Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were conducted to explore the possible effect of low-dose irradiation on cytokine production in mice. SJL/J and C57BL/6J mice were exposed to 3 Gy and 4 Gy respectively. At various time intervals thereafter, lung-conditioned media, bone-marrow-conditioned media and sera were collected. Interleukin-6 and macrophage-colony-stimulating-factor activities were tested. Interleukin-6 in lung-conditioned media from both strains was found to be significantly induced by irradiation. Macrophage-colony-stimulating-factor activity was greatly enhanced in sera of irradiated SJL/J mice as well as in bone-marrow-conditioned media of both strains. The kinetics of the radiation-induced interleukin 6 and macrophage-colony-stimulating-factor activity differed in the 2 strains. SJL/J and C57BL/6J mice have been previously shown to be susceptible to low-dose-radiation-induced leukemia. The coleukemogenic effects of both cytokines in 3 different models of experimental leukemogenesis is demonstrated.
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PMID:Low doses of radiation induce systemic production of cytokines: possible contribution to leukemogenesis. 837 Jun 25

Oncostatin M (OM), a 28 kilodalton glycoprotein cytokine, is structurally and functionally related to interleukin 6 and leukemia-inhibitory factor. We reported previously that OM strongly up-regulated low density lipoprotein (LDL) receptors in human liver cells by a tyrosine kinase-mediated mechanism. Now, we demonstrate that the transcription factor Egr-1 is induced by OM. The induction of Egr-1 was time and concentration dependent; maximal inductions of 10-fold occurred by 30 min at concentrations of 10-25 ng/ml and higher. This concentration dependency was identical to those for OM-mediated tyrosine phosphorylation and LDL receptor up-regulation. The Egr-1, tyrosine kinase, and LDL receptor responses were inhibited at similar concentrations of genistein, suggesting that induction of Egr-1 and up-regulation of LDL receptors depended on activation of tyrosine kinase by OM. In contrast, depletion of protein kinase C by preincubation with 4 beta-phorbol 12-myristate 13 alpha-acetate did not affect OM-mediated induction of Egr-1 or up-regulation of LDL receptors, indicating that protein kinase C is not required for the OM action. Other similar cytokines were investigated, and, of these, only interleukin 1 could increase both Egr-1 and LDL receptor activity. The correlation among tyrosine kinase phosphorylation, Egr-1 induction, and LDL receptor regulation suggests that Egr-1 may be a nuclear signal transducer utilized by OM to induce transcription of the LDL receptor gene. In support of this possibility is the discovery of an Egr-1 consensus sequence (GAGGGGGCG) at approximately 330 base pairs upstream from the transcription initiation site of the LDL receptor promoter region.
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PMID:Induction of Egr-1 by oncostatin M precedes up-regulation of low density lipoprotein receptors in HepG2 cells. 839 2

Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) produce high levels of interleukin 6 (IL-6), which is suggested to play an important role in thrombocytosis, elevation of C-reactive protein, and hypercalcemia in ATL. In this study, we investigated the effects of T-cell growth factors such as interleukin 2 (IL-2) and interleukin 4 (IL-4) on IL-6 production by ATL cells in vitro. Although IL-2 and/or IL-4 enhanced the cell proliferation of freshly isolated ATL cells from seven of nine patients, IL-2 did not affect the IL-6 release in most cases. In contrast, another T-cell tropic factor, IL-4 markedly inhibited the release of IL-6 in the conditioned medium in all cases. This IL-4-mediated inhibition of IL-6 release was completely abrogated by the addition of anti-IL-4 monoclonal antibody. Time course experiments demonstrated that IL-4 reduced the secretion of IL-6 for a prolonged period of time (more than 72 h). By Northern analysis, IL-4 reduced the transcription level of IL-6 mRNA. Furthermore, by flow cytofluorometry with the use of anti-human IL-4 receptor monoclonal antibody, ATL cells showed the significant level of IL-4 receptor on their cell surfaces without any stimulation. These data suggest that IL-4 may play an important regulatory role in the production of IL-6 in ATL.
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PMID:Inhibitory effect of interleukin 4 on production of interleukin 6 by adult T-cell leukemia cells. 840 41

In order to clarify the role of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF alpha) in the pathogenesis of acute leukemia, IL-6 and TNF alpha level was determined in patients with various types of acute leukemia. In comparison with normal subjects, IL-6 activity was significantly elevated in patients with ALL and ANLL (P < 0.01) and TNF alpha level increased in patients with ANLL (P < 0.05). The effect of IL-6 and TNF alpha on leukemia cell in vitro was also observed. The results indicated that IL-6 can promote the proliferation of leukemia cells, while TNF alpha can inhibit proliferation of leukemia cell in vitro. It is suggested that abnormal level of TNF alpha and IL-6 in patients with acute leukemia is probably related to the pathogenesis of acute leukemia.
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PMID:[Tumor necrosis factor and interleukin 6 in acute leukemia]. 840 30

