Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of protein kinase C by phorbol esters is known to accelerate the processing and secretion of the beta/A4 amyloid protein precursor. We have now examined various first messengers that increase protein kinase C activity of target cells for their ability to affect beta/A4 amyloid protein precursor metabolism. Acetylcholine and interleukin 1, which are altered in Alzheimer disease, were shown to increase processing of the beta/A4 amyloid protein precursor via the secretory cleavage pathway. Cholinergic agonists stimulated secretion in human glioma and neuroblastoma cells as well as in PC12 cells transfected with the M1 receptor, while interleukin 1 stimulated secretion in human endothelial and glioma cells.
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PMID:Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor. 135 34

Cytokines have various kinds of functions, including immunoregulation, host defense system, induction of inflammation and pathogenesis of many diseases. One of the characteristics of cytokines is the interaction among cytokines, and they further play an important role in the defense against tumor development, although its mechanism is highly complicated. In this paper, cytokines possessing antitumor activity, are described. These are 2 categories of antitumor cytokines, immunological and non-immunological ones. As immunological cytokines, interferons, interleukin 1, 2, 4, 5, 6, 8 and 12, tumor necrosis factor and lymphotoxin, have been investigated. On the other hand, tumor-degenerating factor, tumor regressing factor, glial maturation factor, glial growth inhibitory factor, neuroblastoma growth inhibitory factor, neonatal brain derived carcinostatic factor, chondromodulin and gliostatin have been characterized as non-immunological antitumor cytokines. These cytokines interact, and the complicated network of immunological and non-immunological antitumor cytokines is formed.
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PMID:[Antitumor cytokines]. 143 61

Expression of the lymphokine genes in human astroglial cell lineage was studied. Primers for 9 different human lymphokines, from IL-1 alpha to IL-8, were used to analyze RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell line and 4 fresh brain specimens by polymerase chain reaction (PCR). mRNA transcripts of neither IL-1 nor IL-3, the biological activities of which were observed in rat primary cultured astrocytes, could be detected within these cell lines. Two out of 5 unstimulated astrocytomas, U138 and U373, expressed IL-6 genes. IL-8 gene was detected within U87, U138, U251, U373 glioma cells. After stimulation with IL-1 beta, all astrocytoma and one neuroblastoma cell line expressed IL-6 and IL-8 genes. In addition to the cultured cells, we examined IL-6 and IL-8 gene expression within human malignant astrocytoma specimens. The result shows that three out of four glioma specimens expressed IL-6 and IL-8 genes. From these results, it is suspected that astroglial cell-derived IL-6 or IL-8 may participate in local immune reactions accompanying infection, degeneration and malignancies in the central nervous system.
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PMID:[An analysis of lymphokine gene expression within astrocytoma]. 163 May 67

In order to determine the pathogenesis of fever in solid tumors, we studied the association of fever at diagnosis in children with solid tumors (malignant lymphoma, rhabdomyosarcoma, and neuroblastoma), serum levels of interleukin 1 (IL-1), and tumor necrosis factor. Thirteen of 20 patients (65%) with solid tumors were complicated with fever at diagnosis. There was no difference in C-reactive protein or IL-1 levels between the patients with and without fever, while the erythrocyte sedimentation rate and TNF levels were higher in the former than in the latter by Wilcoxon's rank sum test (p less than 0.01). These findings suggest that most febrile episodes at diagnosis in children with solid tumors are associated with the release of tumor necrosis factor.
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PMID:Tumor necrosis factor and fever at diagnosis in children with solid tumors. 169 36

