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

Among the molecules that determine the developmental fate of sympathetic neurons from noradrenergic to cholinergic function are two apparently unrelated proteins, cholinergic differentiation factor and ciliary neurotrophic factor (CDF and CNTF, respectively). The present work suggests a structural basis for their functional overlap: sequence pattern-matching and predictive structure analysis contends that CDF and CNTF are homologous and share a common helical framework. An integrated CDF/CNTF profile also reveals similar sequence/structure motifs in a group of hematopoietic cytokines composed of granulocyte colony-stimulating factor, interleukin-6, and a novel factor called oncostatin M; a more distant relationship is indicated with interleukin-3 and interferons-alpha/beta. Evolutionary ties between neuropoietic and hematopoietic cytokines predict a distinctive tertiary architecture for the uncharacterized CDF and CNTF receptors. The intertwined cytokine/receptor networks signal a closer relationship between the molecular mechanisms underlying neuro- and hematopoiesis.
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PMID:Neuropoietic cytokines in the hematopoietic fold. 171 45

Human recombinant interleukin-6 (IL-6) and human recombinant leukemia inhibitory factor (LIF) similarly stimulate synthesis of typical acute-phase proteins in the primary rat hepatocyte cultures. LIF is, however, less effective in increasing uptake of alpha-aminoisobutyric acid than IL-6. Antiserum to human IL-6 abolishes induced protein synthesis and amino acid uptake elicited by hrIL-6 but has no effect on the acute-phase response of rat liver cells stimulated by LIF. Both IL-6 and LIF inhibit basal and epidermal growth factor-induced DNA synthesis in rat hepatocytes.
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PMID:Effects of interleukin-6 and leukemia inhibitory factor on the acute phase response and DNA synthesis in cultured rat hepatocytes. 171 73

The quest for methods to protect cells from the damaging effects of ionizing radiation led to the observation that cytokines, endogenously produced hormone-like polypeptides, are radioprotective. Interleukin-1 and tumor necrosis factor-alpha, given before irradiation, can protect mice from doses of radiation that would be fatal to untreated animals. At lower doses of radiation, the hemopoietic growth factors, interleukin-1, interleukin-4, interleukin-6, tumor necrosis factor-alpha, interferon, and leukemia inhibitory factor can promote recovery when administered after irradiation. Exposure to ionizing radiation selectively induces expression of some cytokines. Recent work suggests that certain cytokines may initiate autocrine/paracrine regulated recovery and repair pathways. Thus, the radioprotective and therapeutic effects of supplementary pharmacological doses of cytokines may act by amplifying innate defenses to ionizing radiation.
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PMID:Radioprotection with cytokines--learning from nature to cope with radiation damage. 176 Feb 47

Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), two multifunctional cytokines, recently have been identified as physiological inducers of hematopoietic cell differentiation which also induce terminal differentiation and growth arrest of the myeloblastic leukemic M1 cell line. In this work, it is shown that c-myc exhibited a unique pattern of expression upon induction of M1 terminal differentiation by LIF or IL-6, with an early transient increase followed by a decrease to control levels by 12 h and no detectable c-myc mRNA by 1 day; in contrast, c-myb expression was rapidly suppressed, with no detectable c-myb mRNA by 12 h. Vectors containing the c-myc gene under control of the beta-actin gene promoter were transfected into M1 cells to obtain M1myc cell lines which constitutively synthesized c-myc. Deregulated and continued expression of c-myc blocked terminal differentiation induced by IL-6 or LIF at an intermediate stage in the progression from immature blasts to mature macrophages, precisely at the point in time when c-myc is normally suppressed, leading to intermediate-stage myeloid cells which continued to proliferate in the absence of c-myb expression.
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PMID:Interleukin-6- and leukemia inhibitory factor-induced terminal differentiation of myeloid leukemia cells is blocked at an intermediate stage by constitutive c-myc. 190 40

