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)

Renal cell carcinoma cells produced the substance(s) which killed them (suicide factor(s)) after co-culture with mumps virus. The suicide factor(s) were heat-sensitive and were degraded with trypsin. Furthermore, actinomycin D inhibited the production of the substance(s) by cancer cells. Considering these facts, the substance(s) were thought to be protein(s) derived from de novo synthesis in cancer cells. It was demonstrated that renal cell carcinoma cells proliferated with the autocrine loop of interleukin-6 (IL-6). Mumps virus almost completely inhibited the IL-6 production in several hours. Because of these two facts, the suicide process might be initiated in renal cell carcinoma cells after encountering mumps virus, i.e. inhibition of the autocrine growth loop of IL-6 followed by the induction of an autocrine killing loop of unknown substance(s).
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PMID:Suicide process of renal cell carcinoma cells encountering mumps virus. 199 9

Although fibroblasts are important in providing a structural framework for most tissues, they also appear to be active participants in the inflammatory process via the production of specific mediators. The production of inflammatory mediators by fibroblasts is especially important in relation to their strategic location within connective tissue as they may act as a cellular communication bridge between the interstitium and vasculature. In this paper, we demonstrate that fibroblasts may participate in these inflammatory reactions by the production of a neutrophil chemotactic factor (NCF) with characteristics similar to a recently isolated and cloned monocyte-derived NCF. Either tumor necrosis factor-alpha-, interleukin-1 alpha-, or interleukin-1 beta-stimulated fibroblasts showed both a time- and dose-dependent increase in steady-state levels of NCF mRNA and secretion of chemotactic activity. In contrast, lipopolysaccharide and interleukin-6 failed to induce fibroblast-derived NCF. The expression of fibroblast-derived NCF mRNA was first detectable by 30 min poststimulation, whereas chemotactic activity was significantly observed 3-4 h postchallenge. Heat-inactivated monokine (100 degrees C) failed to induce NCF mRNA expression, suggesting that only the active proteins are capable of inducing NCF. Gel filtration analysis using high pressure liquid chromatography indicated peak chemotactic activity with an approximate molecular mass of 8000 daltons. This peak of NCF activity was found to be relatively stable to both heat and trypsin inactivation. Specificity of the fibroblast-derived neutrophil chemotactic activity was demonstrated with inhibition of chemotaxis by the addition of neutralizing antibody directed against recombinant human neutrophil chemotactic factor. These data provide evidence that monokine-treated fibroblasts can synthesize a potent chemotactic agent with molecular and physicochemical characteristics similar to monocyte-derived NCF and that this factor may contribute to neutrophil-mediated disease processes.
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PMID:Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts. 265 89

We generated > 10(7) mast cells by culturing 10(7) cord blood mononuclear cells for > 10 weeks in the presence of Steel factor, interleukin-6 and prostaglandin E2. 99% of the cultured cells had tryptase-positive granules, while 18% had chymase-positive granules. Cultured mast cells contained 3.6 micrograms histamine and 3.5 micrograms tryptase per 10(6) cells. Cells sensitized with 1 microgram/ml human IgE released 58.5% histamine and 1.55 ng tumor necrosis factor (TNF)-alpha per 10(6) cells when challenged with 1 microgram/ml antihuman IgE, whereas the control cells spontaneously released 3.7% histamine and 0.18 ng TNF-alpha. Analysis for surface antigens revealed that cultured mast cells expressed the following CD molecules: 9, 13, 14, 29, 33, 38, 43, 44, 45RA, 45RB, 46, 47, 48, 49d, 50, 51, 53, 54, 55, 58, 59, 60, 61 and 117 (c-Kit). Taken together, these cultured cells seem to be functionally mature mast cells.
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PMID:Characterization of cord-blood-derived human mast cells cultured in the presence of Steel factor and interleukin-6. 754 4

In severe acute pancreatitis (SAP), the mechanisms leading to adult respiratory distress syndrome (ARDS) are usually attributed to the release of active enzymes and vasoactive substances from the pancreas. Thoracic duct drainage has been proposed as a means of removing the portion of these substances that drain through retroperitoneal lymphatics before they reach the systemic circulation. This technique was used in six patients with ARDS complicating SAP. The levels of proinflammatory cytokines (tumor necrosis factor-alpha [TNF alpha], interleukin-1 [IL-1], and interleukin-6 [IL-6]), neutrophil enzymes (myeloperoxidase and lactoferrin), and pancreatic enzymes (amylase, lipase and trypsin) were measured in plasma and lymph in the first 24 h of ARDS and then on Day 2, Day 4, and at the end of the drainage (Day 8). High plasma concentrations of these products were measured. A moderate lymph-to-plasma gradient was observed for IL-6, lipase, and trypsin, while similar levels in plasma and lymph were recorded for the other substances. Plasma levels of pancreatic enzymes were weakly correlated with the lung injury score and lymph level of cytokines. These results suggest that in patients with ARDS due to SAP, cytokines as well as pancreatic enzymes could contribute to the development of the lung injury, and that lymphatics are potential vectors of these mediators.
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PMID:Lymphatic release of cytokines during acute lung injury complicating severe pancreatitis. 758 88