The Ly-6 locus contains multiple genes encoding cell surface proteins, two of which, when cross-linked by antibodies, effect antigen-independent activation of T lymphocytes. In this study, cDNA for Ly-6-encoded antigens have been used as probes to examine RNA from various tissues and transformed cell lines for constitutive levels of Ly-6 RNA expression. Analyses of RNA prepared from several different tissues revealed a high level of expression of Ly-6 RNA in kidney, spleen, heart and thymus, with a more moderate level of expression in liver, brain and lung tissue cells. A survey of various cell lines demonstrated the presence of Ly-6 RNA in many, but not all T lymphocytic cell lines, in L cells, the Meth A fibrosarcoma, in the TCMK kidney cell line, and in the Neuro-2a neuroblastoma. We also evaluated the expression of Ly-6 RNA in cells after treatments with interferons (IFN) and interleukin 1 (IL1). Treatment of lymphoid cells with IFN (alpha/beta and gamma), known to increase cell surface Ly-6 antigen expression in normal T cells, was correlated with increases in Ly-6 RNA levels. Increases in levels of RNA correlated with increases in levels of the Ly-6A/E or Ly-6C antigens. Several T lymphoid cell lines exhibiting Ly-6 RNA inducibility by IFN were similarly inducible with IL1. Kinetic experiments using one such line, (YAC-1), showed that the induction of Ly-6 RNA mediated by IFN-alpha/beta occurred rapidly (within 4 h), while the induction by IL1 required relatively more time (approximately 8 h). Although the actions of IFN-alpha/beta were not blocked by cycloheximide, the presence of this protein synthesis inhibitor significantly attenuated the effects of IL1 and IFN-gamma on Ly-6 RNA transcription. Induction by IFN-gamma as well as IL1 could be blocked completely by co-culture with anti-IFN-gamma, implicating IFN-gamma as a mediator of the induction by IL1.
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PMID:Kinetic analysis of Ly-6 gene induction in a T lymphoma by interferons and interleukin 1, and demonstration of Ly-6 inducibility in diverse cell types. 247 47

We have analyzed the modulation of amyloid beta-protein precursor (APP) gene expression in human umbilical vein endothelial cells (HUVEC). The level of the APP mRNA transcripts increased as HUVEC reached confluency. In confluent culture the half-life of the APP mRNA was 4 hr. Treatment of the cells with human-recombinant interleukin 1 (IL-1), phorbol 12-myristate 13-acetate, or heparin-binding growth factor 1 enhanced the expression of APP gene in these cells, but calcium ionophore A23187 and dexamethasone did not. The protein kinase C inhibitor 1-(isoquinolinsulfonyl)-2-methylpiperazine (H7) inhibited IL-1-mediated increase of the level of APP transcripts. To map IL-1-responsive elements of the APP promoter, truncated portions of the APP promoter were fused to the human growth hormone reporter gene. The recombinant plasmids were transfected into mouse neuroblastoma cells, and the cell medium was assayed for the human growth hormone. A 180-base-pair region of the APP promoter located between position -485 and -305 upstream from the transcription start site was necessary for IL-1-mediated induction of the reporter gene. This region contains the upstream transcription factor AP-1 binding site. These results suggest that IL-1 upregulates APP gene expression in HUVEC through a pathway mediated by protein kinase C, utilizing the upstream AP-1 binding site of the APP promoter.
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PMID:Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. 250 93

Although binding sites for IL-1 have been identified in the mouse brain, it is still unknown whether these binding sites correspond to the type I or type II IL-1 receptor. Quantitative autoradiography was used to confirm the presence of specific binding sites for radiolabelled recombinant human IL-1 alpha (125I-HuIL-1 alpha) in the brain of DBA/2 mice. IL-1 binding was highest in the dentate gyrus, consisting of a single class of high affinity binding sites with a Kd of 0.1 nM and a Bmax of 57 fmol/mg protein. A similar Kd of 0.2 nM was obtained using isolated membranes from the whole hippocampus, although the number of binding sites was lower (2 fmol/mg protein). Affinity cross-linking of 125I-Hu-IL-1 alpha to hippocampal membranes revealed the existence of two types of IL-1 receptor proteins, consistent with the sizes of the type I (85 kD) and type II (60 kD) IL-1 receptor. Oligonucleotide probes were then synthesized and used in RT-PCR followed by Southern blotting to show that the whole brain expresses transcripts for both the type I and type II IL-1 receptors. The murine neuroblastoma cell line, C1300, expresses type I rather than type II IL-1 receptor mRNA. The type I receptor protein can be identified by flow cytometry on the membrane of the C1300 neuronal cell line using indirect immunofluorescence with a rat anti-mouse type I IL-1 receptor MoAb. These data show that mouse brain expresses both type I and type II IL-1 receptor mRNA and proteins and offer further support to the idea that type I IL-1 receptors are synthesized and expressed by neurons.
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PMID:Expression of type I and type II interleukin-1 receptors in mouse brain. 787 56

