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

We investigated the effects that the combination of IL-1 alpha and transforming growth factor-beta (TGF-beta) had on PGE2 production in a murine clonal osteoblastic cell line MC3T3-E1 and primary rat calvarial osteoblast-like cells. In serum-supplemented medium, IL-1 alpha was a potent stimulator of PGE2 production in MC3T3-E1 cells (50-fold increase with 0.1 ng/ml). TGF-beta (10 ng/ml) had only a small effect alone and no additional effect on IL-1 alpha-induced responses. In serum-deprived MC3T3-E1 cells, PGE2 responses to IL-1 alpha were either absent or markedly reduced. TGF-beta alone had small effects. However, simultaneous addition of TGF-beta with IL-1 alpha to MC3T3-E1 cells partially restored the ability of IL-1 alpha to generate a PGE2 response (10-fold increase in PGE2 with 0.1 ng/ml of both IL-1 alpha and TGF-beta). As with MC3T3-E1 cells, serum-deprived primary fetal rat calvarial osteoblastic cells also did not respond to IL-1 alpha, unless TGF-beta was present in the medium (sixfold increase in PGE2 with 0.1 ng/ml IL-1 alpha and 10 ng/ml TGF-beta). The synergistic effect of TGF-beta and IL-1 alpha was specific for PGE2 responses, because these factors did not synergistically affect cell proliferation, collagen and noncollagen protein synthesis, or alkaline phosphatase activity. The observed synergy was not associated with changes in the steady state cyclooxygenase (PGH synthase) mRNA levels. However, it did correlate with increased release of [3H]arachidonic acid from prelabeled serum-depleted MC3T3-E1 cells. Hence, the synergistic interactions of IL-1 alpha and TGF-beta on PGE2 appear to occur through an increase in the release of arachidonic acid substrate from phospholipid pools. These effects may be important for both normal bone turnover and the responses of bone to inflammatory and immune stimuli.
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PMID:Effects of transforming growth factor-beta and IL-1 alpha on prostaglandin synthesis in serum-deprived osteoblastic cells. 170 13

Human endocrine thyroid epithelial cells have been described to produce cytokines in vitro. In order to determine whether they do so in vivo during thyroiditis, parallel studies on mRNA expression with a non-radioactive in situ hybridization technique and immunohistochemical detection for the protein were performed on frozen sections of thyroid samples from autoimmune thyroiditis (Graves' disease and Hashimoto's thyroiditis), non-toxic goitre and normal thyroid tissue. cDNA probes were sulphonated and their hybridization with mRNA was detected with a sulphonyl-specific monoclonal antibody. This signal was amplified and visualized with the alkaline phosphatase-anti-alkaline phosphatase (APAAP) system. The protein products were detected with immuno-purified rabbit F(ab')2 antibody fragments recognizing recombinant human cytokines, visualized by the immunoperoxidase technique. Each sample was studied at the two levels. Both interleukin-6 mRNA and protein were found in the endocrine cells. There was no obvious difference between autoimmune thyroiditis and non-toxic goitre. However, normal thyroid epithelial cells produced less interleukin-6. Interleukin-1 alpha mRNA and its protein were found in epithelial cells from Hashimoto's thyroiditis samples, but not in the others, except one Graves' disease sample, in which only mRNA was detected. Interleukin-1 beta was not detected in these cells, its mRNA was only found in one of the Graves' disease samples. These cytokines were also detected in some infiltrating cells.
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PMID:Detection of interleukin-6 and interleukin-1 production in human thyroid epithelial cells by non-radioactive in situ hybridization and immunohistochemical methods. 199 63

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

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

Both interleukin-1 alpha (IL-1 alpha) and IL-1 beta are initially translated as approximately Mr 30,000 polypeptides, lacking hydrophobic or signal sequence that could facilitate transmembrane translocation and release of mature IL-1 (Mr 17,500). The current study utilizes an antiserum specific for murine IL-1 alpha in order to investigate membrane associated IL-1 alpha polypeptides and possible postsynthetic modifications of the IL-1 alpha precursor, that might account for its intracellular transport. Cell surface iodination of endotoxin stimulated murine macrophages allowed the detection of IL-1 molecules in size similar to the IL-1 alpha precursor (Mr 33,000). Membrane bound IL-1 alpha was sensitive to degradation by serine esterase activity to yield IL-1 peptides of Mr 16,000 to 18,000. Endotoxin stimulated macrophages, but not unstimulated cells, incorporated 32PO4 into the IL-1 alpha precursor. The phosphate label of the IL-1 alpha precursor is resistant to hydroxylamine and alkaline phosphatase treatment. Released IL-1 is not phosphorylated. Approximately 10% of the phosphorylated IL-1 alpha precursor is membrane bound and associated with fractions enriched in lysosomal vesicles. These data are consistent with a model for mIL-1 expression, in which pro IL-1 alpha is post-synthetically modified to achieve intracellular transport and further suggest that mIL-1 may be a prerequisite for the release of IL-1.
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PMID:Structure and function of membrane IL-1. 326 77

