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)

A novel hemopoietic CSF has been identified in the medium conditioned by lectin-stimulated human T cells. The cDNA clone encoding this factor, isolated by functional expression cloning in monkey cos-1 cells, proved to be identical with the cDNA encoding the cytokine B cell stimulatory factor-2/IFN-beta 2, a factor now known as IL-6. In the murine system, IL-6 indirectly supports the formation of several different types of hemopoietic colonies, including those derived from early blast cells, and directly supports the proliferation of granulocyte/macrophage progenitors. These results expand the range of known target cells of IL-6 to include hemopoietic progenitors in addition to B cells, T cells, and fibroblasts and provide further evidence that this cytokine plays an important role within a network of interacting cytokines that regulates many different biologic responses.
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PMID:Stimulation of murine hemopoietic colony formation by human IL-6. 325 92

Human hybridoma growth factor (HGF) has been purified to homogeneity and identified with the 26kDa protein, interferon-beta 2 (IFN-beta 2), B-cell stimulatory factor-2 (BSF-2) and hepatocyte stimulatory factor (HSF). This factor, renamed interleukin-6 (IL-6), can be induced in fibroblasts by IL-1, while other cytokines are less active or inactive as inducers. The possible use of this IL-6 induction as an alternative indirect assay system for IL-1 is considered. Also, the direct HGF activity as a test IL-6 has been compared with the other biological activities of IL-6. It was concluded that the HGF assay is the most sensitive, specific and convenient test for IL-6.
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PMID:Induction of hybridoma growth factor (HGF), identical to IL-6, in human fibroblasts by IL-1: use of HGF activity in specific and sensitive biological assays for IL-1 and IL-6. 326 77

Supernatants of mitogen-stimulated human leukocytes contain two biologically related cytokines, IL-1 and hybridoma growth factor (HGF). IL-1 beta is a potent inducer of HGF in fibroblasts but has little stimulating effect on monocytes that spontaneously produce HGF. Leukocyte-derived HGF and IL-1 were separated by the use of affinity chromatography on specific antibodies and discriminating assay systems for both cytokines. They had different Mr upon gel filtration and SDS-PAGE. In contrast to IL-1 beta, HGF showed heterogeneity on a cation-exchange column. IL-1 beta and HGF were purified to homogeneity by a sequence of four and five purification steps, respectively. Leukocyte-derived HGF was characterized by analysis of its NH2-terminal amino acid sequence. This revealed complete homology with fibroblast-derived HGF, 26-kDa protein, IFN-beta 2, and B cell stimulatory factor 2, molecules which have collectively been designated as IL-6. IL-1 beta exerted an antiviral and growth-promoting effect of fibroblasts, whereas HGF/IL-6 did not. Both IL-1 and IL-6 possessed lymphocyte-activating factor activity, which could be neutralized only by an anti-serum against the corresponding cytokine.
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PMID:Separation and comparison of two monokines with lymphocyte-activating factor activity: IL-1 beta and hybridoma growth factor (HGF). Identification of leukocyte-derived HGF as IL-6. 327 16

Human fibroblast cultures, when stimulated with interleukin-1 (IL-1) produce a growth factor for B-cell hybridoma and plasmocytoma cell lines. The availability of both a fast-growing and high-producer cell line (MG-63 osteosarcoma cells) and of a highly sensitive and specific assay system for this hybridoma growth factor (HGF) allowed us to obtain analytically pure preparations. Crude HGF from MG-63 cells was processed through a five-step concentration and purification schedule. Sequential adsorption to controlled pore glass (CPG) beads, antibody affinity chromatography and gel filtration resulted in a 10,000-fold purification to a specific activity of 10(9) units/mg HGF. Electrophoretically pure HGF was obtained after additional purification by cation-exchange chromatography and reversed-phase HPLC. The purification procedure revealed two distinct biologically active HGF components. The amino-terminal sequence of one of the two components was determined and found to correspond to that already predicted from cDNA clones of a protein alternatively called 26-kDa protein, interferon-beta 2 (IFN-beta 2) or B-cell stimulating factor-2 (BSF-2). The first two designations (26-kDa protein and IFN-beta 2) refer to a postulated fibroblast secretory protein with so far no unambiguously defined function; the latter designation (BSF-2) refers to a T-cell product possessing differentiation stimulatory effect on B-cell lines. The reported results firmly establish that the protein is secreted by fibroblasts and reveal that it possesses B-cell growth stimulatory activity. The new designation interleukin-6 (IL-6) is proposed to resolve prescribing nomenclature confusion.
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PMID:Purification and characterization of human fibroblast-derived hybridoma growth factor identical to T-cell-derived B-cell stimulatory factor-2 (interleukin-6). 349 18