In order to elucidate the role of inflammatory cytokines in the central nervous system, we examined the production of two leukocyte chemoattractants, IL-8 and monocyte chemotactic and activating factor (MCAF) in brain tumor cell lines. The glioma cell lines tested exhibited high levels of IL-8 and MCAF mRNA expression upon stimulation with IL-1 or TNF-alpha, while none of the neuroblastoma cell lines expressed these cytokine mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-1 alpha and TNF-alpha and appeared very rapidly, reaching maximal levels at 3-6 hr, with substantial production of these cytokines in the culture supernatants. When various immunosuppressive drugs were tested, glucocorticoids but not other immunosuppressive drugs markedly inhibited the IL-1 or TNF-alpha-induced IL-8 and MCAF mRNA accumulation, suggesting that glucocorticoid is a potent regulator of these inflammatory cytokine production in the neural tissues. In addition, reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of IL-8 and MCAF mRNA expression in resected brain tumor tissues including glioblastoma, astrocytoma grade 2, ependymoma and medulloblastoma, indicating that these inflammatory cytokines are expressed in vivo.
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PMID:Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues. 811 36

Human neuroblastoma cells SK-N-SH express significant numbers of IL-1R type I on their surface, as detected by saturation binding and RT-PCR, and are responsive to IL-1beta activation by producing inflammatory cytokines IL-6 and IL-8. IL-1beta can also have an indirect effect on nervous cell functions, since it is able to modulate the stimulus-induced increase of intracellular Ca++ levels, one of the first steps of the cell activation mechanism. In fact, on SK-N-SH neuroblastoma cells, IL-1beta can inhibit the Ca++ increase induced by stimulation of acetylcholine receptors with carbachol. In parallel to IL-1beta, the neurotrophic factor CNTF also shows an inhibitory effect on carbachol-stimulated Ca++ increase in CNTFRalpha-expressing SK-N-SH cells. However, when simultaneously present, the two cytokines cross-inhibit, thus allowing full cell activation in response to the cholinoceptor agonist. The inhibitory effect of CNTF on IL-1beta activities on nervous cells was confirmed in the IL-6 production assay. In fact, while CNTF could not induce IL-6 production, it could strongly inhibit cytokine production in response to IL-1beta in SK-N-SH cells. The down-modulation of IL-1 effects by CNTF could be one of the mechanisms controlling the extent of the inflammatory reaction at the nervous system level.
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PMID:Interaction between interleukin-1 and ciliary neurotrophic factor in the regulation of neuroblastoma cell functions. 945 16

Human SK-N-AS neuroblastoma and U-87MG glioblastoma cell lines were found to secrete relatively high levels of glial cell line-derived neurotrophic factor (GDNF). In response to growth factors, cytokines, and pharmacophores, the two cell lines differentially regulated GDNF release. A 24-hr exposure to tumor necrosis factor-alpha (TNFalpha; 10 ng/ml) or interleukin-1beta (IL-1,; 10 ng/ml) induced GDNF release in U-87MG cells, but repressed GDNF release from SK-N-AS cells. Fibroblast growth factors (FGF)-1, -2, and -9 (50 ng/ml), the prostaglandins PGA2, PGE2, and PGI2 (10 microM), phorbol 12,13-didecanoate (PDD; 10 nM), okadaic acid (10 nM), dexamethasone (1 microM), and vitamin D3 (1 microm) also differentially effected GDNF release from U-87MG and SK-N-AS cells. A result shared by both cell lines, was a two- to threefold increase in GDNF release by db-cAMP (1 mM), or forskolin (10 microM). In general, analysis of steady-state GDNF mRNA levels correlated with changes in extracellular GDNF levels in U-87MG cells but remained static in SK-N-AS cells. The data suggest that human GDNF synthesis/release can be regulated by numerous factors, signaling through multiple and diverse secondary messenger systems. Furthermore, we provide evidence of differential regulation of human GDNF synthesis/release in cells of glial (U-87MG) and neuronal (SK-N-AS) origin.
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PMID:Differential regulation of glial cell line-derived neurotrophic factor (GDNF) expression in human neuroblastoma and glioblastoma cell lines. 997 21


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