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

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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)

Osteoblasts play a pivotal role during the bioresponse of bone to agents that stimulate bone resorption and/or inhibit bone formation including hormones, polypeptide growth factors, and cytokines. We examined the cytokines interleukin-1-beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) for their effects on osteoblastic proliferation and development and expression of alkaline phosphate and the osteoblast-specific protein osteocalcin in a mineralizing environment. Primary rat osteoblast-like cells (ROB) and osteoblastic cell lines derived from rat (ROS 17/2.8) and human (MG-63) osteosarcomas were studied. IL-1 beta and TNF-alpha were chosen because of their critical importance during the host response to local inflammatory stimuli. Qualitatively similar two- to threefold inhibition of osteocalcin synthesis by IL-1 beta and TNF-alpha were observed in all three postconfluent bone-forming model systems. Because of the readily measurable concentrations of osteocalcin produced in our culture protocol, it was not necessary to enhance osteoblastic synthesis of osteocalcin by supplementation with 1,25(OH)2-vitamin D3, a treatment which exerts pleiotropic effects on osteoblasts. Under the constraints of our protocol, where alkaline phosphatase and mineralization were already elevated at the 14-day onset of treatment, neither of these phenotypic properties was sensitive to a three-day cytokine exposure. Differences were noted in proliferation, where only TNF-alpha stimulated DNA synthesis in ROB cells, while both cytokines stimulated MG-63 cells. IL-1 beta and TNF-alpha failed to alter ROS 17/2.8 DNA synthesis except at the highest doses (25 pM IL-1 beta and 1 nM TNF-alpha) where inhibition was observed. These results further support the view that cytokine-mediated osteoblastic regulation can be relatively selective.
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PMID:Effects of interleukin-1 beta and tumor necrosis factor-alpha on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro. 145 94

Cytokine mRNA production in the thyroid tissues of patients with various thyroid diseases was analysed by in situ hybridization. In addition, infiltrating leukocytes were characterized by immunohistologic studies using the alkaline phosphatase anti-alkaline phosphatase (APAAP) staining technique. The following clinical material was investigated: two cases of Graves' disease, one with high and the other with a low amount of infiltrating leukocytes as well as two cases of non-toxic goitre also showing considerable quantities of infiltrating cells. The hybridization was performed on tissue sections with antisense probes for interferon-gamma (IFN-gamma), IFN-alpha E, IFN-beta, interleukin-6 (IL-6) and IL-1 beta. A small number of individual cells were found to express high levels of mRNA for IFN-gamma, IL-1 beta and measurable amounts of IL-6 throughout the tissue sections. However, IFN-alpha E or IFN-beta were not detected. Cytokine expressing cells were noted in the tissue of one patient with Graves' disease and in two cases with non-toxic goitre. In these samples a high amount of infiltrating leukocytes (CD45+) was detected, especially CD3+, CD8+, CD4+ and CD45RA+ T cells, in addition to B cells and macrophages. In one case an unusually large amount of T cell receptor gamma/delta+ (TcR gamma/delta+) cells was found. However, one sample of thyroid tissue derived from a patient with Graves' disease was poorly infiltrated and showed few cells expressing cytokines. In conclusion, using thyroid tissue as an example, our data suggest that the application of in situ hybridization with antisense RNA permits the study of cytokine production in tissues of both autoimmune and non-autoimmune origin.
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PMID:In situ hybridization of the mRNA for interferon-gamma, interferon-alpha E, interferon-beta, interleukin-1 beta and interleukin-6 and characterization of infiltrating cells in thyroid tissues. 153 76

The present study shows the effect of interleukin-1 beta (IL-1 beta) on some gene expressions and functions of fibroblastic cells (HPLF) derived from human periodontal ligament. HPLF were used at passages number 5 to 10. IL-1 beta increased DNA synthesis in both a dose- and an incubation time-dependent manner. IL-1 beta in combination with tumor-necrosis factor alpha or transforming growth factor beta synergistically stimulated the DNA synthesis in the cells. Since many studies have shown that the c-myc oncogene is involved in cell proliferation and differentiation, the effect of IL-1 beta on c-myc messenger RNA (mRNA) level in HPLF was examined. IL-1 beta induced a marked c-myc mRNA level in the cells at 90 minutes after initiation of the cytokine treatment. On the other hand, IL-1 beta significantly inhibited alkaline phosphatase (ALP) activity of the cells in a dose-dependent manner. Also an inhibitory effect was observed on the liver/bone/kidney ALP mRNA level of the cells, and this inhibition by IL-1 beta was dose- and incubation time-dependent. These results suggest that IL-1 beta is a regulatory cytokine involved in the regeneration of the human periodontal ligament.
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PMID:Effect of interleukin-1 beta on gene expressions and functions of fibroblastic cells derived from human periodontal ligament. 164 Mar 47

