Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new cell line (SARG) was established from a human radiation-induced osteosarcoma (OSA). It showed an epithelial-like morphology with polymorphous and sometimes bizarre nuclei. SARG had an osteoblastic differentiation pattern: almost 100% of the cells were positive for alkaline phosphatase, type I and III collagens and osteonectin. The expression of class I HLA antigens was detectable even after 40 in vitro passages. The expression of MHC antigens was greatly increased after in vitro treatment with interferon gamma (IFN-gamma), whereas interferon alpha (IFN-alpha) and tumor necrosis factor alpha (TNF-alpha) increased the expression of class I antigens, but not of class II antigens. SARG was tumorigenic after subcutaneous injection in nude mice. Experimental metastases were never detected.
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PMID:SARG: a new human osteosarcoma cell line. Expression of bone markers and of major histocompatibility antigens. 162 59

Recent studies have demonstrated homology between bone-derived growth factor and beta 2 microglobulin. We have shown that beta 2 microglobulin has proliferative actions on human bone-derived cells in vitro and that these cells also show immunogenicity for beta 2 microglobulin. beta 2 microglobulin stimulated the incorporation of 3H-thymidine into DNA of human bone cells in a dose-dependent manner. In contrast to this stimulatory action, beta 2 microglobulin had no detectable activity with the same concentration on the production of osteocalcin, alkaline phosphatase activity or prostaglandin E2 synthesis. The possibility that the human bone-derived cells could also produce beta 2 microglobulin was examined. Under basal conditions these cells exhibit immunoreactivity for beta 2 microglobulin, the expression of which could be enhanced following treatment with interferon gamma in a dose-dependent manner. The co-localization of staining for beta 2 microglobulin and alkaline phosphatase, a marker of the osteoblast phenotype, indicate that human osteoblast-like cells represent a source of activity of this factor. The production of beta 2 microglobulin by human osteoblast-like cells and the subsequent action of this factor on cells within the bone microenvironment may indicate a role for beta 2 microglobulin as a local regulator of bone metabolism.
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PMID:Immunoreactivity and proliferative actions of beta 2 microglobulin on human bone-derived cells in vitro. 190 70

The influence of recombinant human interferon alpha 2a (rIFN alpha), recombinant human interferon beta 1 (rIFN beta), and recombinant human interferon gamma (rIFN gamma) on human dermal microvascular endothelial cells (HDMEC) cultured in vitro was studied in various rIFN concentrations (0.1 IU/ml-10(4) IU/ml) over 2, 3, 4, 6, 8, and 10 d. Cell morphology and ultrastructure, cell proliferation, expression of class II alloantigens (HLA-DR and HLA-DQ), and intercellular adhesion molecule-1 (ICAM-1) were investigated using an in vitro technique established in our laboratory. All rIFN tested induced alterations of typical HDMEC morphology; the cells became spindle-shaped and fibroblastoid, although they maintained their endothelial cell marker expression. Also, all IFN dose- and time-dependently inhibited the proliferation of HDMEC in vitro (rIFN alpha greater than beta greater than gamma), whereby rIFN alpha exerted the strongest growth-inhibitory effect. Alkaline phosphatase anti-alkaline phosphatase (APAAP) immunocytochemistry of the cultured cells showed dose- and time-dependent stimulation of ICAM-1 and class II antigen expression only by rIFN gamma (HLA-DR greater than HLA-DQ), rIFN alpha and beta did not exert any immunomodulatory activity on HDMEC in vitro. These results indicate that HDMEC are an important target for the action of IFN. Besides growth inhibition, it seems that rIFN gamma in particular may be involved in the modulation of leucocyte adhesion and trafficking by altering the immunophenotype of the endothelial cell population.
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PMID:Effects of rIFN alpha, beta, and gamma on the morphology, proliferation, and cell surface antigen expression of human dermal microvascular endothelial cells in vitro. 197 80

Recent studies have suggested that interleukin-1 or tumor necrosis factor-stimulated bone resorption is mediated by osteoclast-activating factor elaborated by osteoblastic cells. Since recombinant interferon gamma inhibits stimulation of bone resorption by these cytokines, we examined here the effects of recombinant human interferon gamma (rhIFN-G) on DNA synthesis and alkaline phosphatase (ALP) activity of a human osteoblastic osteosarcoma cell line, SaOS2, under preconfluent culture conditions. Addition of rhIFN-G to the cells markedly inhibited their DNA synthesis and ALP activity in a dose-dependent fashion. However, the inhibition was not dependent on the culture time. The highest inhibitory effect was observed in 10% serum-containing culture medium. The inhibitory effect on DNA synthesis was not eliminated by addition of indomethacin, a cyclooxygenase inhibitor. Furthermore, combination of rhIFN-G and recombinant human tumor necrosis factor alpha inhibited their DNA synthesis and the ALP activity in synergistic fashion. Therefore, these data suggest that rhIFN-G is a potent inhibitor for human osteoblastic cells.
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PMID:[Inhibitory effect of recombinant human interferon gamma on human osteoblastic osteosarcoma cells (SaOS2)]. 251 49