Significant stimulation of growth of myoblasts in culture is achieved by leukemia inhibitory factor (LIF). The optimum activity of this cytokine occurs at about 6 pM LIF. Interleukin-6 (IL-6) also stimulates cultured myoblasts but to a lesser degree than LIF and the effect is not maintained for extended culture periods. In addition, transforming growth factor-alpha (TGF-alpha) also increases the growth rate of myoblasts but only after a considerable lag phase. All 3 cytokines may be of value in the large scale production of myoblasts for use in the potential treatment of primary myopathies by injection of cultured myoblasts into diseased muscle to form genetically complete muscle fibres after fusion of the myoblasts in situ. Their potential use is enhanced in that at least under the conditions used here they do not stimulate fibroblast proliferation.
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PMID:Stimulation of myoblast proliferation in culture by leukaemia inhibitory factor and other cytokines. 190 37

The notion that a single hormone may exert a broad range of effects has become well established. As such, leukemia inhibitory factor (LIF) is a prime example. LIF was initially described, purified, and genetically cloned on the basis of its ability to induce the differentiation and suppress the clonogenicity of the monocytic leukemia cell line, M1. Subsequently, it has become apparent that in vitro LIF inhibits the differentiation of pluripotential ES cells, stimulates the synthesis of hepatic acute-phase proteins, induces a switch in neurotransmitter phenotype from adrenergic to cholinergic, suppresses adipocyte lipoprotein lipase activity, and results in an increase in bone resorption. Moreover, elevation of LIF levels in vivo has a number of patho-physiological consequences, many of which parallel those effects observed in vitro. The challenge that lies ahead is to determine whether other sites of LIF action exist and to define more clearly the physiological role LIF plays in vivo. A major mechanism of cell-cell communication is by the production and secretion of polypeptide hormones by one cell type, which act either systemically or locally, via interaction with specific receptors on the surface of responsive cells. Recently, it has become apparent that hormones initially described and named, on the basis of a specific action, in many cases exert a spectrum of effects on a broad range of cell types. Moreover, the effects exerted are often mimicked closely by other hormones. Hormones that act in a pleiotropic manner are, for example, transforming growth factor-beta (TGF-beta), the various fibroblast growth factors (FGFs), interleukin-6 (IL-6), and leukemia inhibitory factor (LIF). This review will focus on the various biological effects ascribed to LIF.
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PMID:Leukemia inhibitory factor: a biological perspective. 190 73

An elucidation of the interaction between the bone marrow microenvironment and hematopoietic stem cells is critical to the understanding of the molecular basis of stem cell self renewal and differentiation. This interaction is dependent, at least in part, on direct cell to cell contact or cellular adhesion to extracellular matrix proteins. Long-term bone marrow cultures (LTMC) provide an appropriate microenvironment for maintenance of primitive hematopoietic stem cells and a means of analyzing this stem cell-stromal cell interaction in vitro. Although LTMC have been successfully generated from murine and human bone marrow, only limited success has been reported in a primate system. In addition, few permanent stromal cell lines are available from nonmurine bone marrow. Because the primate has become a useful model for large animal bone marrow transplant studies and, more specifically, retroviral-mediated gene transfer analysis, we have generated immortalized bone marrow stromal cell lines from primate bone marrow using gene transfer of the Simian virus large T (SV40 LT) antigen. At least one stromal cell line has demonstrated the capacity to maintain early hematopoietic cells in long-term cultures for up to 4 weeks as measured by in vitro progenitor assays. Studies were undertaken to characterize the products of extracellular matrix biosynthesis and growth factor synthesis of this cell line, designated PU-34. In contrast to most murine bone marrow-derived stromal cell lines capable of supporting hematopoiesis in vitro that have been examined, the extracellular matrix produced by this primate cell line includes collagen types I, laminin. Growth factor production analyzed through RNA blot analysis, bone marrow cell culture data, and factor-dependent cell line proliferation assays includes interleukin-6 (IL-6), IL-7, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, leukemia inhibitory factor, and a novel cytokine designated IL-11. This immortalized primate bone marrow stromal cell line may be useful in maintaining early progenitor cells for experimental manipulation without the loss of reconstituting capacity and as a potential source of novel hematopoietic growth factors.
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PMID:Stromal cell-associated hematopoiesis: immortalization and characterization of a primate bone marrow-derived stromal cell line. 201 98