Interferons (IFNs), as well as some interleukins, growth factors, and hormones, all induce tyrosine phosphorylation of STAT1 and additional transcription factors of similar sizes. These factors are activated to translocate to nucleus and bind to enhancers of consensus sequence TTnCnnnAA (gamma-IFN activated sequence-like enhancers). In mammary cells or hybridoma B9 cells, four distinct tyrosine-phosphorylated transcription complexes activated by interleukin-6 (IL-6) and IFN-beta were observed: pIRFA and complexes I, II, and III (of increasing electrophoretic mobility). The factors have unequal affinities for enhancers of different genes; they are activated with distinct kinetics and to different extents by IL-6 and IFNs. The pIRFA band isolated from IL-6-stimulated B9 hybridoma cells revealed three DNA-interacting components: two large subunits of 91 and 98 kDa, as well as a small component of 46 kDa not seen in other complexes analyzed. One of the large pIRFA subunits may be APRF/STAT3, since pIRFA reacted with anti-APRF antibodies as do complexes I and II. However, pIRFA did not react with antibodies to STAT1, indicating STAT1 is not the other large component of pIRFA. Complex II, which reacted to anti-acute phase response factor antibodies also reacted to anti-STAT1 antibodies, whereas complex III reacted only to anti-STAT1 and was the only complex resistant to N-ethylmaleimide. By its multimeric subunit structure and its cytokine and enhancer sequence specificities, the slowly migrating pIRFA band appears as a novel tyrosine-phosphorylated transcription complex acting on a subset of gamma-IFN activated sequence-like enhancers.
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PMID:Interleukin-6 signaling via four transcription factors binding palindromic enhancers of different genes. 752 3

The effects of interleukin-6 (IL-6) on interferon regulatory factor 1 (IRF-1) gene expression were studied in B-hybridoma B9 cells which are growth-stimulated by IL-6 and breast carcinoma T47D cells which are growth-inhibited. IL-6 induced the production of IRF-1 mRNA and protein in both cell types, but IRF-1 binding activity to its target DNA sequence was induced only in T47D cells. With B9 cells, there was no IRF-1 binding but instead strong constitutive binding of the IRF-2 repressor, indicating that binding of IRF-1 to DNA is an important regulatory step. The IRF-1 gene promoter element, palindromic IFN-response element (pIRE), was found to respond to IL-6 with high efficiency as compared with IFN-gamma or IFN-beta. On this palindromic TTC...GAA sequence, two protein complexes (pIRE-a and pIRE-b) were induced within minutes by IL-6. pIRE-b is similar to the main complex induced by IFN-gamma and contains the Stat91 protein. pIRE-a predominantly induced by IL-6 is a slowly migrating complex which does not contain Stat91 and has low affinity for IFN-gamma activated sequence (GAS)-type sequences. Comparison of the relative effects of IL-6 and IFN-gamma shows that pIRE enhancers are differently regulated than GAS elements. Distinct transcription complexes, forming in ratios dependent on the inducer, help explain how various cytokines sharing effects through Stat91 on related enhancers can produce specific patterns of gene expression. Activation of the pIRE-a factors defines a novel transcriptional activity of IL-6 in epithelial and lymphoid cells.
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PMID:Induction by interleukin-6 of interferon regulatory factor 1 (IRF-1) gene expression through the palindromic interferon response element pIRE and cell type-dependent control of IRF-1 binding to DNA. 816 91

Immunocytochemical staining of spinal cords from five autopsied patients with HTLV-I-associated myelopathy/tropical spastic paraparesis was performed using a panel of monoclonal or polyclonal antibodies reactive with interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-beta, IFN-gamma and transforming growth factor (TGF)-beta. In the spinal cords of patients with a shorter duration of illness, IL-1 beta, TNF-alpha, and IFN-gamma were expressed on perivascular infiltrating macrophages, astrocytes and microglia in active-chronic inflammatory lesions. In striking contrast, we rarely noted cytokine expression except for IFN-gamma in inactive-chronic lesions of patients with longer durations. In situ expression of these cytokines on microglia and astrocytes, in addition to infiltrating mononuclear cells, suggests that glial cells participate in the inflammatory process, especially in active lesions. In addition, the cytokine expression was gradually downregulated along with duration of illness.
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PMID:Cytokine expression in the spinal cord lesions in HTLV-I-associated myelopathy. 830 22

