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

Ciliary neurotrophic factor (CNTF) has recently been found to share receptor components with, and to be structurally related to, a family of broadly acting cytokines, including interleukin-6, leukemia inhibitory factor, and oncostatin M. However, the CNTF receptor complex also includes a CNTF-specific component known as CNTF receptor alpha (CNTFR alpha). Here we describe the molecular cloning of the human and mouse genes encoding CNTFR. We report that the human and mouse genes have an identical intron-exon structure that correlates well with the domain structure of CNTFR alpha. That is, the signal peptide and the immunoglobulin-like domain are each encoded by single exons, the cytokine receptor-like domain is distributed among 4 exons, and the C-terminal glycosyl phosphatidylinositol recognition domain is encoded by the final coding exon. The position of the introns within the cytokine receptor-like domain corresponds to those found in other members of the cytokine receptor superfamily. Confirming a recent study using radiation hybrids, we have also mapped the human CNTFR gene to chromosome band 9p13 and the mouse gene to a syntenic region of chromosome 4.
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PMID:Genomic organization and chromosomal localization of the human and mouse genes encoding the alpha receptor component for ciliary neurotrophic factor. 777 13

Animal study results have suggested a role in sepsis for human interleukin for DA1.a cells/leukemia inhibitory factor (HILDA/LIF). HILDA/LIF and interleukin-6 (IL-6) levels were prospectively studied by serial ELISAs in 34 septic patients. HILDA/LIF was detected in 11 of 34 patients at plasma levels of 100-37,000 pg/mL. Peak HILDA/LIF levels correlated with increased temperature and creatinine and IL-6 and with decreased arterial CO2 (P < .05). Multivariate analysis showed that shock and decreased arterial CO2 accounted for 75% of peak HILDA/LIF plasma variations (R2 = .753). Fatal outcome was most often associated with detectable HILDA/LIF (> 56 pg/mL) and peak IL-6 plasma levels > 850 pg/mL (sensitivity, 83%; specificity, 87%), but both (at respective levels of > 480 and > 850 pg/mL) were associated with fatal outcome. HILDA/LIF was detected in septic patients exhibiting shock, and its levels correlated with higher mortality and shorter survival.
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PMID:Increased plasma levels of human interleukin for DA1.a cells/leukemia inhibitory factor in sepsis correlate with shock and poor prognosis. 779 71

Ciliary neurotrophic factor (CNTF) is a 22-kDa protein predicted to share with leukemia inhibitory factor (LIF) and interleukin-6 a common amphipathic helical domain. Consistent with this prediction, the CNTF receptor complex is composed of the CNTF alpha receptor, the LIF beta receptor and gp130 a signalling molecule for LIF and interleukin-6. The major sources of synthesis of CNTF are Schwann cells and astrocytes, but it remains unclear how much CNTF is released from these glial cells and by what mechanism. In vitro, CNTF supports the survival of all classes of peripheral nervous system neurons plus many CNS neurons, induces neurite outgrowth, promotes a cholinergic phenotype in sympathetic neurons and arrests division of neuronal precursor cells. Several cell lines also respond to CNTF. In vivo, CNTF rescues several types of neurons from axotomy-induced death. The functions of CNTF in the development and maintenance of the nervous system remain enigmatic.
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PMID:Ciliary neurotrophic factor: a review. 780 79

The physiologic program of macrophage differentiation normally proceeds in a coordinated manner in response to several different growth factors. Although the utilization of common receptor subunits may explain in part overlapping biologic functions, mechanisms by which unique actions are mediated remain obscure. We examined growth factor-induced macrophage differentiation in M1 leukemia cells that simultaneously display receptors for interleukin-6 (IL-6), leukemia inhibitory factor (LIF) and Oncostatin-M (OSM). Differentiation induced by all three factors was associated with decreased expression of transcription factors myb and SCL, increased expression of macrophage markers, and suppression of proliferation. Cell lines were established in which SCL expression was enforced. In the absence of growth factors, cells were indistinguishable from parental cells. However, LIF (or OSM)-induced macrophage differentiation was perturbed; there was failure to undergo morphologic differentiation, disturbed expression of lysozyme and Mac1 alpha, and failure to suppress proliferation. Surprisingly the perturbation of macrophage differentiation did not apply to induced expression of macrophage colony-stimulating factor (M-CSF) or granulocyte colony stimulating factor (G-CSF) receptors. This dissociation of elements normally coordinated in a macrophage differentiation program applied at a clonal level. There was no disturbance of IL-6-induced macrophage differentiation. These data directly implicate SCL in components of the macrophage differentiation program (suggesting that LIF receptor/gp130 heterodimers utilize an SCL-inhibitable pathway while gp130 homodimers do not) and demonstrate differential-regulation of components of the mature macrophage phenotype.
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PMID:Differential regulation of macrophage differentiation in response to leukemia inhibitory factor/oncostatin-M/interleukin-6: the effect of enforced expression of the SCL transcription factor. 781 94

