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)

We examined the effect of tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) and IL-6 on alkaline phosphatase (ALP) and osteocalcin (OC) production, calcification and calcium (Ca) release in human cultured osteoblastic cells established from human periosteum. The cells were cultured with varying concentrations of cytokines for three days. TNF-alpha and IL-1 beta significantly inhibited ALP production, decreased cellular Ca content, and significantly enhanced 45Ca release in human osteoblastic cells. IL-6, on the other hand, significantly suppressed 45Ca release from the osteoblastic cells. Any one of these cytokines did not influence the production of OC by the osteoblastic cells. The results obtained suggest that TNF-alpha and IL-1 beta may inhibit bone formation and calcification and promote bone resorption, while the effects of IL-6 on osteoblastic cells may be a little different from those of TNF-alpha or IL-1 beta. Cytokine-dependent these effects on the osteoblastic cells may be one of the mechanisms by which bone loss occurs in patients with rheumatoid arthritis.
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PMID:[Inhibitory effects of cytokines on human osteoblastic cells]. 802 Aug 64

IL-6 is a 26-kDa protein cytokine with pleiotropic activities in both hematopoietic and immune systems. It is one of the major mediators of the acute phase inflammatory response. Recently it has been demonstrated that pharmacological doses of human recombinant IL-6 (rhIL-6) inhibit certain murine tumors as well as stimulate thrombopoiesis in mice, dogs, nonhuman primates, and humans. The purpose of our study was to evaluate the effects and toxicity of rhIL-6 administration in nonhuman primates with particular reference to subject age. We treated 10 female monkeys of two age groups (midle-aged and old) with rhIL-6 (15 micrograms/kg/day) for 28 days. The monkeys were observed to be somewhat lethargic and lost an average of 10% of their body weights. The white blood cell count rose transiently whereas the levels of hemoglobin and hematocrit fell significantly and remained depressed for the same period. Importantly, platelet count rose and remained elevated for the duration of treatments. Serum alkaline phosphatase levels increase significantly and certain parameters of clinical immune competence were altered by IL-6 treatment. Treatment effects were similar in both age groups, but the changes in immune functions were different between the midle-aged and old monkeys. We observed a pattern in which the middle-aged group had a significant decrease in immune functions as a result of IL-6 administration and recovered to pretreatment level despite continuous treatment, whereas the old monkeys had a more protracted but less significant decline in these same immune functions during the trial.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of recombinant human interleukin-6 on blood and immune parameters in middle-aged and old rhesus monkeys. 812 61

We examined the effect of TNF-alpha, IL-1 beta and IL-6 on alkaline phosphatase (ALP) and osteocalcin (OC) production, calcification and calcium (Ca) release in human osteoblastic cell cultures obtained from human periosteum. The cells were cultured with varying concentrations of cytokines for 3 days. TNF-alpha and IL-1 beta significantly inhibited ALP production, decreased cellular Ca content, and significantly enhanced 45Ca release in human osteoblastic cells. IL-6, on the other hand, significantly suppressed 45Ca release by osteoblastic cells. These cytokines did not influence the production of OC by osteoblastic cells. The results obtained suggest that TNF-alpha and IL-1 beta may inhibit bone formation and calcification and that the effects of IL-6 on osteoblastic cells may be different from those of TNF-alpha or IL-1 beta. These effects on osteoblastic cells may be one of the mechanisms by which bone loss occurs in patients with RA.
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PMID:Effects of cytokines on alkaline phosphatase and osteocalcin production, calcification and calcium release by human osteoblastic cells. 815 83

The effects of interleukin-11(IL-11) on the differentiation of osteoblast precursors was tested using a bone nodule forming assay in rat calvaria cell cultures. IL-11 caused a dose dependent inhibition of nodule formation, with 500 U/ml IL-11 resulting in complete inhibition of nodule formation. IL-11 also caused a reduction in alkaline phosphatase expression in these cultures. These effects are similar to, but more potent than, the actions of IL-6 on these cells. These results indicate that IL-11 is an osteotropic cytokine and suggest that IL-11 may be an important inhibitor of bone formation in health and disease.
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PMID:Interleukin-11 inhibits bone formation in vitro. 828 26