Lipopolysaccharide treatment of mouse macrophage-like J774 cells was found to result in the activation of three different nuclear proteins which specifically bind to oligonucleotide containing the NF-kappa B motif of the human immunodeficiency virus (HIV) gene. These are designated as NF-kappa B1, -kappa B2, and -kappa B3, according to their electrophoretic mobilities (fast, intermediate, and slow, respectively). Immunological and UV cross-linking studies showed that NF-kappa B1 consists of only p50 subunit, whereas both NF-kappa B2 and -kappa B3 contain NF-kappa B p65 subunit and c-Rel. In addition, NF-kappa B2 was also found to contain p50 subunit of NF-kappa B. The binding of three types of NF-kappa B proteins to HIV NF-kappa B motif was effectively inhibited by other NF-kappa B motifs, whose 3' half-site nucleotide sequences are T/A-T-T/C-CC (HIV, interleukin-6, interferon (INF)-beta, H2-Kb, I-E alpha d, and TNF-alpha 2 (nucleotide position -510)) and much less effectively by NF-kappa B motifs with 3' half-site sequences of TGCCC (TNF-alpha 3, nucleotide position -610), ATCTC (G-CSF), TATTC (Fc gamma R), or TCCTT (TNF-alpha 1, nucleotide position -850). Our data also suggested that NF-kappa B1 and -kappa B2 which contain p50 subunit of NF-kappa B bind with the higher preference for NF-kappa B motif of H2-Kb gene promoter than that of INF-beta, whereas NF-kappa B3 which does not contain p50 subunit appears to preferentially bind to NF-kappa B sites of IFN-beta.
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PMID:Influence of 3' half-site sequence of NF-kappa B motifs on the binding of lipopolysaccharide-activatable macrophage NF-kappa B proteins. 836 97

Type I interferons (IFNs-alpha and IFN-beta) bind to a common receptor to exert strong antiproliferative activity on a broad range of cell types, including interleukin-6 (IL-6)-dependent myeloma cells. In this study, we investigated the effect of IFN-beta pretreatment on IL-6-stimulated mitogenic signaling in the human myeloma cell line U266. IL-6 induced transient tyrosine phosphorylation of the IL-6-receptor signal-transducing subunit gp130, the gp130-associated protein tyrosine kinases Jak1,Jak2, and Tyk2, the phosphotyrosine phosphatase PTP1D/Syp, the adaptor protein Shc and the mitogen-activated protein kinase Erk2, and accumulation of GTP-bound p21ras. Prior treatment of U266 cells with IFN-beta downregulated IL-6-induced tyrosine phosphorylation of gp130, Jak2, PTP1D/Syp, Shc, and Erk2, and GTP-loading of p21ras. Further analysis indicated that treatment with IFN-beta disrupted IL-6-induced binding of PTP1D/Syp to gp130 and the adaptor protein Grb2; IFN-beta pretreatment also interfered with IL-6-induced interaction of Shc with Grb2 and a 145-kD tyrosine-phosphorylated protein. These results suggest a novel mechanism whereby type I IFNs interrupt IL-6-promoted mitogenesis of myeloma cells in part by preventing the formation of essential signaling complexes leading to p21ras activation.
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PMID:Interferon-beta interrupts interleukin-6-dependent signaling events in myeloma cells. 897

Human hydatidosis is a parasitic disease vectored by the larval stage cestode Echinoccocus granulosus. It constitutes a major health problem in North Africa. We investigated the production of circulating interferon (IFN), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in Algerian patients with liver, lung, or ocular hydatidosis. In all, 101 serum samples from these patients with analyzed. Immunoreactivity and cytokine activities were undetectable in sera from ocular hydatidosis patients. However, we observed the presence of IFN (a mixture of IFN-alpha, IFN-beta, and IFN-gamma, range 32-500 U/ml), TNF-alpha (range 32-100 U/ml), and IL-6 (range 32-500 U/ml) in all patients who had liver or lung cysts or both and displayed immunoreactivity against parasitic antigen (antigen 5). After surgical removal of the cysts, serum cytokine levels declined rapidly and were undetectable at 30 days. IFN and IL-6 activity was undetectable in sera from two liver hydatidosis patients who relapsed and did not display any immune response against parasitic antigen. These results suggest that in liver and lung hydatidosis, cytokine production contributes to the host defense mechanism against the extracellular parasite.
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PMID:Relationship among circulating interferon, tumor necrosis factor-alpha, and interleukin-6 and serologic reaction against parasitic antigen in human hydatidosis. 914 50


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