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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammalian hemopoiesis results from a complex interaction between hemopoietic progenitor cells, stromal cells and extracellular matrix components, orchestrated by specific glycoprotein growth factors. Recently, these growth factors have been shown to possess an important function, apart from stimulation of proliferation, and that is suppression of an active cellular process of programmed cell death, or apoptosis. Highly specific biochemical and morphologic changes have been shown to occur during apoptosis, but their reflections on cellular functions are poorly understood. Interleukin-3 (IL-3)-dependent FDCP-1 (factor-dependent cell lines cloned in Paterson Laboratories) cells were studied for their ability to adhere to hemopoietic stroma in a temporal fashion under conditions of apoptosis and following rescue from apoptosis with growth factor. It was found that cloned FDCP-1 cells always maintained, in the presence of a source of IL-3 (either WEHI conditioned medium or rm-IL-3), bound cloned hemopoietic stromal cell GB1/6 in a constant fashion for 20 hours, while cells starved of IL-3 experienced a 50% time-dependent decrement in binding. If IL-3 were added back to FDCP-1 that had been starved of growth factor for 8 hours, but not 12 hours, adherence to stroma was restored to that of control cells always in the presence of IL-3. Granulocyte/macrophage colony-stimulating factor (GM-CSF), Interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) did not restore cytoadherence. By transmission electron microscopy, nucleus and cytoplasm of IL-3-replenished cells resembled that of control cells. These data indicate that at least some events related to apoptosis were reversible for a period up to 8 hours, but not 12 hours, in cells that had been rescued by readdition of IL-3. These findings offer important insight into a way in which bone marrow progenitor cells may be maintained in a condition that optimizes their ability to engraft stroma during transplantation.
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PMID:Restorative effect of IL-3 on adherence of cloned hemopoietic progenitor cell to stromal cell. 841 60

Fibroblasts may play an important role in the modulation of immune and inflammatory responses through elaboration of cytokines. To test this hypothesis, human lung fibroblasts were isolated from transbronchial biopsy specimens and assayed for production of interleukin-6 (IL-6) and granulocyte/macrophage colony-stimulating factor (GM-CSF). The sources of fibroblasts included lung allografts, recipient lungs obtained at time of transplant, and normal lung tissue removed during tumor resection. During the course of these studies, several early-passage fibroblasts from transplant recipients were observed to contain mycoplasma (MP)-like organisms as detected by extranuclear fluorescent staining with Hoechst 33258. Positive staining cultures were associated with isolation of Mycoplasma fermentans. IL-6 and GM-GSF as measured by ELISA were found to be elevated over 50-fold in conditioned medium from MP-infected fibroblasts as compared with noninfected lines. Treatment of cells with mycoplasma removal agent (MRA) eliminated extranuclear Hoechst fluorescence and significantly reduced the production of these cytokines. Tumor necrosis factor-beta (TNF-beta) induction of IL-6 and GM-CSF was amplified synergistically in infected cultures. No additional production of IL-6 or GM-CSF was observed in infected cultures treated with interferon-gamma (IFN-gamma) despite the ability of IFN-gamma to modestly induce IL-6 in uninfected cultures. Thus, in vitro infection of lung fibroblasts with MP represents a potent stimulus for the production of inflammatory cytokines and, therefore, necessitates rigorous control for these organisms in cell culture studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced secretion of immune-modulating cytokines by human lung fibroblasts during in vitro infection with Mycoplasma fermentans. 847 29

In this study we evaluated the effect of human immunodeficiency virus type 1 (HIV-1) recombinant tat-protein on the production of interleukin-6 (IL-6), granulocyte/macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) by purified peripheral blood monocytes. Whereas no effects were observed on TNF-alpha and GM-CSF production, recombinant tat-protein was able to induce the production of IL-6 by peripheral blood monocytes in a dose-dependent fashion for concentrations ranging from 1 ng/ml to 1 micrograms/ml. Pre-exposure of tat-protein with a polyclonal neutralizing anti-tat antibody (dilution 1:100) completely abrogated the tat-dependent increase in IL-6 production. The ability of tat-protein to selectively stimulate the production of IL-6 by peripheral blood monocytes could help to explain the presence of elevated levels of IL-6 in the serum of HIV-1 seropositive individuals, especially in patients in advanced stages of the disease with an active viral replication.
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PMID:Human immunodeficiency virus type 1 (HIV-1) tat-protein stimulates the production of interleukin-6 (IL-6) by peripheral blood monocytes. 851 May 64

