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)

Under strict observation of the ethical guidelines of the 1975 Declaration of Helsinki Human Research Committee, primary hepatocyte cultures were prepared from second-trimester fetal liver specimens. We have shown for the first time that fetal hepatocytes have the capacity to produce an acute-phase response on treatment with inflammatory mediators. Addition of interleukin-6 to the cultures resulted in strong induction of C-reactive protein and alpha-1-antichymotrypsin expression, whereas albumin expression was repressed. In contrast to interleukin-6, transforming growth factor-beta did not induce C-reactive protein expression. However, as in adult hepatocytes, fetal cells responded to transforming growth factor-beta by reduced albumin synthesis. We were able to show by virtue of fluorescein excretion into sealed clefts that fetal hepatocytes have the functional capacity to form bile. Our findings indicate that second-trimester hepatocytes can be regarded as fairly mature liver cells.
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PMID:Human fetal hepatocytes respond to inflammatory mediators and excrete bile. 171 Oct 3

Using a transforming growth factor-beta (TGF beta)-sensitive cell line, Mv1Lu (or CCL 64), we demonstrated that trophoblasts predominantly produced a latent form of TGF beta. After converting latent TGF beta to active TGF beta in vitro by acid (pH 2.5), alkali (pH 10.0), or heat (90 C; 10 min) treatment, addition of rabbit anti-TGF beta 1 antiserum resulted in the elimination of TGF beta activity, thus suggesting that trophoblasts produced at least a certain amount of latent TGF beta 1. To investigate the role of TGF beta 1 in placental hormonogenesis, we first studied the effect of recombinant (r) TGF beta 1 on the production of interleukin-6 (IL-6) and hCG by trophoblasts. rTGF beta 1 exerted no inhibitory activity on IL-6 and hCG production. The effect of rTGF beta 1 on cytokine-induced IL-6 and hCG release was then examined. While rTGF beta 1 failed to inhibit basal hCG secretion, it did inhibit recombinant tumor necrosis factor-alpha (rTNF alpha)-induced IL-6 release as well as rTNF alpha- and rIL-6-induced hCG release in a dose-dependent manner. However, rIL-1 alpha-induced IL-6 and hCG release was remarkably sensitive to rTGF beta 1-mediated suppression. In contrast, GnRH-induced hCG release, the response of which is independent of the IL-6 and IL-6 receptor system in trophoblasts, was completely resistant to rTGF beta 1. Thus, trophoblast-derived TGF beta 1 is an important regulatory molecule of cytokine-dependent, but not cytokine-independent, hCG release, possibly by converting latent TGF beta to active TGF beta at the local site of trophoblasts.
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PMID:Trophoblast-derived transforming growth factor-beta 1 suppresses cytokine-induced, but not gonadotropin-releasing hormone-induced, release of human chorionic gonadotropin by normal human trophoblasts. 172 23

Liver fat-storing cells (FSC) play an important role in collagen deposition. During the induction of liver cirrhosis, FSC lose their fat droplets, acquire an actin-rich cytoskeleton and transform into myofibroblasts. Myofibroblasts have been associated with increased collagen production in cirrhotic livers. Cultured FSC resemble myofibroblasts. However, it is not known whether regulation of collagen gene expression is similar in FSC obtained from normal or cirrhotic livers. In this communication, we describe the characterization of two fat-storing cell lines, one from normal (NFSC) and one from CCl4-cirrhotic liver (CFSC), obtained after spontaneous immortalization in culture. We studied the effect of serum and various growth factors on cell proliferation. We determined the production of collagen and fibronectin and we analyzed the presence of mRNA transcripts of collagens type I, III, and IV, fibronectin laminin, transforming growth factor-beta and interleukin-6. We found that CFSC have a greater serum-dependency than NFSC. NFSC grow with a mixture of insulin and epidermal growth factor, whereas CFSC proliferate only with platelet-derived growth factor. Although we did not find significant differences in the expression of mRNAs for collagen type I, fibronectin and transforming growth factor-beta, collagen and fibronectin synthesis was increased 2- and 1.5-fold respectively. NFSC contained 1.6- and 2.0-fold more type III collagen and laminin mRNAs, respectively, than CFSC. Neither cell line expressed type IV collagen mRNA. NFSC but not CFSC produced interleukin-6. These results suggest that, except for the lack of transcripts of collagen type IV, both cell lines resemble primary cultures of FSC. However, significant differences in cell proliferation and interleukin-6 production between the two cell lines were found. We suggest that these cell lines could be useful tools to study possible differences in regulation of matrix production by FSC.
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PMID:Characterization of fat-storing cell lines derived from normal and CCl4-cirrhotic livers. Differences in the production of interleukin-6. 175 10

