Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study the distribution and quantitation of the flt3/flk-2 receptor was examined on bone marrow cells and defined haemopoietic subpopulations. Undifferentiated cells expressed the greatest numbers of flt3/flk-2 receptors: 19% of primitive lin-kit+sca-1+ bone marrow cells and 16% of fetal liver lin-aa4.1+ cells exhibited over 15 000 receptors per cell as determined by binding of the radiolabeled cognate ligand (flt3/flk-2 ligand, FL). Moderate binding was demonstrated on early B lymphocyte subsets (4400 receptors per cell) and very low levels were detected on monocytes. Binding was not detected on promyelocytes, myelocytes, promonocytes, metamyelocytes, polymorphonuclear cells, eosinophils or nucleated erythroid cells. FL enhanced the survival of primitive lin kit+sca-1+ cells with an efficacy s with an efficacy equivalent to stem cell factor (SCF). FL stimulated predominantly blast and granulocyte-macrophage colony formation in cultures of bone marrow cells by both direct and indirect mechanisms. Marked synergistic effects of FL with combinations of colony stimulating factors (CSFs) or interleukin-6 occurred in the proliferation of primitive lin-kit+sca-1+ cells, but not lin-kit+sca-1- progenitor cells. Surprisingly, recloning experiments revealed that FL plus IL-3 increased the generation of progenitor cells by lin-kit a-1- cells compared with SCF plus IL-3. Thus FL functions as a factor with both direct and indirect stimulatory activities directed to the expansion, maintenance of clonogenic potential, and possibly limited self-renewal, of early haemopoietic cells.
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PMID:The flt3/flk-2 ligand: receptor distribution and action on murine haemopoietic cell survival and proliferation. 860 17

Stromal cell lines were established by irradiating adherent layers of bone marrow and spleen cells in Dexter-type long-term culture with X-rays. Some of these cell lines support myelopoiesis and/or B lymphopoiesis in vitro. Furthermore, the characteristics of these stromal cell lines were studied. Cytokine activity was detected in the conditioned media from all hematopoietic-supportive and non-supportive stromal cells. Quantitative reverse transcriptase-polymerase chain reaction analysis revealed that the mRNAs of macrophage colony-stimulating factor and stem cell factor, but not that of Interleukin-3, were detectable in all the hematopoietic-supportive and non-supportive stromal cell lines. The transcripts of granulocyte colony-stimulating factor, interleukin-6, interleukin-7, and leukemia inhibitory factor were expressed in a wide variety of cell lines. Most stromal cell lines synthesized mRNA of c-mpl, the ligand of which stimulates megakaryopoiesis and thrombopoiesis. These observations indicate that the pattern of mRNA expression of cytokines is not correlated with the hematopoietic-supportive ability of stromal cell lines. There was a significant difference in the efficiency of adhesion of lineage marker-negative bone marrow cells to fibroblasts and stromal cell lines. This appears to be correlated with the hematopoietic-supportive ability of the stromal cell lines.
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PMID:Characterization of murine stromal cell clones established from bone marrow and spleen. 865 75

Irradiated female mice were reconstituted with male hematopoietic stem cells (HSCs) retrovirally marked with human adenine deaminase (hADA) complimentary DNA. HSCs were incubated with interleukin-6 and stem cell factor before coculture with GP+E86-producing cells. Bone marrow HSCs were infused intravenously to irradiated mice and spleen colony-forming units (CFU-S) were evaluated for hADA marked clones by Southern blot analysis. 45 of 54 CFU-S were marked by the hADA gene sequence with multiple copies integrated per genome. Oligoclonal hematopoiesis evolved over time with 1-2 clones demonstrated 5-11 months after reconstitution. Comparable results were obtained with embryonic fetal liver HSCs. Incubation of bone marrow HSCs with adherent stromal cells rather than growth factors produced less efficient gene transfer, and polyclonal hematopoiesis was not observed. Donor origin was established by the Y chromosome probe. These results support the clonal succession model of hematopoiesis.
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PMID:Transfer of human adenine deaminase gene into murine hematopoietic stem cells: sequential study of spleen colony-forming units from bone marrow of living mice and the requirement of the microenvironment. 870 1

