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)

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

Neuroblastoma cells in response to retinoic acid (RA) exhibit differentiation. RA, which can promote tumor cell differentiation, has also been shown to regulate tumor-infiltrating leukocytes. In an attempt to explore the relationship between RA-induced neuroblastoma cell differentiation and leukocyte chemotaxis, we investigated expression of IL-1 beta, IL-8, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor-alpha in the undifferentiated and RA-induced differentiated neuroblastoma cells. Using SK-N-SH neuroblastoma cells, we found that RA induced differentiation of SK-N-SH cells as demonstrated by down-regulation of N-myc gene expression, cell-cycle arrest in G1 phase, and phenotypic change. Neither RA-treated nor untreated neuroblastoma cells expressed IL-1 beta, granulocyte-macrophage colony stimulating factor, or tumor necrosis factor-alpha mRNA. RA-treated but not untreated SK-N-SH cells expressed IL-8 mRNA in a time- and dose-dependent fashion. As determined by ELISA, IL-8 levels were detectable in the culture supernatants from RA-treated, but not untreated, neuroblastoma cells (2.65 +/- 0.43 versus 0.05 +/- 0.04 ng/mL). Using neutrophil and lymphocyte chemotactic assays, we found that RA-treated but not untreated culture supernatants of neuroblastoma cells promoted neutrophil and lymphocyte chemotaxis. The RA enhancement of neuroblastoma cell-mediated leukocyte chemotaxis was significantly blocked by anti-IL-8 neutralizing antibodies. These results suggest that RA-induced neuroblastoma cell differentiation is associated with production of functional IL-8, which may be involved in the leukocyte infiltration and activation resulting in tumor regression.
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PMID:Induction of interleukin-8 expression in neuroblastoma cells by retinoic acid: implication of leukocyte chemotaxis and activation. 810 82

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

To determine whether neural crest-derived neuroblastoma cells may release cytokines which regulate the function of leukocytes, we found that neuroblastoma (HTB-11) cells did not constitutionally express IL-1 beta, TNF alpha, or IL-8 mRNA. However, TNF alpha, which induced HTB-11 cells to differentiate to perineurium-like cells, induced expression of IL-8 mRNA in a dose- and time-dependent fashion. In contrast, pentoxifylline (1 mM), which promoted HTB-11 cells to differentiate to polygonal neuron-like cells, did not induce IL-8 mRNA expression. As determined by enzyme-linked immunoassay, high levels of IL-8 were detectable in the culture supernatants from TNF alpha-treated neuroblastoma cells, but not pentoxifylline-treated neuroblastoma cells (19.60 +/- 2.34 vs 0.10 +/- 0.06 ng/ml). Culture supernatants obtained from TNF alpha-treated neuroblastoma cells induced chemotaxis of neutrophils and lymphocytes that was significantly blocked by anti-IL-8 neutralizing antibodies. Detection of a leukocyte chemotactic factor was not observed in the culture supernatants from pentoxifylline-treated cells. These results suggest that neural crest-derived perineurium-like cells, but not neuron-like cells, may release a leukocyte chemotactic factor or factors such as IL-8 which could be involved in leukocyte recruitment seen in inflammatory diseases affecting peripheral nerves.
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PMID:Neuroblastoma cell-mediated leukocyte chemotaxis: lineage-specific differentiation of interleukin-8 expression. 812 47