Embryonic hematopoiesis is initiated in part in the blood islands of the yolk sac. Previous confocal microscopic analysis has shown that the CD34 antigen, a mucin-like cell surface glycoprotein that is expressed by hematopoietic progenitors and all endothelial cells of the adult and embryo, is also found on a subset of luminal hematopoietic-like cells in the yolk sac blood islands as well as on the vascular endothelium lining these early hematopoietic locations. We show here that, as in all other hematopoietic sites thus far examined, immunoaffinity-purified CD34+ nonadherent cells from murine yolk sacs contain the vast majority of erythroid and myeloid progenitor cell colony forming activity. To examine the developmental interactions between these CD34+ hematopoietic progenitor cells of the yolk sac and the CD34+ yolk sac endothelium, we have immunaffinity-purified adherent endothelial cells from day 10.5 yolk sacs using CD34 antiserum and produced cell lines by transformation with a retrovirus expressing the polyoma middle T antigen. Analysis of these cell lines for CD34, von Willebrand's factor, FLK 1 and FLT 1 expression, and capillary growth in Matrigel indicates that they appear to be endothelial cells, consistent with their original phenotype in vivo. Coculture of yolk sac CD34+ hematopoietic cells on these endothelial cell lines results in up to a 60-fold increase in total hematopoietic cell number after approximately 8 days. Analysis of these expanded hematopoietic cells showed that the majority were of the monocyte/macrophage lineage. In addition, examination of the cultures showed the rapid formation of numerous cobblestone areas, a previously described morphologic entity thought to be representative of early pluripotential stem cells. Scrutiny of the ability of these endothelial cell lines to expand committed progenitor cells showed up to a sixfold increase in erythroid and myeloid colony-forming cells after 3 to 6 days in culture, consistent with the notion that these embryonic endothelial cells mediate the expansion of these precursor cells. Polymerase chain reaction analyses showed that most of the cell lines produce FLK-2/FLT-3 ligand, stem cell factor, macrophage colony-stimulating factor, leukemia-inhibitory factor, and interleukin-6 (IL-6), whereas there is a generally low or not measurable production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IL-1, IL-3, transforming growth factor beta-1, erythropoietin, or thrombopoietin. The output of mature hematopoietic cells from these cocultures can be modified to include an erythroid population by the addition of exogenous erythropoietin. These data suggest that endothelial cell lines derived form the yolk sac provide an appropriate hematopoietic environment for the expansion and differentiation of yolk sac progenitor cells into at least the myeloid and erythroid lineages.
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PMID:CD34+ endothelial cell lines derived from murine yolk sac induce the proliferation and differentiation of yolk sac CD34+ hematopoietic progenitors. 854 34

Cytokines, a group of proteins known to regulate hemopoietic and immune functions, are also involved in inflammation, angiogenesis, and bone and cartilage metabolism. Since all of these processes occur following bone injury, or are known to contribute to wound repair mechanisms, this investigation sought to test the hypothesis that cytokines are involved in fracture healing. Two sets of 60 male Sprague-Dawley rats underwent the production of standard closed femoral fractures. The animals were then euthanized in groups of 15 on days 3, 7, 14, and 21 postfracture. A separate control group was also used for the harvesting of intact unfractured bone. At the time of euthanasia, calluses or bone specimens were explanted to organ culture and treated with either media alone or media containing the inducing agents lipopolysaccharide or concanavalin A. A titration of conditioned medium from these cultures was then added to factor-dependent clonal cell lines that are known to be specifically responsive to interleukin-1, interleukin-6, granulocyte-macrophage colony stimulating factor or macrophage-colony stimulating factor. To confirm the identities of each of these cytokines, neutralizing antibody studies were performed. The results showed that interleukin-1 is expressed at very low constitutive levels throughout the period of fracture healing but can be induced to high activities in the early inflammatory phase (day 3). Granulocyte-macrophage colony stimulating factor showed no constitutive activity but could also be induced to high activities with lipopolysaccharide. The ability of these two cytokines to be induced declined progressively as fracture healing proceeded. Interleukin-6 showed high constitutive activity early in the healing process (day 3), and treatment with inducing agent did not increase the activity of this cytokine at this timepoint. Lipopolysaccharide did increase interleukin-6 activity in day 7 and 14 fracture calluses. Although macrophage-colony stimulating factor is thought to be involved in a variety of metabolic bone conditions, it could not be detected or induced from any of the callus samples. Moreover, none of the samples of unfractured bone showed constitutive or inducible activities for any of these cytokines. A separate experiment in which calluses and samples of unfractured bone from similar cultures were examined histologically and tested for DNA or protein synthesis at two timepoints in the culture period (days 1 and 4) showed that tissue viability was maintained. Thus the inability to detect macrophage colony-stimulating factor in fracture callus or any cytokine activity in unfractured bones was not due to cell death.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The expression of cytokine activity by fracture callus. 858 32