Patients with Gaucher disease suffer from a lack of functional glucocerebrosidase enzyme (Gc). Disease symptoms are a result of macrophage engorgement secondary to this enzyme deficiency. This study is designed to determine if cDNA encoding normal Gc can be introduced into macrophage precursors using a retroviral vector. CD34+ cells obtained from G-CSF mobilized peripheral blood stem cells or from bone marrow will be transduced ex vivo using one of the following three methods of transduction: 1) GlGc retroviral supernatant in the presence of autologous stroma over a period of 72 hours, 2) GlGc retroviral supernatant in the presence of interleukin-3, interleukin-6, stem cell factor and autologous stroma over a 72 hour period, 3) G1Gc retroviral supernatant in the presence of interleukin-3, interleukin-6, and stem cell factor over a 72 hour period. These transduced cells will be reinfused into the patient and the patient monitored for toxicities as well as evidence of successful gene transfer and expression. A total of twenty-four patients will be enrolled on the protocol. Patients will be assigned in equal numbers to each of six groups. The two sites participating are the National Institutes of Health and Childrens Hospital of Los Angeles.
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PMID:Retroviral mediated transfer of the cDNA for human glucocerebrosidase into hematopoietic stem cells of patients with Gaucher disease. A phase I study. 878 74

The effects of interleukins 3 and 6, stem cell factor, and granulocyte-macrophage colony-stimulating factor on human fetal hematopoietic, bone marrow, and cord blood cells were studied on the basis of the colony-forming capacity. Fetal hematopoietic cells from 28 elective abortions, three bone marrow samples, and three cord blond samples were incubated with cytokines and investigated for the presence of BFU-E (burst-forming units--erythroid), CFU-GM (colony-forming units--granulocytes, macrophages), and CFU-GEMM (colony-forming units--granulocytes, erythrocytes, macrophages, megakaryocytes). Single and combined cytokines and preincubation versus adding cytokines in culture were investigated. Interleukin-6 alone had the most pronounced effect on BFU-E formation. All four cytokines in combination yielded the highest scores for CFU-GM (p < 0.05) and CFU-GEMM (p < 0.05), whereas BFU-E was not enhanced. The mode of cytokine exposure was not a determinant of colony formation.
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PMID:Cytokine stimulation of human fetal hematopoietic cells. 889 26

Acute promyelocytic leukemia (APL) is characterized cytogenetically by the presence of a reciprocal translocation between chromosomes 15 and 17 [t(15;17)(q22-q24;q11-q21)] in the bone marrow cells in the majority of patients. Cytogenetic evaluation of bone marrow cultures from patients with APL is often technically difficult, due to frequent difficult marrow aspiration and the suboptimal quality of cytogenetic preparations. This has important implications for the cytogenetic detection of residual disease. This study examined the proliferative ability of the recombinant human growth factors-stem cell factor (SCF), interleukin-6 (IL-6), interleukin-3 (IL-3), and granulocyte macrophage-colony stimulating factor (GM-CSF)-to determine if they would provide a consistent improvement over the standard cytogenetic culturing techniques in terms of mitotic index (MI). In all cases, the MI of the growth factor stimulated cultures showed a considerably higher (3.5-198 fold) and statistically significant (p < 0.01) increase compared to the unstimulated cultures. We conclude that the use of recombinant human growth factors is potentially an effective way of increasing the MI in bone marrow cultures from APL patients for the purposes of diagnosis and residual disease detection.
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PMID:Combination of SCF, IL-6, IL-3, and GM-CSF increases the mitotic index in short term bone marrow cultures from acute promyelocytic leukemia (APL) patients. 890 73

The canine marrow stroma-derived CD34- DR- cell line D064 is able to differentiate into cells with characteristics of hematopoietic progenitors. While differentiating, these cells start to express CD34 and DR. Differentiation is induced by stem cell factor (SCF), while interleukin-6 (IL-6) inhibits differentiation, but promotes proliferation. The influence of SCF and IL-6 on differentiation and proliferation is reflected in the expression of p27kip-1. SCF induces a transient expression of p27kip-1, while no p27kip-1 is detectable in the presence of IL-6 or an anti-SCF monoclonal antibody. The accumulation of intracellular p27kip-1 precedes the differentiation of D064 cells. As these cells start to proliferate and more committed progenitors emerge, p27kip-1 is no longer expressed.
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PMID:Stem cell factor-induced expression of p27kip-1 during hematopoietic differentiation. 894 Oct 47