We have investigated the role that hemopoietic regulatory molecules may play in mouse embryogenesis prior to the appearance of hemopoietic stem cells or their microenvironments. Using polymerase chain reaction analysis, we detected mRNA transcripts for interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) but not for granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3 in mouse blastocysts at 3.5 days of gestation. Functional IL-6 protein was also detected in cultured blastocysts as a secreted product, as was an activity consistent with the presence of LIF protein. The expression of IL-6 and LIF in blastocysts prior to hemopoiesis suggests that these proteins may regulate the growth and development of trophoblasts or embryonic stem cells.
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PMID:The genes for leukemia inhibitory factor and interleukin-6 are expressed in mouse blastocysts prior to the onset of hemopoiesis. 211 4

This study examines the effect of leukemia inhibitory factor (LIF) on preosteoblastic rat calvaria (RCT-1) cells, which acquire osteoblastic properties when treated with retinoic acid (RA). LIF potentiated the increase in alkaline phosphatase (AP) activity produced by RA. The LIF effect was time and dose dependent (EC50, approximately 1 pM). The earliest effects on AP activity were detected at 48 h, and maximal effects were observed after 72 h. RA increased AP mRNA about 2-fold at 3 h and 6-fold at 6 and 12 h. LIF further increased AP mRNA to 18-fold at 12 h. After RA treatment AP mRNA returned to control levels at 24 h, but in the presence of LIF, AP mRNA remained elevated at 24 and 72 h of treatment. When given alone, LIF had no effect on either AP activity or mRNA levels. Tumor necrosis factor-alpha and 1,25-dihydroxyvitamin D3 also potentiated the RA induction of AP, and interleukin-6 had a small effect, whereas granulocyte macrophage colony-stimulating factor had no effect. LIF alone had a small inhibitory effect on type 1 collagen mRNA, but did not oppose the stimulatory effect of RA. Consistent with these biological actions, LIF receptors were demonstrated on these cells. [125I]LIF bound to RCT-1 cells at 0 C with an apparent dissociation constant of 20 pM, and it was found that these cells express an average of 300 receptors/cell. Scatchard analyses showed a single class of high affinity binding site. LIF was internalized with an endocytic rate constant for occupied receptors of 0.03 min-1, and the apparent equilibrium dissociation constant at 37 C was 358 pM. These findings suggest that osteoblast precursor cells are among the target cells of LIF.
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PMID:Leukemia inhibitory factor binds with high affinity to preosteoblastic RCT-1 cells and potentiates the retinoic acid induction of alkaline phosphatase. 211 91

The viability of normal bone marrow myeloid precursor cells induced by interleukin-6 (IL-6) or IL-1 alpha and the ability of IL-6 and IL-1 alpha to induce the formation of colonies of granulocytes, macrophages, or megakaryocytes in densely seeded bone marrow cultures was suppressed by transforming growth factor-beta 1 (TGF-beta 1). Induction of normal bone marrow colony formation by IL-3 was much less sensitive to TGF-beta 1, and there was little or no effect of TGF-beta 1 on colony formation induced by macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF). In different clones of myeloid leukemic cells, TGF-beta 1 suppressed differentiation induced with IL-6, IL-1 alpha, or lipopolysaccharide (LPS), but did not suppress differentiation induced with IL-3 or GM-CSF. The effect of TGF-beta 1 on differentiation of the leukemic cells can be dissociated from its effect on cell growth. TGF-beta 1 suppressed the production of IL-6 in normal bone marrow cells cultured with IL-1 alpha and the production of IL-6 and GM-CSF in leukemic cells cultured with IL-1 alpha or LPS. The suppression of IL-6 production can explain the suppression by TGF-beta 1 of the effects of IL-1 alpha and LPS that are mediated by IL-6. TGF-beta 1 also suppressed differentiation in clones of myeloid leukemic cells induced with differentiation factor/leukemia inhibitory factor and tumor necrosis factor. In different leukemic clones TGF-beta 1 suppressed or enhanced induction of differentiation with dexamethasone. The results show that TGF-beta 1 can selectively control the activity of different molecular regulators of normal and leukemic hematopoiesis.
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PMID:Selective regulation of the activity of different hematopoietic regulatory proteins by transforming growth factor beta 1 in normal and leukemic myeloid cells. 220 8


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