity which is currently used as a marker enzyme osteoclastic differentiation. Osteoclasts are considered to develop from hematopoietic stem cells. So far, the following four different pathways of the differentiation of osteoclast are proposed: The precursors of osteoclast develop (1) from multilineage hematopoietic cells via a completely separate differentiation line, (2) from granulocyte macrophage-colony forming cells, (3) from committed but proliferative monocyte-macrophage, and (4) from mature and unproliferative monocyte-macrophage. However, the differentiation line of the osteoclasts has still to be elucidated. The formation of osteoclasts as well as that of other hematopoietic cells is strongly regulated by many cytokines [interleukin (IL)-1,IL-3,IL-6, M-colony stimulating factor (CSF), and GM-CSF]. 1,25-Dihydroxyvitamin D3 and parathyroid hormone also stimulate the differentiation of osteoclast precursors. However, the mature osteoclasts do not possess the receptors for these hormones.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Osteoclasts in bone metabolism]. 175 56

Previously, we have shown that Escherichia coli alpha-hemolysin represents a potent stimulus for inflammatory mediator release (O2- release, beta-glucuronidase release, and leukotriene generation) from human polymorphonuclear granulocytes (PMN) as well as for histamine release from a human lymphocyte-monocyte-basophil cell suspension (LMB). In contrast, the E. coli alpha-hemolysin leads to a downregulation of cytokine release (interleukin 6 [IL-6], tumor necrosis factor alpha, and IL-1 beta) from human LMB. This study was undertaken (i) to analyze the priming efficacy of growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF] and granulocyte CSF [G-CSF]) on inflammatory mediator release from human PMN and LMB challenged with hemolysin-producing E. coli bacteria as well as with cell-free E. coli alpha-hemolysin and (ii) to identify major components involved in GM-CSF and G-CSF priming. GM-CSF pretreatment led to an increased chemiluminescence response from human PMN by up to 100%, leukotriene B4 generation was enhanced up to fivefold, and histamine release from human LMB increased from 45% +/- 15% to 75% +/- 5% (mean +/- standard distribution) of the total histamine content. G-CSF priming induced an increase in the chemiluminescence response by up to 50% +/- 5% from human PMN and an increase in histamine release from human LMB by 20% +/- 5%. The growth factors, GM-CSF and G-CSF, modulated neither beta-glucuronidase release from human PMN nor IL-8 release from human PMN and LMB challenged with the E. coli alpha-hemolysin. GM-CSF and G-CSF pretreatment increased the fluoride (NaF)-induced chemiluminescence response by up to 10-fold; the serine/threonine phosphatase inhibitor okadaic acid inhibited GM-CSF- and G-CSF-induced priming. NaF-induced histamine release was enhanced up to 60 and 30% by GM-CSF and G-CSF priming, respectively. GM-CSF and G-CSF pretreatment did not modulate phorbol 12-myristate 13-acetate-induced chemiluminescence response or histamine release. GM-CSF by itself induced an increase in 5-lipoxygenase-specific mRNA expression within 5 min. Our results indicate that (i) GM-CSF and G-CSF interact with inflammatory cells via distinct cellular signalling, (ii) the signal transduction pathway is dependent on the cellular mediator, and (iii) the use of growth factors may be a potent tool to influence the clinical outcome in infectious diseases.
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PMID:Effect of growth factors on Escherichia coli alpha-hemolysin-induced mediator release from human inflammatory cells: involvement of the signal transduction pathway. 751 12

Downregulation of MHC class I molecules is believed to be often the cause of tumor immune escape and at the same time it is the major obstacle to T-cell based immunotherapy of tumors. In our experimental model, the C57BL/6 mice bearing tumors induced by TC-1/A9 cells characterized by expression of HPV16 oncogenes and downregulation of H-2b molecules were immunized with highly immunogenic E7GGG.GUS DNA vaccine expressing the fused gene of modified HPV16 E7 (E7GGG) with E.coli beta-glucuronidase (GUS). The DNA vaccine was administered by gene gun on days 7 and 14 after s.c. injection of tumor cells. The tumors in situ were injected with recombinant vaccinia virus MVA expressing the gene for murine granulocyte-macrophage colony-stimulating factor (MVA-GM-CSF). Two doses of the DNA vaccine combined with at least two consecutive local treatments with MVA-GM-CSF were able to inhibit significantly the growth of tumors. We have shown by ELISPOT-IFNgamma that in situ expression of the GM-CSF gene did not enhance the E7 specific systemic Tcell response. We found that local injections of MVA-GM-CSF induced an increase of intratumoral CD3+ T cell counts and that the DNA vaccination resulted in up-regulation of MHC type I molecules on tumor cells in vivo. We suppose that i.t. delivery of MVA-GM-CSF changed the local tumor microenvironment and rendered tumors more attractive and better accessible to effector T cells.
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PMID:Combination of intratumoral injections of vaccinia virus MVA expressing GM-CSF and immunization with DNA vaccine prolongs the survival of mice bearing HPV16 induced tumors with downregulated expression of MHC class I molecules. 1782 23