The aim of this study was to investigate whether mouse placenta produces mature mouse GHRF (mGHRF) and whether cytokines regulate placental mGHRF production. Using Sephadex G-50 gel filtration chromatography and reverse phase HPLC, we identified immunoreactive mGHRF in acid-ethanol extract of placental tissues, which had chromatographic characteristics identical to those of hypothalamic mature mGHRF peptide. The major peak of immunoreactive GHRF in the medium from cultured placental cells was resolved by HPLC at a fraction identical to hypothalamic mature mGHRF. Interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin-M, which all use gp130 as a signal transducer, significantly inhibited mGHRF secretion by cultured placental cells. However, IL-1 alpha and tumor necrosis factor-alpha had no effect on mGHRF secretion. Antibodies to IL-6 or IL-6 receptor completely blocked the inhibitory effect of IL-6 on mGHRF secretion. Anti-LIF, and oncostatin-M inhibited the expression of mGHRF messenger RNA. These results suggest that mouse placenta produces and releases the mature mGHRF, which is indistinguishable by chromatographic criteria from that produced by the hypothalamus, and that signals through gp130 lead to the inhibition of mGHRF production and release in the mouse placenta.
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PMID:Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal transducer. 786 61

The mechanism by which the binding of growth hormone (GH) to its cell surface receptor elicits changes in gene transcription are largely unknown. The transcription factor Stat1/p91 has been shown to be activated by GH. Here we show that acute phase response factor or Stat3 f1p4an antigenically related protein), is also activated by GH. Stat3 has been implicated in the interleukin-6-dependent induction of acute phase response genes. GH promotes in 3T3-F442A fibroblasts the tyrosyl phosphorylation of a protein immunoprecipitated by antibodies to Stat3. This protein co-migrates with a tyrosyl phosphorylated protein from cells treated with leukemia inhibitory factor, a cytokine known to activate Stat3. Tyrosyl phosphorylated Stat3 is also observed in response to interferon-gamma. Stat3 is present in GH-inducible DNA-binding complexes that bind the sis-inducible element in the c-fos promoter and the acute phase response element in the alpha 2-macroglobulin promoter. The ability of GH to activate both Stat1 and Stat3 (i.e. increase their tyrosyl phosphorylation and ability to bind to DNA) suggests that gene regulation by GH involves multiple Stat proteins. Shared transcription factors among hormones and cytokines that activate JAK kinases provide an explanation for shared responses, while the ability of the different ligands to differentially recruit various Stat family members suggests mechanisms by which specificity in gene regulation could be achieved.
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PMID:Activation of acute phase response factor (APRF)/Stat3 transcription factor by growth hormone. 787 44

Tumor necrosis factor (TNF) is implicated in wasting syndromes and insulin resistance in chronic infection and obese-linked diabetes. TNF (10 ng/ml) inhibited adipocyte differentiation of 3T3-L1 cells, and in these TNF treated cells little insulin-stimulated glucose uptake was observed. Treatment of 3T3-L1 cells with troglitazone (1-10 microM) partially prevented this inhibitory effect of TNF on adipogenesis, and enhanced expression of C/EBP alpha and GLUT4, even in the presence of TNF. Troglitazone also prevented the inhibitory effects of interleukin-1, interleukin-6, and leukemia inhibitory factor, but not of transforming growth factor beta on adipocyte differentiation of 3T3-L1 cells. These effects might contribute to the antidiabetic effect of troglitazone in obese diabetic animals.
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PMID:Troglitazone prevents the inhibitory effects of inflammatory cytokines on insulin-induced adipocyte differentiation in 3T3-L1 cells. 795 51