To examine the possible involvement of IL-6 in bone metabolism, a mouse osteoblastic cell line (MC3T3-E1) and primary osteoblast-like cells from fetal mouse calvaria were cultured with several systemic and local bone-resorbing agents and their expression of IL-6 mRNA was determined. Local bone-resorbing agents such as IL-1 alpha, IL-1 beta, TNF-alpha, and LPS greatly induced IL-6 mRNA expression in both MC3T3-E1 cells and primary osteoblast-like cells. Parathyroid hormone slightly increased expression of IL-6 mRNA in primary osteoblast-like cells but not in MC3T3-E1 cells. Neither IL-6 nor 1 alpha,25-dihydroxyvitamin D3 increased expression of IL-6 mRNA in either of the osteoblast-like cells. In agreement with the expression of IL-6 mRNA, biologically active IL-6 was produced in response to the treatment with IL-1 alpha, TNF-alpha, and LPS in MC3T3-E1 cells. Adding IL-6 dose dependently stimulated the release of 45Ca from prelabeled fetal mouse calvaria. Simultaneously adding suboptimal concentrations of IL-6 and IL-1 alpha induced bone resorption cooperatively. In accord with the increase in the release of 45Ca by IL-6, there were three times as many osteoclasts in the bone sections of calvaria cultured with IL-6 for 5 days as in the controls. IL-6 slightly suppressed alkaline phosphatase activity and collagen synthesis in MC3T3-E1 cells. These results indicate that IL-6 is also produced by osteoblasts, preferentially in response to local bone-resorbing agents, and it induces bone resorption both alone and in concert with other bone-resorbing agents.
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PMID:IL-6 is produced by osteoblasts and induces bone resorption. 212 24

Proximal tubular (PT) epithelial cells express MHC class II (Ia) antigens in immunologically-mediated renal injury. To study the role of PT as accessory cells, we generated several murine PT-like epithelial cell lines by transformation with origin-defective SV40 DNA. These transformed cell lines display typical alkaline phosphatase and gamma-glutamyl-transpeptidase enzyme activity, proliferation to epidermal growth factor (EGF) and sodium-dependent glucose uptake. Clonal lines of transformed tubular cells from both normal C3H/FeJ and autoimmune MRL-lpr mice do not constitutively express Ia antigens or mRNA for class II. However, stimulation with recombinant interferon-gamma(rIFN-gamma) induces Ia mRNA and surface product in the cell lines. These Ia-positive cells can process and present hen egg-white lysozyme (HEL) to antigen-specific Iak-restricted T cell hybrids. Unstimulated tubular cells do not express detectable IL-1 alpha, IL-1 beta, TNA-alpha, or IL-6 mRNA. However, stimulation with IL-1 alpha or LPS induces TNF-alpha transcripts. We conclude that these cell lines have characteristics most consistent with a proximal tubular origin. They also bear characteristics of accessory cells such as processing and presentation of antigen and TNF-alpha gene expression. We speculate that PT have the capacity to participate in the pathogenesis of immune renal injury.
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PMID:MHC class II, antigen presentation and tumor necrosis factor in renal tubular epithelial cells. 240 90

Recombinant human interleukin-1 beta, a mediator of osteoblastic cell function, was found to regulate the expression of the cell adhesion receptors, integrins, on human osteosarcoma cells. Interleukin-1 beta (IL-1 beta) at picomolar concentrations, specifically elevated approximately six- to tenfold the expression of the beta 1 subunit and its associated alpha subunits, but not the related vitronectin receptor, within 20 hours. Integrin beta 1 messenger RNA levels were elevated within 6 hours and peaked to tenfold higher levels after 20 hours exposure to IL-1 beta in two human osteosarcoma cell lines. The increase in the cell-surface beta 1 integrins resulted in a stronger binding of the IL-1 beta-treated cells to fibronectin. Cell growth was also inhibited by IL-1 beta, cell morphology was altered, and IL-1 beta-treated cells expressed an approximately two- to threefold higher alkaline phosphatase. This increase in alkaline phosphatase activity was found to be independent of the inhibition of cell proliferation. These data indicate that the beta 1 integrin family of cell surface receptors is a target for regulation by IL-1 beta, which also regulates cell proliferation and the expression of the osteoblastic phenotype in human osteosarcoma cells.
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PMID:Regulation of expression of the cell adhesion receptors, integrins, by recombinant human interleukin-1 beta in human osteosarcoma cells: inhibition of cell proliferation and stimulation of alkaline phosphatase activity. 252 62