To evaluate the effect of Qing-wen Granule (QWG) on immunological function, T lymphocyte subsets and interferon gamma(INF-gamma) expression cells in peripheral blood mononuclear cells, lymphocyte transformation rate and the level of salivary secretory IgA (sIgA) were determined by alkaline phosphatase antialkaline phosphatase (APAAP) technique or 3H-TdR incorporation with lymphocyte stimulation index(SI) or agar single immunodiffusion in infantile respiratory viral infection. The results showed that the percentage of CD3, CD4, and CD4/CD8 ratio of patients treated with QWG for 3 days were not significantly different in comparing with the control group untreated with QWG (P > 0.05), but the values of IFN-gamma expression cell, SI and the level of sIgA were more markedly increased than that of control (P < 0.05). It suggested that the QWG could improve and regulate immune function in infantile respiratory viral infection.
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PMID:[A study on effect of qingwen granule in regulating immunological function in infantile respiratory viral infection]. 758 61

We have investigated the effect of a number of cytokines on the human acute myelomonocytic leukemic cell line, ML-1. The differentiation inducing effects of interleukins (IL-1 beta, IL-3 and IL-6), colony stimulating factors (GCSF and GMCSF), TNF, LIF and IFNg, were studied either individually or in combination. Criteria for monocytic differentiation were as follows: an increase in the percentage of cells reducing nitroblue tetrazolium (NBT) salt, an increase in the alkaline phosphatase activity as well as the appearance of macrophagic phenotype. Among all the cytokines tested, only TNF was found to induce differentiation and to inhibit growth of ML-1 cells. IL-3, IL-6, interferon gamma, GCSF and to a smaller extent IL-1 beta and GMCSF synergized the differentiation inducing activity of TNF.
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PMID:Comparative analysis of the effects of recombinant cytokines on the growth and differentiation of ML-1, a human myelogenous leukemic cell line. 768 36

IP-10 is a member of the chemokine family of cytokines and is induced in a variety of cells in response to interferon gamma and lipopolysaccharide. The self-aggregation common to many chemokines, including IP-10, has hindered the identification of a specific IP-10 receptor. Using an IP-10 alkaline phosphatase fusion protein that fortuitously blocks this self-aggregation, we have identified an IP-10 binding site on a variety of cells including endothelial, epithelial, and hematopoietic cells. This binding site has a Kd of 25 nM, is inhibited by recombinant murine or human IP-10, and is dependent on the presence of cell surface heparan sulfate proteoglycans (HSPG). This conclusion is based on the findings that IP-10 binding to cells is: (a) inhibited by heparin and heparan sulfate; (b) sensitive to a 1 M NaCl wash; (c) eliminated by treatment with heparinase and trypsin; and (d) absent on mutant CHO cells that do not express cell surface HSPG. Platelet factor 4 (PF4), but not IL-8, monocyte chemoattractant protein-1, RANTES, monocyte inflammatory protein (MIP)-1 alpha, or MIP-1 beta, can compete effectively with IP-10 for binding to the cell surface. Furthermore, IP-10 shares with PF4 the ability to inhibit endothelial cell proliferation (IC50 = 150 nM). These studies demonstrate specificity in the interaction of chemokines and HSPG, and they define IP-10 and PF4 as a distinct subset of chemokines sharing an HSPG-binding site and angiostatic properties.
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PMID:The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation. 779 Aug 18

We adopted the nonradioactive method used for blot hybridization for the detection of inducible mRNA for HLA-DR alpha by the in situ hybridization. Unstimulated and interferon gamma stimulated MonoMac6 and U937 human monocytic cell lines were used as target cells. Sulphonation of plasmid pBR322 with HLA-DR alpha cDNA insert (2 x 700 bp, in Pstl restriction site) was performed according to the manufacturer's procedure (SulfoProbe Kit, Sigma). The hybridization signals were detected with mouse monoclonal, anti-sulphonated DNA antibody, followed by immunovisualization with anti-mouse IgG-alkaline phosphatase conjugates. Unstimulated MonoMac6 and U937 cells showed few granular reaction products only in small percentage of cells (1-5%), while in IFN gamma stimulated cells the fine granular immunoenzymatic reaction was observed in the cytoplasm of majority of cells (> 80%). This method seems to be easy and rapid to perform, making it applicable for routine diagnostic purposes in tissue sections and biopsies.
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PMID:Detection, by in situ hybridization using sulphonated cDNA probe, the specific mRNA for HLA-DR alpha induced in monocyte cell lines by recombinant interferon gamma. 823 22