To infer possible mechanisms of acute airway inflammation and mucus hypersecretion in acute severe asthma, we performed cellular and biochemical analysis on sputum from 18 adults with acute severe asthma and compared the results with results of analysis of sputum from 12 adults with cystic fibrosis (CF). We found that in subjects with asthma neutrophils made up more than 75% of sputum cells in 10 samples whereas eosinophils made up more than 75% of cells in only three samples. Fifty percent of the subjects with asthma reported that their asthma exacerbation was precipitated by a respiratory tract infection, and these subjects had a significantly higher percentage of neutrophils in their sputum (85% +/- 6% vs 57% +/- 12%, p = 0.05). In the CF samples neutrophils made up more than 95% and eosinophils less than 1% of cells in all samples analyzed. Analysis of fluid phase chemicals in asthmatic and CF sputum samples showed that despite overall lower mean values of neutrophil elastase (27 +/- 11 micrograms/ml vs 466 +/- 121 micrograms/ml, p = 0.0001) and interleukin-8 (IL-8) (55 +/- 15 ng/ml vs 186 +/- 24 ng/ml, p = 0.0001), some of the asthmatic samples had values for these variables that overlapped those in the CF samples. In addition, the asthmatic samples were distinguished by the presence of higher tryptase (10 +/- 7 U/L vs 0.9 +/- 0.9 U/L, p = 0.0001) and interleukin-6 (1166 +/- 447 ng/ml vs 186 +/- 24 ng/ml; p = 0.0001) levels and by a higher ratio of albumin to mucin-like glycoprotein (0.8 +/- 0.5 vs 0.1 +/- 0.002, p = 0.02). DNA levels were lower in the asthmatic samples (0.5 +/- 0.3 mg/ml vs 3.5 +/- 1.2 mg/ml, p = 0.05). We conclude that neutrophils predominate more frequently than eosinophils as the major inflammatory cell in sputum from patients with asthma in acute exacerbation. We speculate that this may be because respiratory tract infections are a frequent precipitant of acute asthma. In addition, the high IL-8 levels and free neutrophil elastase activity observed in asthmatic sputum suggests that IL-8 may mediate airway neutrophilia in acute asthma and that neutrophil elastase may mediate mucin glycoprotein hypersecretion in acute asthma, as has been proposed for the mucin hypersecretion in CF.
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PMID:Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. 772 65

It has previously been reported that two kinds of human gastric adenocarcinoma cell lines (STKM-1 and MKN28) secrete a trypsin-like enzyme. In this study, four molecular forms of the enzyme (26, 25, 24 and 23 kDa on non-reducing SDS/PAGE) were purified from the serum-free conditioned medium of STKM-1 cells. Analysis of N-terminal amino acid sequences showed that the 26 kDa protein was a two-chain form of trypsinogen 1 which had been produced by proteolytic cleavage of the Arg107-Val108 bond of trypsinogen 1, and the 24 kDa protein was the one-chain form of trypsinogen 1. The 25 and 23 kDa proteins were the activated forms of the two-chain and one-chain trypsinogen 1 respectively. Isoelectric focusing gave pI values of 6.3 and 6.6 for the 26 kDa two-chain form and the 24 kDa one-chain form of trypsinogen 1 respectively. Comparison of the proteolytic activities indicated that the one-chain trypsin 1 had amidolytic activity about four times higher than that of the two-chain enzyme.
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PMID:Identification of one- and two-chain forms of trypsinogen 1 produced by a human gastric adenocarcinoma cell line. 794 38

The supernatant of a cell line of squamous cell carcinoma of the head and neck (SCCHN), PCI-50, was previously shown to induce activation, promote proliferation and increase antitumor cytotoxicity of freshly purified human natural killer (NK) cells and CD4+ T lymphocytes [Arch Otolaryngol Head Neck Surg (1994) in press]. This supernatant was found also to promote the growth of a variety of hematopoietic cell lines, including Jurkat, THP-1, K562, NK-92 or Epstein-Barr-virus-transformed B cell lines. The Jurkat cell line was selected as a reporter cell in an 18-h proliferation assay established to measure the growth-promoting activity of PCI-50 supernatant. The presence of soluble tumor-derived factors able to induce proliferation of Jurkat cells was demonstrated in the supernatant produced by several other SCCHN cell lines but not in that produced by a gastric cancer cell line (HR) or renal cell carcinoma line (5117G8). The growth-promoting PCI-50 supernatant was shown to contain 28 +/- 0.5 pg/ml interleukin-6 (IL-6) in vitro but was negative for interferon gamma, IL-1, IL-2, IL-4, tumor necrosis factor alpha, granulocyte/macrophage-colony-stimulating factor and IL-12. The addition of any of these recombinant cytokines to Jurkat cell cultures did not significantly promote growth, while PCI-50 supernatant was consistently growth-stimulatory. This supernatant neither enhanced intracellular Ca2+ concentration in Jurkat cells nor induced up-regulation of activation antigens on the cell surface, although it supported growth of Jurkat cells in the absence of IL-2. The growth-promoting activity in the PCI-50 supernatant was acid-labile at pH 2 for 4 h, heat-resistant at 96 degrees C for 1 h and sensitive to treatments with trypsin and pepsin. Preincubation of the PCI-50 producer cells with tunicamycin or cyclohexamide reduced the level of growth-promoting activity in the supernatant. A partial purification of this activity was achieved using Amicon filtration, chromatography on concanavalin-A-Sepharose and then a hydroxyapatite column and high-pressure liquid chromatography gel filtration. The partially purified glycoprotein had a molecular mass of 50-70 kDa, as determined by gel filtration.
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PMID:Proliferation of hematopoietic cell lines induced by a soluble factor derived from human squamous cell carcinomas of the head and neck. 800 Oct 29