The cell line AG-F was isolated from the marrow of a neuroblastoma patient undergoing myeloablative treatment and autologous bone marrow rescue. A year later, the patient developed a Hodgkin's type lymphoma. AG-F cell line demonstrated an unusual phenotype, lacking surface CD2 and CD3, but expressing high levels of CD4, CD5, CD7, CD29, and CD45RO. Markers associated with Hodgkin's lymphoma cells, CD15 and CD30, were also positive. AG-F cells grow in suspension in clusters of 50-200 cells, with a doubling time of 9 h. They can also grow in serum-free medium and form tumors in nude mice. AG-F cells have amplified N-myc and c-myc and high levels of the corresponding mRNA transcripts. Cytogenetic analysis revealed a DNA index by flow cytometry of near tetraploid cells and a karyotype of 85-87 chromosomes, with consistent abnormalities in chromosomes 1, 5, and 9. Gene rearrangement studies revealed rearrangement of the beta gene of the T-cell receptor. AG-F cells secrete high levels of IL-6, IL-8, IL-10, and GM-CSF. Cell adherence and formation of long processes could be induced by fibronectin and were enhanced by exposure to PMA. Cells exposed to phorbol myristate acetate (PMA) had increased expression of CD11a, CD11b, CD18, CD45RO, and HLA-DR, whereas expression of CD15 and CD30 was markedly decreased. Similarly, the level of c-myc and N-myc oncoproteins and the levels of the cytoskeletal proteins, actin, tubulin, and vimentin markedly decreased early after PMA-induced differentiation.
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PMID:Isolation and characterization of an early T-helper/inducer cell line with a unique pattern of surface phenotype, constitutive cytokine secretion and myc oncogene expression. 825 4

Neuroblastoma (NB) is a major-histocompatibility-complex(MHC)-negative neuroectodermal tumour that is often infiltrated with lymphocytes. A detailed characterization of NB-associated tumour-infiltrating lymphocytes (TIL) has never been carried out. Here we have investigated the immunophenotype and the cytotoxic activities of TIL from nine and seven NB patients respectively. Furthermore, the T cell receptor (TcR) variability and the patterns of cytokine gene expression of fresh versus recombinant (r) interleukin (IL)-2-cultured TIL were studied in four NB cases. The results obtained showed the following: (1) freshly isolated TIL were comprised of a mixture of CD4+ and CD8+ T cells partially expressing HLA-DR and/or CD25. The CD4/CD8 ratio ranged from 0.5 to 5 in the different cases. Upon culture of TIL with rIL-2, an increased proportion of CD56+ and CD8+ lymphocytes was consistently observed; (2) IL-2-expanded TIL lysed natural-killer(NK)sensitive and lymphokine-activated-killer(LAK)-sensitive target cell lines; (3) reverse-transcriptase/polymerase-chain-reaction (RT-PCR) experiments showed that most TcR V beta genes were expressed both in fresh and in cultured TIL, suggesting that such cell populations were polyclonal; (4) interferon gamma, IL-4, IL-5, tumour necrosis factor (TNF) alpha, IL-8, IL-10 mRNA and, to a lesser extent, IL-2 mRNA were expressed by cultured TIL, as assessed by RT-PCR; the corresponding tumour samples consistently contained TNF alpha, IL-8 and IL-10 mRNA, whereas IL-2 and IFN gamma mRNA were faintly expressed in some NB tumours and IL-4 and IL-5 mRNA were never detected. A total of 90 clones were subsequently raised from IL-2-expanded TIL from six NB patients; 87/90 clones were of T cell lineage with a CD4+ or CD8+ immunophenotype, whereas the 3 remaining clones were of NK cell origin. Upon triggering of the CD3-TcR complex, 64% CD4+ and 77% CD8+ T cell clones killed the murine P815 mastocytoma cell line. Virtually no T cell clone lysed a LAK-sensitive NB cell line whereas 15% CD4+ and 17% CD8+ clones mediated NK-like activity against the K562 cell line. Finally, the patterns of cytokine production by CD4+ clones were roughly consistent with those of a T helper (TH) 1 profile and similar to those observed in CD8+ clones.
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PMID:Functional and molecular characterization of tumour-infiltrating lymphocytes and clones thereof from a major-histocompatibility-complex-negative human tumour: neuroblastoma. 864 Aug 45