A mutual antagonism exists between interleukin-1s (IL-1s) as pro-inflammatory and glucocorticoids as anti-inflammatory mediators. This report examines the effects of IL-1 on the induction by dexamethasone of alkaline phosphatase in LEII murine endothelial cells. Dexamethasone increases the specific activity of alkaline phosphatase in a time- and dose-dependent fashion (maximum 14-fold induction at 10(-6) M, IC50 = 10(-8) M), and this induction can be completely inhibited by simultaneous incubation with picomolar concentrations of recombinant human IL-1 alpha or IL-1 beta. This IL-1-mediated antagonism of dexamethasone activity is not due to a down-regulation of glucocorticoid receptors in the cell line used, because the number of receptors and their affinity for dexamethasone is unchanged in IL-1-treated cells. However, induction of alkaline phosphatase by dexamethasone in LEII cells is receptor-mediated, since it can also be inhibited by glucocorticoid-receptor antagonists.
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PMID:Recombinant human interleukin-1 inhibits the induction by dexamethasone of alkaline phosphatase activity in murine capillary endothelial cells. 350 Sep 55

Groups of BALB/c mice were treated with a sub-lethal dose (60 micrograms) of staphylococcal enterotoxin B (SEB) intraperitoneally and were sacrificed at 2, 5, 8, or 10 h post-injection. Organ, blood plasma and lymph node samples from these mice were analyzed. Plasma levels of urea, creatinine and alanine aminotransferase were significantly raised above normal by 5 h post-injection. However, alkaline phosphatase levels showed an erratic increase after toxin administration and, after administration of 10-40 microgramS SEB per mouse, were consistently at least 30% below normal levels at 24 h post-injection. Weight change was also monitored but found to be inconsistent. Lung, spleen and kidney samples appeared normal on histopathological examination, but liver samples showed minor polymorph infiltration and congestion. TNF-alpha, and IL-1 alpha levels in the plasma were raised by 8 h to picogram levels per ml of plasma, whereas IFN-gamma and IL-2 were raised by 2 h to nanogram levels per ml of plasma. Lymph node cells taken from mice treated with toxin were given a secondary stimulation with toxin in vitro. Although the response of the cells was lower than normal on assay at four days, a time response curve showed a peak in cell responsiveness to secondary stimulation with toxin at three days. These data indicate that biochemical markers and cytokine levels are affected by the administration of SEB to mice and may be used as indicators of toxicity.
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PMID:Staphylococcal enterotoxin B toxicity in BALB/c mice: effect on T-cells, plasma cytokine levels and biochemical markers. 764 Jun 77

The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified.
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PMID:Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells. 784 Oct 35

beta-Alanyl-L-histidinato zinc (AHZ), which is an activator of bone formation, has an inhibitory effect of bone resorption. Whether AHZ can inhibit the effect of parathyroid hormone (PTH) or interleukin-1 alpha (IL-1 alpha), which is a bone resorbing factor, on osteoblastic MC3T3-E1 cells was investigated. After subculture for 3 days, the cells were cultured for 48 h with peptides. Parathyroid hormone (10(-9)-10(-7) M) or IL-1 alpha (50 U/ml) caused a significant decrease in the cellular alkaline phosphatase activity and a remarkable increase of prostaglandin E2 (PGE2) production in the cells. Parathyroid hormone (10(-7) M) or IL-1 alpha (50 U/ml) did not have an appreciable effect on the protein content of the cells. beta-Alanyl-L-histidinato zinc (10(-5) M) significantly increased the cellular alkaline phosphatase activity and protein content, whereas it had no effect on PGE2 production. This increasing effect of AHZ was also seen in the presence of PTH (10(-7) M) or IL-1 alpha (50 U/ml), although the effect of PTH and IL-1 alpha to stimulate PGE2 production was not modulated by AHZ treatment. The present finding suggests that the inhibitory effect of AHZ on bone resorption is not through osteoblasts.
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PMID:Effect of parathyroid hormone and interleukin-1 alpha in osteoblastic MC3T3-E1 cells: interaction with beta-alanyl-L-histidinato zinc. 793 38


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