Myofibroblasts have been previously described beneath the bronchial epithelium and were found to increase in number proportional to the accumulation of extracellular matrix in the bronchial lamina reticularis in asthma. The aim of this study was to assess further the contribution of these structural cells to allergic inflammation in the bronchial mucosa through their cytokine expression. Cell cultures were established from the lamina reticularis of human bronchial biopsies from asthmatic and non-asthmatic subjects. Cytokine secretion was measured by ELISA in supernatants of cultures with or without tumour necrosis factor-alpha (TNF-alpha). The mRNA levels for granulocyte-macrophage colony-stimulating factor (GM-CSF) in the cultures were examined by ribonuclease protection assays (RPAs). Bronchial myofibroblasts grown from bronchial biopsies were capable of producing GM-CSF, interleukin-6 (IL-6), interleukin-8 (IL-8), and stem cell factor (SCF) constitutively. The GM-CSF production by myofibroblasts was significantly increased in response to TNF-alpha simulation with a corresponding increase in GM-CSF mRNA expression. The enhancement of GM-CSF production by TNF-alpha in myofibroblasts was blocked by the inhibition of RNA synthesis. Prednisolone abolished the GM-CSF production. This study provides evidence for the role of bronchial myofibroblasts in the regulation of inflammatory cell recruitment and activation by interaction in the cytokine network in the bronchial mucosa.
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PMID:Cytokine production by cell cultures from bronchial subepithelial myofibroblasts. 894 23

Bone marrow microvascular endothelial cells (BMEC) are a functional component of the bone marrow stroma and have been shown to release hematopoietic regulatory factors as well as to selectively adhere and support the proliferation and differentiation of CD34+ hematopoietic progenitors. An early passage of these cells was immortalized by transfection with a vector (pSVT) encoding the large T antigen of SV40. The transformed cell line (CDC/CU.BMEC-1) expresses the SV40 transcript, retains the primary cell expression of Ulex europeaus and vWF/ FVIII, and incorporates acetylated low-density lipoprotein. In addition, BMEC-1 mirrors the phenotype of the primary cells with only a few exceptions. Both cell populations express the cellular adhesion molecules ICAM-1 and PECAM and also VCAM-1 and ELAM-1 after upregulation by tumor necrosis factor-alpha. The fibronectin receptor, hyaluronate receptor, collagen receptor, integrins VLA-alpha 3, VLA-alpha 4, and beta 4, endoglin, collagen IV, CD58, and CD61 are also expressed. The only differences are that BMEC-1 expresses higher levels of ICAM-1, CD58, CD34, CD36, and c-kit than the primary cells. The supernatants of primary cell and BMEC-1 contain stem cell factor, interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 alpha, IL-11, and G-CSF. The functional significance of these hematopoietic cytokines was demonstrated in transwell cultures. Both cell populations supported the expansion of progeny from CD34+ cell-enriched cord blood mononuclear cells suspended in the upper chamber. These characteristics, plus the fact that BMEC-1 can be maintained independently of exogenous growth factors and exhibit contact inhibition, indicate that this cell line can be used to further define the role of BMEC in hematopoiesis.
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PMID:BMEC-1: a human bone marrow microvascular endothelial cell line with primary cell characteristics. 895 64

We examined the effects of interferon-gamma (IFN-gamma) on 100% pure human mast cells generated in suspension cultures of umbilical cord blood mononuclear cells in the presence of stem cell factor (SCF) and interleukin-6 (IL-6). When mast cells were suspended in serum-free medium without any cytokine after the withdrawal of SCF and IL-6, they died over a period of 5 days because of apoptosis. IFN-gamma in the cultures suppressed apoptosis and prolonged their survival in a dose-dependent manner. This survival-promoting effect of IFN-gamma was blocked by neutralizing antibodies to IFN-gamma or to IFN-gamma receptor (IFN-gamma R). When mast cells were incubated with IFN-gamma in serum-free medium for more than 4 hr during sensitization, immunoglobulin E (IgE)/anti-IgE antibody-induced histamine release was effectively enhanced. Polymerase chain reaction (PCR) amplification of the alpha-chain of IFN-gamma R (IFN-gamma R alpha) yielded products of the correct size predicted from the sequence of the receptor. In addition, flow cytometry using anti-IFN-gamma R monoclonal antibodies (mAbs) indicated that these mast cells bear IFN-gamma R on their surface. These findings suggested that IFN-gamma activates human mast cells via specific receptors in certain aspects of inflammatory reactions.
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PMID:Interferon-gamma promotes the survival and Fc epsilon RI-mediated histamine release in cultured human mast cells. 901 19


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