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

We investigated the effect of TNF alpha, IL-1alpha and IFN gamma on two neuroblastoma (NB) cell lines (SK-N-SH and SK-N-MC). These lines responded differentially to IL-1alpha, TNF alpha and IFN gamma for MCP-1 and IL-8 production and expression of the ICAM-1 and VCAM-1 adhesion molecules. None of the cytokines induced MCP-1 or IL-8 on SK-N-MC cells. Both chemokines were produced in response to IL-1alpha by SK-N-SH cells, while TNF alpha induced mainly MCP-1 production. Addition of IFN gamma decreased IL-8, but not MCP-1 production. These responses correlated with monocyte and neutrophil chemotactic activity in NB culture supernatants. This activity was neutralized by antibodies to IL-8 and MCP-1. The expression of ICAM-1 on SK-N-MC was up-regulated by TNF alpha or IFN gamma, while IL-1alpha also upregulated ICAM-1 on SK-N-SH cells. VCAM-1 expression on SK-N-SH was induced by IL-1alpha and TNF alpha and IFN gamma synergized with TNF alpha in this respect on both NB cell lines. These results suggest that mechanisms for chemokine production and VCAM-1 and ICAM-1 upregulation by inflammatory cytokines differ and IFN gamma, in conjunction with TNF alpha, stimulate neural cell responses (high MCP-1 and VCAM-1 and decreased IL-8) favouring mononuclear cell recruitment.
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PMID:Chemokine production and adhesion molecule expression by neural cells exposed to IL-1, TNF alpha and interferon gamma. 982 72

Glucocorticoids are potent antiinflammatory drugs. They inhibit the expression of proinflammatory cytokines and adhesion molecules. It has recently been proposed that the underlying basis to such inhibition is the induction of the protein I kappa B, which inhibits the transcription factor NF-kappa B. The latter is a key activator of the genes encoding cytokines and adhesion molecules. The present study shows that the synthetic glucocorticoid, dexamethasone, inhibits the induction of the proinflammatory cytokine IL-8 and the adhesion molecules VCAM-1 and ICAM-1 in human 1321N1 astrocytoma and SK.N.SH neuroblastoma cells. However, dexamethasone failed to induce I kappa B or inhibit activation of NF-kappa B by IL-1 in the two cell types. EMSA confirmed the identity of the activated NF-kappa B by demonstrating that an oligonucleotide, containing the wild-type NF-kappa B-binding motif, inhibited formation of the NF-kappa B-DNA complexes whereas a mutated form of the NF-kappa B-binding motif was ineffective. In addition, supershift analysis showed that the protein subunits p50 and p65 were prevalent components in the activated NF-kappa B complexes. The lack of effect of dexamethasone on the capacity of IL-1 to activate NF-kappa B correlated with its inability to induce I kappa B and the ability of IL-1 to cause degradation of I kappa B, even in the presence of dexamethasone. The results presented in this paper strongly suggest that glucocorticoids may exert antiinflammatory effects in cells of neural origin by a mechanism(s) independent of NF-kappa B.
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PMID:Antiinflammatory effects of glucocorticoids in brain cells, independent of NF-kappa B. 1043 51

Inflammatory cytokines and human immunodeficiency virus type 1 (HIV-1) gp120 are considered to play an important role in the pathogenesis of HIV-1-associated CNS disorders. These substances are produced predominantly by HIV-1-infected or activated macrophages and microglia in the brain and induce neural cell death. Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have anti-inflammatory, anti-allergic, and immunomodulatory activities in vivo. We previously reported that this compound could inhibit tumor necrosis factor (TNF)-alpha- or phorbol 12-myristate 13-acetate-induced HIV-1 replication in latently infected U1 cells through the inhibition of nuclear factor-kappaB, a potent inducer of HIV-1 gene expression. In the present study, we demonstrated that cepharanthine suppresses the production of inflammatory cytokines and a chemokine, i.e. TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-8, in human monocytic cell cultures, including primary monocyte/macrophage cultures. This effect of cepharanthine was concentration-dependent, and significant suppression was observed at 0.1 microg/mL. Furthermore, the compound also inhibited TNF-alpha- and gp120-induced death of differentiated human neuroblastoma cells at a concentration of 0.04 to 0.2 microg/mL. It penetrates the blood-brain barrier, and a medicine containing cepharanthine as a major component has been used in Japan for the treatment of patients with chronic inflammatory diseases. Thus, cepharanthine should be investigated further for its therapeutic and prophylactic potential in HIV-1-associated CNS disorders.
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PMID:Suppression of cytokine production and neural cell death by the anti-inflammatory alkaloid cepharanthine: a potential agent against HIV-1 encephalopathy. 1155 20


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