Lymphocytes are implicated in the pathogenesis of bone disease in chronic inflammation, osteoporosis, transplantation and osteopetrosis. The effects of lymphocytes and lymphocyte-conditioned medium on bone-resorbing activity and osteoclast function have been well studied, but there are few studies of the effects of LCM on bone formation and osteoblast function. The effects of LCM on the function of the MG-63 human osteosarcoma cell line were studied, which, when stimulated with 1,25-(OH)2D3, demonstrates many of the properties of the mature human osteoblast. Lymphocytes contain oestrogen receptors and the model was also used to test the hypothesis that the effects of oestrogen on bone cells may be mediated indirectly via lymphokines. Lymphokines were measured by ELISA in human lymphocyte conditioned medium (LCM) collected following incubation of mixed lymphocytes with or without stimulation for 72 h. Unstimulated LCM increased proliferation of MG-63 cells and this increase was not affected by neutralization of interleukin 1 (IL-1), IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF), lymphotoxin alpha, or interferon gamma (IFN-gamma). Phytohaemagglutinin-stimulated LCM decreased proliferation of MG-63 cells, as well as induced expression of IL-6 mRNA, increased alkaline phosphatase production, and inhibited osteocalcin production. The decrease in proliferation was abolished by neutralization of IFN-gamma but was unaffected by neutralization of IL-1, IL-2, IL-3, IL-4, IL-6, GM-CSF, TNF, or lymphotoxin alpha. Neutralization of IFN-gamma in stimulated LCM also partially inhibited the increase in alkaline phosphatase production but had no effects on the decrease in osteocalcin production. Although oestrogen inhibited lymphocyte proliferation, the effects of LCM collected from lymphocytes in the presence of oestrogen on MG-63 cell proliferation and function was no different than the effects of LCM collected in the absence of oestrogen. LCM has multiple effects on MG-63 cell function and gene expression. Lymphocyte stimulation during the preparation of LCM further modulates these effects. Although partially mediated by IFN-gamma, the effects of LCM on these cells cannot be completely explained by individual component lymphokines. This may have implications for understanding the pathophysiology of bone loss in inflammatory disorders as well as possible feedback loops of locally generated cytokines in bone.
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PMID:Effects of human lymphocyte-conditioned medium on MG-63 human osteosarcoma cell function. 972 33

Radiation of the esophagus of C3H/HeNsd mice with 35 or 37 Gy of 6 MV X rays induces significantly increased RNA transcription for interleukin 1 (Il1), tumor necrosis factor alpha (Tnf), interferon gamma inducing factor (Ifngr), and interferon gamma (Ifng). These elevations are associated with DNA damage that is detectable by a comet assay of explanted esophageal cells, apoptosis of the esophageal basal lining layer cells in situ, and micro-ulceration leading to dehydration and death. The histopathology and time sequence of events are comparable to the esophagitis in humans that is associated with chemoradiotherapy of non-small cell lung carcinoma (NSCLC). Intraesophageal injection of clinical-grade manganese superoxide dismutase-plasmid/liposome (SOD2-PL) 24 h prior to irradiation produced an increase in SOD2 biochemical activity in explanted esophagus. An equivalent therapeutic plasmid weight of 10 microgram ALP plasmid in the same 500 microliter of liposomes, correlated to around 52-60% of alkaline phosphatase-positive cells in the squamous layer of the esophagus at 24 h. Administration of SOD2-PL prior to irradiation mediated a significant decrease in induction of cytokine mRNA by radiation and decreased apoptosis of squamous lining cells, micro-ulceration, and esophagitis. Groups of mice receiving 35 or 37 Gy esophageal irradiation by a technique protecting the lungs and treating only the central mediastinal area were followed to assess the long-term effects of radiation. SOD2-PL-treated irradiated mice demonstrated a significant decrease in esophageal wall thickness at day 100 compared to irradiated controls. Mice with orthotopic thoracic tumors composed of 32D-v-abl cells that received intraesophageal SOD2-PL treatment showed transgenic mRNA in the esophagus at 24 h, but no detectable human SOD2 transgene mRNA in explanted tumors by nested RT-PCR. These data provide support for translation of this strategy of SOD2-PL gene therapy to studies leading to a clinical trial in fractionated irradiation to decrease the acute and chronic side effects of radiation-induced damage to the esophagus.
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PMID:Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmid/liposome (SOD2-PL) gene therapy. 1112 Dec 10


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