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

STAT proteins are a group of latent cytoplasmic transcription factors which function as signal transducers and activators of transcription. Stat1 and -2 were originally identified to function in interferon signaling, and Stat1 was also found to be activated by epidermal growth factor (EGF) and other cytokines. New members of the STAT gene family are identified. Among them, Stat3 has 52.5% amino acid sequence homology with Stat1 and is activated by platelet-derived growth factor (PDGF), colony-stimulating factor 1 (CSF-1), EGF, interleukin-6, and other cytokines. Treatment of cells with EGF activates Stat1 and Stat3, which become phosphorylated on tyrosine residues to form homo - or heterodimers and translocate into the nucleus, binding to the sis-inducible element (SIE) in the c-fos promoter. Somatic cell genetic analyses demonstrated that Jaks, a family of nontransmembrane protein tyrosine kinases, are required for the activation of Stat1 and Stat2 in interferon-treated cells. However, little is known about the activation of Stat3 by growth factors. Here we report that in all v-Src-transformed cell lines examined, Stat3 is constitutively activated to bind to DNA and the phosphorylation of tyrosine on Stat3 is enhanced by the induction of v-Src expression. We also report that Src is shown to be associated with Stat3 in vivo, as well as in vitro, and phosphorylates Stat3 in vitro. Stat3 is also activated by CSF-1, possibly through CSF-1 receptor-c Src association in NIH 3T3 cells overexpressing CSF-1 receptors. Together, the data suggest that Src is involved in activation of Stat3 in growth factor signal transduction.
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PMID:Activation and association of Stat3 with Src in v-Src-transformed cell lines. 865 34

Normal human polymorphonuclear neutrophils (PMN) undergo rapid apoptosis during in vitro culture. In contrast, apoptosis is inhibited in PMN from patients with severe burns. This inhibition is not an inherent property of the cells but is caused by thermolabile factors present in the plasma. Endotoxin and the proinflammatory cytokines interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) do not appear to be directly responsible. The ability of burn plasma to inhibit apoptosis was reduced by neutralizing antibodies to human granulocyte macrophage colony-stimulating factor (GM-CSF). GM-CSF levels could not be detected in the burn plasma. However, the incubation of burn-derived or normal leukocyte populations consisting primarily of PMN in burn plasma induced the production of GM-CSF. The results suggest that activation of GM-CSF synthesis by factor(s) in burn plasma may play a role in regulating inflammation by the inhibition of apoptosis.
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PMID:Inhibition of apoptosis in polymorphonuclear neutrophils from burn patients. 869 Oct 68

Human peripheral blood leukocytes (hPBL) are a rich source of natural leukocyte interferon (IFN-alpha) when treated with Sendai virus. Sendai virus treatment of hPBL will also result in significant production of several chemokines and cytokines such as macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, RANTES, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8, in a time-dependent way. A significant amount of MCP-1 is constitutively produced in overnight culture of leukocytes. The most abundant cytokine is IFN-alpha, which is induced to its maximum level approximately 11-15 h after addition of Sendai virus. The amount of IFN-alpha induced at 15 h after Sendai virus treatment is more than 16-fold higher than those of MIP-1alpha, MIP-1beta, and RANTES. IFN-alpha is also induced more than 60-fold higher than TNF-alpha and IL-8. The amount of IL-6 induced is approximately 400-fold less than IFN-alpha. Limited amounts of other cytokines such as IL-1alpha, IL-1beta, macrophage colony-stimulating factor, TNF-beta, and IFN-gamma are also induced in Sendai virus-treated hPBL. No measurable amount of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, leukemia inhibitory factor, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-11, or IL-12 was induced in the supernatant of Sendai virus-treated hPBL.
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PMID:Cytokines induced by Sendai virus in human peripheral blood leukocytes. 869 16

Astrocytes produce granulocyte/macrophage colony-stimulating factor (GM-CSF) and support the survival and proliferation of microglia. To study the functions of GM-CSF in the central nervous system (CNS), we examined the effects of GM-CSF on cytokine production by glial cells. GM-CSF induced interleukin-6 (IL-6) production by microglia, but not by astrocytes, in a dose-dependent manner as assessed by bioassay and the detection of IL-6 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. GM-CSF did not induce tumor necrosis factor (TNF) alpha or IL-1 in microglia and astrocytes, whereas lipopolysaccharide induced all these cytokines. The induction of IL-6 by GM-CSF in microglia was completely inhibited by antibodies to GM-CSF. Neither IL-3 nor macrophage-CSF (M-CSF) induced IL-6 production in microglia. Given that IL-1 and TNF alpha, monokines derived from microglia, induce IL-6 production in astrocytes, but not in microglia, results indicate that astrocytes and microglia may mutually regulate IL-6 production by different cytokines.
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PMID:Selective induction of interleukin-6 in mouse microglia by granulocyte-macrophage colony-stimulating factor. 872 91


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