PL-21 is a promyelocytic leukemia cell line that produces plasminogen activator inhibitor 2 (PAI-2). Differentiation-linked expression of PAI-2 was investigated by adding cell-differentiation promoting agents [such as phorbol myristate acetate (PMA), retinoic acid (RA), dexamethasone (Dex), and recombinant cytokines, including tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), granulocyte-colony stimulating factor (G-CSF), and interleukin-6 (IL-6)] into the culture medium of PL-21 cells. PAI-1 and PAI-2 antigens were measured by an enzyme-linked immunoassay. The PAI-1 antigen, however, became detectable only after stimulation. The presence of PAI-2 antigen was further verified by immunoblotting using a monoclonal antibody against PAI-2 purified from a PL-21 culture medium. PAI activity both in the culture medium and in the cell lysate increased approximately 70-fold after exposure to PMA. Both PAI-1 and PAI-2 antigens increased, but the amount of the latter in the culture medium and in the cell lysate was approximately 10 times and 2,500 times, as much, respectively, as that of the former. Dex also increased the intracellular PAI activity approximately 6-fold, parallel with PAI-2 antigen. PAI-1 antigen increased only slightly in the culture medium but not in the cell lysate after Dex-stimulation. As with the case of PMA, TNF-alpha and IL-6 induced PL-21 cells to macrophage-like cells, but did not affect the PAI activity. Thus, the increase of the PAI-2 production by PMA may not necessarily depend on differentiation into macrophages. Other cytokines examined did not increase the PAI activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dexamethasone and phorbol ester, but not cytokines, increase the production of plasminogen activator inhibitor type-2 in the PL-21 human promyelocytic leukemia cell line. 177 17

Differentiation-linked expression of plasminogen activator inhibitor-2 (PAI-2) was investigated by adding cell-differentiation promoting agents [such as phorbol myristate acetate (PMA), retinoic acid, dexamethasone (Dex), and recombinant cytokines, including tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta, granulocyte-colony stimulating factor, and interleukin-6 (IL-6)] into the culture medium of a promyelocytic leukemia cell line PL-21. PAI activity both in the culture medium and in the cell lysate increased approximately 70-fold after exposure to PMA. Both PAI-1 and PAI-2 antigens increased, but the amounts of the latter in the culture medium and in the cell lysate were approximately 10 times and 2,500 times, as much, respectively, as those of the former. Dex also increased the intracellular PAI activity approximately 6-fold, parallel with PAI-2 antigen. PAI-1 antigen increased only slightly in the culture medium but not in the cell lysate after Dex-stimulation. As with the case of PMA, TNF-alpha and IL-6 induced PL-21 cells to macrophage-like cells, but did not affect the PAI activity. Thus, the increase of the PAI-2 production by PMA may not necessarily depend on differentiation into macrophages. Other cytokines examined did not increase the PAI activity. PAI-2 antigen was demonstrated in the cell lysates of various leukemia cells by Western blotting technique using a monoclonal antibody against the PAI-2 purified from PL-21 culture medium. PAI-2 antigen was frequently detected in the plasmas from the patients whose peripheral leukocytes were more than 10,000/microliters.
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PMID:[Production and secretion of the plasminogen activator inhibitor type-2 in a leukemia cell line]. 187 Feb 66

We investigated the effects of several cytokines on HLA-DR expression in cultured fibroblasts derived from retroocular connective tissue and pretibial and abdominal skin of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD), as well as from normal individuals. We hypothesized that differences in response to cytokines between fibroblasts from various anatomical areas might play a role in the site-selective involvement of the extrathyroidal manifestations of Graves' disease. HLA-DR expression in fibroblasts was quantitated by scanning densitometry of whole cell lysates subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Direct immunofluorescence of cell monolayers was also performed. We hypothesize that unique characteristics of these fibroblasts may play a role in GO and PTD. Cultured retroocular, pretibial, and abdominal fibroblasts from patients with Graves' disease as well as from normal individuals did not express HLA-DR spontaneously. Treatment in vitro with interferon-gamma (IFN gamma; 100 U/mL) for 5 days induced HLA-DR by 50- to 80-fold (P less than 0.0001) in fibroblasts from all sites and subjects studied. However, IFN gamma-induced HLA-DR expression was significantly greater in retroocular (P less than 0.005) and pretibial (P less than 0.0005) fibroblasts from patients with GO and PTD than in fibroblasts obtained from the same anatomical sites of normal individuals. Further, retroocular and pretibial fibroblasts from patients with GO and PTD responded to IFN gamma more vigorously than did abdominal fibroblasts from these same patients (P less than 0.0001). IFN gamma-induced HLA-DR expression was enhanced by concomitant treatment with tumor necrosis factor-alpha (100 U/mL). In contrast, treatment of retroocular fibroblasts with transforming growth factor-beta (10 ng/mL), epidermal growth factor (1 ng/mL), or interleukin-6 (IL-6; 100 U/mL) significantly attenuated IFN gamma-induced HLA-DR reactivity by 40-59% (P less than 0.05). Incubation of retroocular fibroblasts with tumor necrosis factor-alpha, IL-1 alpha (10 U/mL), IL-2 (10 U/mL), IL-6, granulocyte-macrophage colony-stimulating factor (100 U/mL), epidermal growth factor, and transforming growth factor-beta alone did not affect HLA-DR expression. These results indicate that several cytokines can influence HLA-DR expression in cultured fibroblasts. The enhanced induction of HLA-DR by IFN gamma in retroocular and pretibial fibroblasts compared with that in abdominal fibroblasts may partially explain the selective involvement of the retroocular connective tissue and pretibial skin in fully expressed Graves disease.
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PMID:Increased induction of HLA-DR by interferon-gamma in cultured fibroblasts derived from patients with Graves' ophthalmopathy and pretibial dermopathy. 190 94