A novel long-term cultured interleukin (IL)-3-dependent human myelodysplastic cell line, MDS92, was shown to contain several myeloid-lineage cells such as neutrophils, macrophages, eosinophils, and a small number of megakaryocyte-lineage cells. Therefore this cell line possesses at least bipotential characteristics of myeloid- and megakaryocyte-lineages. Granulocyte colony-stimulating factor clearly promoted the neutrophil alkaline phosphatase activity of MDS92 cells. To the contrary, the incidence and growth of CD41-positive cells were hardly affected by the addition of IL-6, IL-11, c-mpl ligand (thrombopoietin, TPO) or erythropoietin. TPO slightly supported the growth of CD34-positive cell fraction, but not CD41-positive cell fraction of MDS92 cells in combination with IL-3 or Steel factor. This cell line will be a useful tool for the study of MDS stem cells, but the mechanism of commitment of differentiation in MDS stem cells remains unknown.
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PMID:A novel factor-dependent human myelodysplastic cell line, MDS92, contains haemopoietic cells of several lineages. 854 20

The ob gene product, leptin, is an important circulating signal for the regulation of body weight. To identify high affinity leptin-binding sites, we generated a series of leptin-alkaline phosphatase (AP) fusion proteins as well as [125I]leptin. After a binding survey of cell lines and tissues, we identified leptin-binding sites in the mouse choroid plexus. A cDNA expression library was prepared from mouse choroid plexus and screened with a leptin-AP fusion protein to identify a leptin receptor (OB-R). OB-R is a single membrane-spanning receptor most related to the gp130 signal-transducing component of the IL-6 receptor, the G-CSF receptor, and the LIF receptor. OB-R mRNA is expressed not only in choroid plexus, but also in several other tissues, including hypothalamus. Genetic mapping of the gene encoding OB-R shows that it is within the 5.1 cM interval of mouse chromosome 4 that contains the db locus.
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PMID:Identification and expression cloning of a leptin receptor, OB-R. 1505 99

To investigate the pathogenesis of accelerated bone formation in estrogen deficiency, diffusion chambers containing osteoblast-like cells isolated from newborn rat calvariae were transplanted into the peritoneal cavity of sham-operated (sham), ovariectomized (OVX) rats, and OVX rats with supplement of 17 beta-estradiol (OVX + E2). Bone formation in the diffusion chambers transplanted into OVX rats was more accelerated than that transplanted into sham rats and OVX + E2 rats. Osteoblast-like cells cultured with the sera isolated from OVX rats exhibited higher levels of the DNA content in the culture wells, alkaline phosphatase activity, messenger RNA expression for alkaline phosphatase and osteocalcin, calcium content in the cell layer, and formation of bone-like nodules than those exposed to the sera from sham rats and OVX + E2 rats. Antibody against IGF-I almost completely inhibited the increase in DNA contents induced by the sera isolated from OVX rats but partially inhibited alkaline phosphatase activity. Adding IGF-I to the sera isolated from sham rats increased the DNA content to the same extent as that induced by the supplement with the sera from OVX rats but did not increase alkaline phosphatase activity appreciably. Addition of various concentrations of 17 beta-estradiol, interleukin (IL)-1, and IL-6 to the sera isolated from sham rats did not increase the DNA content or alkaline phosphatase activity in the osteoblast-like cells. These results indicate that some systemic factor(s) other than IGF-I, IL-1, and IL-6 may be responsible for the stimulative effect on osteoblast differentiation in the pathogenesis of the accelerated bone formation induced by estrogen deficiency in rats.
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PMID:An estrogen deficiency caused by ovariectomy increases plasma levels of systemic factors that stimulate proliferation and differentiation of osteoblasts in rats. 859 91

We have established a human stromal cell line derived from the bone marrow of a patient with chronic myelogenous leukemia in blast crisis. This cell line, designated FS-1, exhibits a fibroblastoid morphology and does not express any hematopoietic cell marker tested. FS-1 is negative for alpha-naphthyl acetate esterase, acetylated LDL, von Willebrand factor, and shows no phagocytosis. This cell line is positive for acid phosphatase, alkaline phosphatase, collagen types I, III, IV, and fibronectin. cDNA from FS-1 cells was subjected to amplification by the polymerase chain reaction to assess the constitutive expression of several cytokine genes. Transcripts for interleukin (IL)-6, IL-7, macrophage colony-stimulating factor (M-CSF), and stem cell factor (SCF) were detected in FS-1 cells. IL-6 and SCF also were detected in the culture supernatants of FS-1 at a concentration of 95 pg/ml and 21.2 pg/ml, respectively. These data show that FS-1, established from a human bone marrow, is a stromal cell line which was not generated using transfection with SV40 T antigen. FS-1 cells may be useful in supporting human hematopoietic cells for experimental manipulation.
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PMID:Establishment and characterization of a novel human bone marrow stromal cell line, FS-1. 872 43