Serum concentrations of E-selectin (CD62E), P-selectin (CD62P), ICAM-1 (CD54) and interleukin 6 were investigated in acute leukaemia patients with chemotherapy-induced leucopenia and complicating bacterial infections. Serum concentrations of both E-selectin and P-selectin were decreased in the leucopenic patients without infections when compared with levels before chemotherapy; and serum concentrations of both E-selectin and P-selectin showed a further decrease during complicating bacterial infections. In contrast to the leukaemia patients, previously healthy individuals with meningococcal disease showed markedly elevated serum concentrations of E-selectin and normal levels of P-selectin during infection. Serum concentrations of ICAM-1 and interleukin 6 increased during bacterial infections in the acute leukaemia patients with chemotherapy-induced leucopenia. The alterations in serum concentrations of soluble adhesion molecules and interleukin 6 reversed when clinical signs of bacterial infections resolved during antibiotic therapy. Our results demonstrate that acute leukaemia patients with chemotherapy-induced cytopenia show altered levels of both soluble adhesion molecules and interleukin 6 during complicating bacterial infections.
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PMID:Serum concentrations of E-selectin, P-selectin, ICAM-1 and interleukin 6 in acute leukaemia patients with chemotherapy-induced leucopenia and bacterial infections. 854 81

The ability of total body irradiation (TBI) to eradicate clonogenic leukemia cells from B-lineage acute lymphoblastic leukemia patients prior to bone marrow transplantation (BMT) is greatly hampered by their inherent or acquired radiation resistance. The radiorefractory nature of these cells is believed to contribute to the high relapse rate subsequent to TBI and BMT in patients with B-lineage acute lymphoblastic leukemia (ALL). A method by which clonogenic leukemia cells could be radiosensitized in vivo could be clinically beneficial. In the present study, we used a highly radiation resistant subclone of the murine B-lineage leukemia cell line BCL-1 in a syngeneic BMT model to investigate if any of the B-cell stimulatory cytokines interleukin 2, interleukin 4, interleukin 5, or interleukin 6 could have radiosensitizing effects. All untreated BALB/c mice (N = 33) inoculated with 1 x 10(6) BCL-1 cells died of disseminated leukemia within 24 days with a median survival of 13.3 days. TBI (700 cGy = LD100/30 for BALB/c mice) followed by syngeneic BMT (N = 70) extended the median survival to 23.6 days (P < 0.001 by log-rank test). A single intraperitoneal bolus injection of 100 ng, 500 ng, or 2500 ng recombinant murine interleukin 6(rmIL-6) 2-4 hours before TBI extended the median survival to 32.5 days, 31.0 days, and 30.5 days, respectively (P < 0.01 by log-rank test for all dose groups). The improved survival was not due to any direct anti-leukemic activity of rmIL-6 and all control BALB/c mice (N = 15) that received the same doses of rmIL-6 but did not undergo TBI and BMT died of BCL-1 leukemia within 28 days with a median survival of 13.6 days. In contrast to rmIL-6, recombinant murine interleukin 5 (rmIL-5) had minimal radiosensitizing effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo radiosensitizing effects of recombinant interleukin 6 on radiation resistant BCL-1 B-lineage leukemia cells in a murine syngeneic bone marrow transplant model system. 857 56

Leukaemia Inhibitory Factor (LIF), an interleukin 6 (IL-6)-type cytokine, is an essential growth factor for murine embryonal stem cells. The LIF-receptor was known in these cells, but the cell-internal part of the signal cascade and the transcription factors through which LIF controls its growth-promoting target genes in embryonal stem cells, had not been identified. This study shows that the type II IL-6-response element of the rat alpha 2 macroglobulin (alpha 2M) gene, which mediates IL-6- and LIF-responses in hepatic cells, also functioned as a LIF-response element (LIF-RE) in ES1 embryonal stem cells and P19 embryonal carcinoma cells. It conferred transcriptional activation by LIF of transfected reporter constructs in these cells. A characteristic DNA-binding activity interacting with this LIF-RE was induced by treatment of these cells with LIF. The complex between this activity and the LIF-RE had identical electrophoretic mobility, sequence-specificity and kinetics of induction as the complex with the corresponding LIF-response factor (LIF-RF) from hepatic cells. The transcription factor STAT3 was part of this complex, as shown by its reactivity with anti-STAT3 antibodies. Withdrawal of LIF from ES1 cells caused the induction of differentiation and the disappearance of this DNA-binding activity. Simultaneously, the surface density of high-affinity LIF receptors was reduced approximately 10-fold.
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PMID:The LIF response element of the alpha 2 macroglobulin gene confers LIF-induced transcriptional activation in embryonal stem cells. 858 Mar 64