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

Data concerning megakaryocytopoiesis and its regulation were summarized in this report. Critical analysis of these data indicates that: (i) megakaryocytopoiesis is a complex, multiple-stage cellular and biologic process; (ii) the survival, proliferation and differentiation of progenitor cells into immature megakaryocytes are regulated mainly by interleukin-3, granulocyte-macrophage colony-stimulating factor and an as yet uncharacterized megakaryocyte colony-stimulating factor, and the maturation of immature megakaryocytes to produce platelets is regulated primarily by interleukin-6 and thrombopoietin; (iii) optimal megakaryocyte development needs adequate interactions of several growth factors with target cell population and hematopoietic microenvironment; (iv) megakaryocytopoietic inhibition is controlled essentially by megakaryocyte-platelet products such as transforming growth factor-beta, and platelet factor 4 and its related proteins; interferon-alpha and -gamma also are able to play an inhibitory role; and (v) expansion or decrease of either normal or neoplastic megakaryocyte progenitor cells, change of platelet mass and abnormalities of growth factor levels in hematopoietic tissue might result in an abnormal megakaryocytopoiesis.
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PMID:Megakaryocytopoiesis: characterization and regulation in normal and pathologic states. 195 49

Cultured human keratinocytes and squamous cell carcinoma (SCC) cell lines were analyzed for the presence of ribonucleic acid (RNA) transcripts for the cytokines interleukin-1 and interleukin-6 and for these proteins. This study demonstrates that both cytokines are synthesized and secreted by both normal keratinocytes and SCC lines. The rate of secretion of these cytokines can be augmented in response to a variety of stimuli including tumor necrosis factor-alpha, granulocyte-macrophage colony stimulating factor, transforming growth factor-beta and the combination of lipopolysaccharide and phorbol myristate acetate. Interleukin-1 and interleukin-6 have been reported to influence the proliferation of cultured human fibroblasts. However, these cytokines had no significant effect on the proliferation of human keratinocytes or the SCC lines tested. Although it seems unlikely that interleukin-1 or interleukin-6 could directly influence keratinocyte proliferation in vivo, the capacity of these cells to synthesize and release these cytokines supports earlier observations that keratinocytes may play an important role in augmenting an immune or inflammatory response.
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PMID:Production of interleukin-1 and interleukin-6 by human keratinocytes and squamous cell carcinoma cell lines. 202 85

Communication between cells determines the steady-state composition of the lung in health and becomes a critical determinant of outcome in pathologic processes resulting in anatomic remodeling. This review presents the evolving concepts of the biology of cytokines (also known as peptide growth factors or biological response modifiers) in maintaining normal tissue growth and homeostasis. How these extracellular signaling proteins are involved in such pathologic disorders as spontaneous pulmonary fibrosis, sarcoidosis, pneumoconiosis, and the evolution and recovery from acute lung injury is also discussed. During the past decade the cytokines have come to the fore as important multifunctional mediators of cell behavior and cell-cell communication. A wide range of cellular responses are influenced or triggered when cytokines interact with cells. These include mitosis, chemotaxis, angiogenesis, cytoskeleton arrangement, immunomodulation, and extracellular matrix production. Cytokines influence cell behavior by binding to specific high affinity surface receptors on target cells. These receptors are linked in turn at the cell membrane to a complex array of intracellular signaling pathways. Individual cytokines may inhibit as well as promote cellular functions such as mitosis and thereby play a critical role in homeostasis of normal tissue elements. Hence, cytokines are intimately involved in normal tissue homeostasis as well as in processes eventuating in growth and remodeling. All cells produce and secrete cytokines at some time during their life. Each cytokine is capable of modulating more than one cellular function. Although produced by a variety of cell types, the triggers that induce a specific cytokine to be produced differ between cells. Many of the cytokines share regions of homologous nucleic acid sequences, suggesting that they are members of larger gene families. Given that tissues and cells are exposed to complex cytokine mixtures rather than to individual cytokines, recent attention has turned to understanding how cytokines interact. The combined effects of cytokine mixtures have proved to be both complex and unpredictable based on knowledge of the separate actions of the individual cytokines involved. In studies of the role of cytokines in lung disease, early research attention has focused on those cytokines released by alveolar macrophages (the so-called macrophage-derived growth factors). However, structural cells as well as immune effector cells of the lung are capable of cytokine production and release. The cytokines receiving the most attention to date in relation to pulmonary diseases include platelet-derived growth factor (PDGF), interleukin-1 (IL-1), transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), insulinlike growth factor I (IGF-I), and, most recently, interleukin-6 (IL-6).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytokines of the lung. 224 Aug 51


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