Osteoclasts (OCs), which form by fusion of hematopoietic precursor cells, are typically present in large numbers in giant cell tumors of bone (GCTBs). These tumors may, therefore, contain cells which secrete factors that stimulate recruitment and differentiation of OC precursors. Multinucleated cells resembling OCs also form in cultures of human cord blood monocytes (CBMs) stimulated by 1.25 dihydroxyvitamin D3, but these cells lack the ability to form bone resorption pits, the defining functional characteristic of mature OCs. CBMs may thus require additional stimulation to form OCs; we therefore investigated whether GCTBs are a source of such a stimulus. CBMs were stimulated in long term (21 day) culture by medium conditioned by explants of GCTBs; media collected within 15 days of explant (early-CM) and after 15 days (late-CM) were employed. We also cocultured CBMs with primary GCTB-derived stromal cells as well as immortalized bone marrow stroma-derived cells. CBMs stimulated by early-CM formed resorption pits on cortical bone slices; however, stimulation by late-CM resulted in virtually no resorption. Both early-CM and late-CM increased CBM proliferation, but not the proportion of vitronectin receptor positive or multinucleated cells. Coculture of CBMs with stromal cells of GCTBs or bone marrow did not result in bone resorption, although these stromal cells (most expressing alkaline phosphatase but progressively losing parathyroid hormone receptor expression) expressed mRNA for cytokines involved in OC differentiation, including macrophage-CSF, granulocyte-macrophage-CSF, IL-11, IL-6, and stem cell factor. Our results indicate that CBMs are capable of terminal OC differentiation in vitro, a process requiring 1,25 dihydroxyvitamin D3 as well as diffusible factor(s) which can be derived from GCTB. Stromal cells of GCTB may produce such factors in vivo, but do not support OC differentiation in vitro, possibly through phenotypic instability in culture.
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PMID:Human cord blood monocytes undergo terminal osteoclast differentiation in vitro in the presence of culture medium conditioned by giant cell tumor of bone. 881 3

The synthetic polynucleotide polyadenylic-polyuridylic acid (polyA:polyU) has shown antitumor activity in murine studies and human breast cancer. PolyA:polyU was evaluated in 25 cancer patients receiving weekly intravenous doses between 3 and 600 mg/m2. PolyA:polyU was well tolerated up to 600 mg/m2, with no doselimiting toxicity (all < grade 3). Side effects included mild elevation in temperature, fatigue, and mild hyperglycemia. No changes outside of the normal range in hematocrit, WBC count, platelet count, total bilirubin, or alkaline phosphatase were observed. Of 25 patients, 18 completed at least one cycle of 6 weeks, and 5 completed two cycles (median 6 weeks). Four patients had stable disease over 11-13 weeks of treatment, and no clinical responses were observed. At 24 h after the first treatment, there were no significant increases in biologic response (beta 2-microglobulin and neopterin in serum, or 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells). A small increase in beta 2-microglobulin was observed 24 h after the week 3 treatment (1.1-fold, p < 0.01). By the third week of treatment, 2-5A synthetase levels decreased slightly (to 80% of baseline, p < 0.01). No changes in cytokines IL-6, IL-12, tumor necrosis factor (TNF), or IL-2 receptor in serum were detected after 24 h of treatment. Thus, at these doses, polyA:polyU had no marked modulation on biologic responses in vivo, although this preparation significantly induced 2-5A synthetase in peripheral blood mononuclear cells in vitro. PolyA:polyU was well tolerated. An MTD was not reached but was greater than 600 mg/m2 on this weekly schedule.
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PMID:Phase I/IB study of polyadenylic-polyuridylic acid in patients with advanced malignancies: clinical and biologic effects. 887 34


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