Blast cells derived from peripheral blood of patients with acute myelogenous leukaemia (AML) were cultured in vitro and interleukin 1 receptor antagonist (IL1RA) concentrations determined in culture supernatants. AML blasts derived from patients classified as AML-M4 and AML-M5 subtype showed an increased release of IL1RA. IL1 alpha and IL1 beta caused a similar increase in AML blast release of IL1RA, and addition of anti-IL1 antibodies decreased IL1RA release. IL1RA release from AML blasts was also increased by stem cell factor, tumour necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, whereas interleukin 3, interleukin 6, leukaemia inhibitory factor and granulocyte colony-stimulating factor did not significantly alter IL1RA release. When investigating IL1RA serum levels, serum concentrations were decreased in acute leukaemia patients with chemotherapy-induced cytopenia compared with healthy controls. Serum levels of both IL1RA as well as IL1 beta and soluble TNF alpha receptors increased when the leucopenic patients developed complicating bacterial infections.
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PMID:Interleukin 1 receptor antagonist (IL1RA) in acute leukaemia: IL1RA is both secreted spontaneously by myelogenous leukaemia blasts and is a part of the acute phase reaction in patients with chemotherapy-induced leucopenia. 869 37

Toxohormones are tumor-derived factors that induce cancer cachexia syndrome in tumor-bearing animals. Nude mice bearing tumors induced by eight human cancer cell lines with this activity were studied for cytokine production and expression of a newly identified gene, ob, which has the ability to control body weight. A melanoma cell line, SEKI, and a neuroepithelioma cell line, NAGAI, produced a large amount of the cytokine, leukemia-inhibitory factor (LIF). A uterine carcinoma cell line, Yumoto, produced a large amount of interleukin 6 (IL-6), and an oral cavity carcinoma cell line, OCC-1C, concomitantly produced LIF, IL-6, and IL-11. Reverse transcription polymerase chain reaction studies revealed that ob gene mRNA was not expressed in any of these cell lines, suggesting that the gene does not have a role as a tumor product responsible for cancer cachexia in this model. These findings suggest that in four of eight animal models in which cancer cachexia syndrome developed, LIF, IL-6, or possibly IL-11 produced by cancer cells may be toxohormones, but in the remaining four cancer cell lines the mechanism responsible for cachexia syndrome remains unknown.
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PMID:Toxohormones responsible for cancer cachexia syndrome in nude mice bearing human cancer cell lines. 876 17

Oncostatin M (OSM) is structurally and functionally similar to leukaemia inhibitory factor (LIF), interleukin 6 (IL-6), interleukin 11 (IL-11) and ciliary neurotrophic factor (CNTF). We have previously shown that LIF stimulates proteoglycan release and suppresses proteoglycan synthesis in pig and goat cartilage explants. The aim of this study was to determine whether OSM and related cytokines influence proteoglycan metabolism in pig cartilage explants. Slices of pig articular cartilage were incubated for 6 days in serum free DMEM with or without cytokines. The total proteoglycan content in papain digested cartilage explants and medium was determined by the 1,9 dimethylmethylene blue method. Cytokine activity was assessed by determining the percentage release of total proteoglycan. To evaluate proteoglycan synthesis, cartilage was cultured for 48 h under the same conditions and in the final 6 h the tissue was cultured in sulphate free DMEM containing 35SO4. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose dependent stimulation of proteoglycan release and suppression of proteoglycan synthesis were observed with rhOSM. IL-6, IL-11 and CNTF also inhibited proteoglycan synthesis in a dose dependent manner but the degree of inhibition was less than that for OSM and these cytokines had no significant effect on proteoglycan release. New biological effects have been identified for OSM and the related cytokines CNTF and IL-11. All three of these cytokines, like LIF and IL-6, suppress proteoglycan synthesis in pig cartilage explants. This common effect suggests that the gp130 subunit of the receptors for these cytokines may represent a common signalling pathway whereby proteoglycan synthesis is regulated. Whilst OSM and LIF stimulate proteoglycan catabolism; IL-6 IL-11 and OSM do not. Thus these effects are not always coupled and activation of gp130 alone may not be a sufficient signal for proteoglycan catabolism.
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PMID:Oncostatin M (OSM) stimulates resorption and inhibits synthesis of proteoglycan in porcine articular cartilage explants. 881 47


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