When 15-deoxyspergualin (DSG) was administered into [BALB/c-->C3H/He] bone marrow (BM) chimeras from day 14 to day 25, increased platelet counts were observed from day 25 to day 33. Twofold increase of platelet counts was observed in DSG-treated BM chimeras compared with phosphate buffered saline (PBS)-treated BM chimeras. By using reverse transcriptase-polymerase chain reaction (RT-PCR), several cytokine mRNA expressions were analyzed in order to clarify which cytokines are involved in thrombopoiesis. So far, interleukin-6 (IL-6), leukemia inhibitory factor (LIF), stem cell factor (SCF), and IL-11 have been reported to have potent thrombopoietic activity in vivo. Although some other cytokines such as IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) possess the capacity of thrombopoiesis, megakaryocytopoiesis is more marked in these cytokines. IL-6 mRNA expression was increased in spleen cells from DSG-treated BM chimeras from day 25 to day 32 and in bone marrow cells from day 19 to day 28. LIF mRNA expression was not significantly increased compared with PBS control. Although SCF mRNA expression was increased, the kinetics of increased SCF mRNA expression did not fit the kinetics of increased platelet counts. Increased mRNA expression in other hematopoietic cytokines, such as IL-3, granulocyte-colony stimulating factor (G-CSF) and GM-CSF were also observed, thus suggesting that these cytokines may synergistically support thrombopoiesis in concert with IL-6. These results suggest that IL-6 and other hematopoietic cytokines might induce increased platelet counts, although the involvement of thrombopoietin (TPO) and IL-11 should be analyzed in the future.
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PMID:A novel immunosuppressant 15-deoxyspergualin and thrombopoiesis. 795 88

Human interleukin-11 (IL-11) is a cytokine with a broad spectrum of activity, similar to interleukin-6 (IL-6). However, its role in human disease is poorly understood, partly because of a lack of sensitive bioassays. A subclone (B9-11) obtained from the B9 hybridoma (which responds poorly to human IL-11) enabled us to develop a highly sensitive bioassay for human IL-11. B9-11 cells responded only to human IL-11 and IL-6 and not to other human cytokines using the same gp130 transducer chain (ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M) or to other human interleukins (interleukin-1 to interleukin-13), human hematopoietic cytokines (granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating factor, colony stimulating factor-1) and various other human cytokines (interferon-alpha, tumor necrosis factor-alpha, tumor necrosis factor-beta, fibroblast growth factor and nerve growth factor). In addition, these cytokines did not interfere with the IL-11 response of B9-11 cells. IL-11-induced proliferation of B9-11 cells was unaffected by anti-murine IL-6 receptor mAb but inhibited by anti-gp130 mAb. Half-maximal proliferation of B9-11 cells was obtained with 30 pg/ml of recombinant IL-11, a concentration 300-fold lower than IL-11 concentrations known to be active on human cells. Finally, culturing of B9-11 cells with an anti-IL-6 mAb enabled us to measure the natural IL-11 produced by various cell lines. Thus, B9-11 cells should be useful for studies of IL-11 involvement in various human diseases as well as for a better understanding of the mechanisms of action of this cytokine.
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PMID:A highly sensitive quantitative bioassay for human interleukin-11. 803 82

Interleukin-6 (IL-6) was found to be a pleiotropic cytokine which plays important roles not only in immune response but also in inflammation and hematopoiesis since the cDNA for IL-6 was originally cloned as a B cell differentiation factor (BCDF). IL-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor have similar effects with IL-6. This functional redundancy was well explained by the common signal transducer gp 130. Furthermore, recent studies have revealed the mechanisms to regulate the gene expression of IL-6 and to transduce the signal through IL-6 receptor system. On the basis of these results, elucidation of pathogenic significances of IL-6 and new therapeutic approaches in various diseases are now expected.
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PMID:[Interleukin-6]. 806 Jan 52


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