A cell line, called MG-63.3A, was selected for its resistance to detachment from cell culture by a synthetic peptide containing the fibronectin cell-attachment sequence, Arg-Gly-Asp-Ser. The mechanism of this resistance is probably the 6-fold overproduction of the cell surface fibronectin receptor in MG-63.3A cells (Dedhar et al, J. Cell. Biol. 105, 1175-1182, (1987]. Compared to the parental, tumorigenic MG-63 cells, the non-tumorigenic MG-63.3A cells display strikingly different properties. These include an altered morphology, a slower proliferation rate, ability to form a calcified matrix in vitro, increased synthesis of type I collagen and expression of bone type alkaline phosphatase activity. Studies with purified growth factors indicate that the MG-63 and MG-63.3A cell lines respond to differentially to growth factors; the growth of MG-63 cells if stimulated by PDGF and GM-CSF and inhibited IL-1 beta, whereas the growth of MG-63.3A is unaffected by GM-CSF and IL-1 beta but is stimulated by PDGF and estradiol. We conclude from these data that the MG-63.3A cells may represent a more differentiated cell type with osteoblast-like properties. Studies are currently underway to further characterize, by electron microscopy, the calcified matrix formation by MG-63.3A cells.
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PMID:The osteoblast-like differentiated phenotype of a variant of MG-63 osteosarcoma cell line correlated with altered adhesive properties. 253 54

The effect of the bone resorptive cytokines IL-1 alpha, IL-1 beta, and TNF on bone formation was studied in an in vitro system. All three cytokines were profoundly inhibitory, with the rank order of potency IL-1 beta greater than IL-1 alpha greater than TNF. Inhibition was mediated by a depression of differentiated osteoblast functions, including alkaline phosphatase expression and matrix synthesis. Osteoblast proliferation was not affected. Bone formation inhibition was independent of PGE2 production, indicating a direct effect of cytokines on osteoblasts. High concentrations of IL-1 beta (10 U/ml) abrogated IGF-1-stimulated bone formation, providing evidence for the hypothesis that cytokines act as 'uncoupling factors'. Conversely, high concentrations of IGF-1 circumvented inhibition by IL-1 beta (0.1-1.0 U/ml). The interaction of cytokines and bone growth factors with osteoblasts are likely to be of critical importance in the regulation of bone mass at local inflammatory sites.
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PMID:Effect of immune cytokines on bone. 265 11

An immunoenzymatic detection method of in-situ hybridization reactions for interleukin 1 (IL-1) beta was established, using sulphonated probes. As model system we used unstimulated and lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMNC). After hybridization, sulphone groups were targeted with a monoclonal antibody, and bound antibody was visualized by the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. In unstimulated PBMNC both the control and the IL-1 beta specific c-DNA probes were negative, whilst a large proportion of LPS treated PBMNC was positive with the sulphonated IL-1 beta plasmid only. This method may be a powerful alternative to radio-isotopic labeling. Since the entire procedure can be performed within one day, it may be applied for routine diagnostic purposes.
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PMID:Immunoenzymatic assessment of IL-1 beta mRNA by in situ hybridization using sulphonated probes. 267 55

We have shown that natural homogenous IL-1 beta exhibits regulatory activities on human bone-derived osteoblast-like cells in vitro. IL-1 beta stimulated cellular proliferation and the synthesis of prostaglandin E2 and plasminogen activator activity by the cultured human osteoblast-like cells. In contrast to these stimulatory actions, IL-1 beta antagonised the stimulatory effects of 1.25(OH)2 D3 on the production of alkaline phosphatase and osteocalcin, two markers of the osteoblast phenotype. These studies indicate that this cytokine may therefore have potential physiological and pathological effects on bone metabolism.
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PMID:Natural human IL-1 beta exhibits regulatory actions on human bone-derived cells in vitro. 278 76


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