A human myeloma cell line, PCM6, was newly established from peripheral blood of a patient with advanced IgG myeloma by addition of recombinant interleukin-6 (IL-6) in culture. PCM6 cells had a morphology typical of mature plasma cells. Cytogenetic and surface marker studies confirmed that PCM6 cells were identical to fresh myeloma cells. Coculture of PCM6 cells with normal bone marrow mononuclear cells resulted in increased colony size of bone marrow-derived fibroblastoid colony-forming cells (CFU-F). Conditioned medium of PCM6 (PCM6-CM) cells increased the CFU-F colony size in a dose-dependent manner. The activity was labile to trypsin treatment but was heat stable (60 degrees C, 30 minutes). Molecular weight of the activity was approximately 165 kd by Sephacryl S-300 gel filtration. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), and IL-1 beta were not detectable in the conditioned medium. These findings suggest that in some myeloma cases, bone marrow stroma may be affected by CFU-F growth-promoting activity.
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PMID:Establishment of a human myeloma cell line with growth-promoting activity for bone marrow-derived fibroblastoid colony-forming cells. 811 25

The basophilic leukaemia cell line KU812 can be induced to differentiate into basophil-like cells in vitro when exposed to supernatant from the Mo T-cell line. KU812 cells express affinity receptors for IgE, produce histamine and tryptase and have the capacity for IgE-mediated histamine release. In this study we have examined the cytokines, produced by the Mo cell line, which are responsible for the observed differentiation-inducing effect in the KU812 cell line. It was shown that interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) induced differentiation in the KU812 cells and that these cytokines were responsible for the differentiation-inducing effect of the Mo supernatant. Other cytokines tested, IL-1 beta, IL-2, IL-4, IL-5, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor (NGF) were without effect on the KU812 cells. KU812 was also shown to express receptors for both TNF-alpha and IL-6 after 3 days cultivation with conditioned media from the Mo T-cell line. Untreated cells showed no detectable levels of TNF-alpha or IL-6 receptors indicating induction of these receptors during differentiation. Spontaneous differentiation was shown to occur under serum-free conditions which may be the result of endogenous IL-6 production through an autocrine loop. The activity of TNF-alpha and IL-6 could be blocked by specific monoclonal antibodies (mAb) to the respective cytokine.
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PMID:TNF-alpha and IL-6 induce differentiation in the human basophilic leukaemia cell line KU812. 813 23

Nuclear factor-interleukin-6 (NF-IL6), a member of the CCAAT box/enhancer-binding protein (C/EBP) family, contains a basic domain-leucine zipper (bZIP) DNA binding motif. Controlled protease digestion was used to probe free and DNA-complexed NF-IL6 protein. Digestion with trypsin in the absence of DNA produced the leucine zipper domain (containing residues 303-345). In contrast, digestion of NF-IL6.DNA complexes produced a stable domain, spanning residues 266-345, termed the tryptic core domain (TCD). The NH2-terminal boundary of the TCD is longer than tryptic peptides reported from C/EBP alpha.DNA complexes. Digestion of NF-IL6 with endoprotease Asp-N produced a domain smaller than the TCD (NF-IL6 bZIP domains (NFBD) (272-345)), a domain identified either in the absence or the presence of DNA. Both recombinant peptides bind acute-phase response element DNA in a sequence-specific fashion. The equilibrium disassociation constant (Kd) for the TCD was 36 +/- 8 nM, whereas the Kd for NFBD (272-345) was 283 +/- 160 nM. Moreover, in comparison with the TCD, NFBD (272-345) formed unstable DNA complexes with a 15-fold faster off-rate. We conclude that the amino acids represented between 266 and 272 termed the complex stabilizing subdomain, influences DNA complex formation independent of DNA binding specificity, and may be one mechanism for heterogeneity of DNA interaction by C/EBP family members.
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PMID:Identification of a novel determinant for basic domain-leucine zipper DNA binding activity in the acute-phase inducible nuclear factor-interleukin-6 transcription factor. 814 15


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