UNIPROT:P05231 - FACTA Search

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

We have investigated the effect of cytokines, including interleukin-6 (Il-6), interleukin-1 alpha (Il-1 alpha), and tumor necrosis factor-alpha (TNF-alpha), on the inducible expression of cytochrome P450s (CYP) CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. The ability of these cultures to mimic the acute phase response when stimulated with cytokines was evaluated using immunoblotting to measure the production of albumin, ferritin, fibrinogen, and ceruloplasmin. The cytokines exhibited specific patterns of action on the production of these proteins. Albumin was depressed by all the cytokines. In contrast to Il-6 and Il-1 alpha, TNF-alpha reduced the production of fibrinogen and ceruloplasmin but stimulated the production of ferritin. When cells were treated with the CYP inducer alone, large increases in the expression of CYP1A1 and CYP1A2 by beta-naphthoflavone and of CYP3A4 by rifampicin were observed at messenger RNA (mRNA) and protein levels, by ribonuclease protection and immunoblotting, respectively. When the cells were treated with the inducer plus cytokines, the induction of mRNA was greatly reduced. Again, specific patterns of action were revealed: Il-6 had the most potent effect on CYP3A4, whereas TNF-alpha was the most potent with CYP1A genes. In all cases, changes at the protein levels paralleled changes at the mRNA levels. In cells preinduced with beta-naphthoflavone or rifampicin, the decay with time of the levels of the CYP1A2 or CYP3A4 proteins, after the removal of the inducer, was not affected by cytokines. We conclude that cytokines strongly repress the inducibility of CYP1As and CYP3A4 genes at a transcriptional or a posttranscriptional level, but affect neither the rate of translation of CYP mRNAs nor the rate of degradation of the CYP proteins in these cultures.
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PMID:Differential effects of cytokines on the inducible expression of CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. 755 64

The regulation of acute phase protein production and the relationship of the acute phase protein response to tumour growth was examined in colorectal cancer patients (n = 9). Ibuprofen (1200 mg/d) was administered for 8-11 days. Following ibuprofen administration there were reductions in circulating concentrations of C-reactive protein (P = 0.01), interleukin-6 (P = 0.06), cortisol (P = 0.04) and also in the platelet count (P = 0.01). There was no significant change in albumin, insulin and carcinoembryonic antigen. These results indicate that ibuprofen administered over a prolonged period substantially reduces acute protein production via its effect on interleukin-6 and cortisol. It remains to be determined whether ibuprofen is useful in moderating tumour growth in colorectal cancer patients.
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PMID:Effect of extended ibuprofen administration on the acute phase protein response in colorectal cancer patients. 758

Interleukin-6 plays a key role in mediating acute-phase protein synthesis in hepatocytes. However, the mechanism of how interleukin-6 regulates aldolase B and albumin syntheses in hepatocytes is not completely understood. In this study, using primary cultured rat hepatocytes, we have shown that interleukin-6 down-regulates expressions of the aldolase B and albumin genes in a dose- and time-dependent manner. We examined whether the decrease in aldolase B and albumin mRNA expressions by interleukin-6 reflected transcriptional down-regulation or stability of the mRNA. Actinomycin D and cycloheximide did not affect the interleukin-6-mediated decrease in the expressions of both genes. These results suggest that the decreased expressions of both genes induced by interleukin-6 is controlled at the transcriptional level, and that it is due neither to increased degradation of mRNA nor to synthesis of new proteins. Protein kinases play a fundamental role in the intracellular signal transduction. To examine the interleukin-6 signal pathway(s) leading to the decrease of aldolase B and albumin mRNA expressions, we tested various kinds of protein kinase inhibitors in this system. Herbimycin A, an inhibitor of tyrosine kinase(s), prevented the decrease in the expression of aldolase B and albumin mRNAs by interleukin-6. H-7, an inhibitor of protein kinase C, prevented the decrease in the expression of albumin mRNA by interleukin-6, but did not induce recovery of that of aldolase B mRNA. These results suggest that a tyrosine kinase(s) or a herbimycin A-sensitive kinase(s) constitutes a common pathway for interleukin-6-mediated reduction of aldolase B and albumin mRNA expressions and that distinct pathways exist for the modes of expression of the two mRNAs.
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PMID:Interleukin-6 down-regulates expressions of the aldolase B and albumin genes through a pathway involving the activation of tyrosine kinase. 762 25

The control of metallothionein (MT) synthesis was investigated in freshly prepared rat hepatocytes in experiments of short-term duration. Viability and metabolic function were maintained in incubations of 6-h duration. MT synthesis was measurable in hepatocytes from fed rats at Zn concentrations down to 1 microM. Zn and dexamethasone induced concentration-dependent increases in the synthesis of MT with maximal increases above the 5-h control of 3.2- and 2.5-fold, respectively. Zn induction of MT was first measurable at 2 h and was inhibited by actinomycin C. Although initial (0 h) MT concentrations in hepatocytes from fasted rats were double those from fed rats, after 6-h incubation in the presence of 50 microM Zn, the fasted rat hepatocytes showed only half the MT concentrations of the fed rat hepatocytes. Glucagon and interleukin-6 (IL-6) were less effective inducers and increased MT synthesis by 28 and 17%, respectively. IL-6 (100 U/mL) was found to have an additive effect on MT synthesis above that of Zn alone (1-50 microM) or Zn plus dexamethasone (1 microM). A supernatant from LPS-stimulated macrophages increased MT synthesis by 40%. The basal MT synthesis was not increased by either tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 (IL-1). All incubations were carried out in the presence of RPMI 1640 medium with Hepes (20 mM), bicarbonate (24 mM), and fatty acid-free albumin (FAFA; 0.5% w/v). MT synthesis was also seen using Krebs bicarbonate buffer with glucose (10 mM), Hepes (20 mM), and FAFA (0.5% w/v), and although the level of MT synthesis was less than in RPMI, the increases in concentrations of MT at 5 h were 225, 139, 36 and 20% for Zn, dexamethasone, glucagon, and control, respectively. It is concluded that MT synthesis occurs in freshly prepared hepatocytes and that these cells are responsive to some of the established inducers of MT. This system enables the study of MT synthesis in individual rats in various metabolic and pathological states.
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PMID:Metallothionein induction in freshly isolated rat hepatocytes. 768 80

HepG2 cells were cultured for 7 days in serum-free medium in the presence of interleukin-6 (IL-6), retinoic acid (RA) or dexamethasone (DX), and some plasma proteins secreted to the media were determined by electroimmunoassay whereas the contents of specific mRNAs in the cells was evaluated by Northern blot hybridization. Interleukin-6 maximally stimulated synthesis of alpha-1-antichymotrypsin between days 1 and 3 whereas the response of fibrinogen was delayed to days 3 to 7. Retinoic acid increased the effect of IL-6 on alpha-1-antichymotrypsin (ACT) and fibrinogen (FBG) on the level of both proteins and mRNAs. Synthesis of albumin was slightly inhibited by IL-6 and RA, and synthesis of transferrin was increased by RA but not by IL-6. Dexamethasone had small enhancing effect on the action of IL-6. These results suggest that long-term HepG2 cultures may provide an experimental model for liver acute phase response during chronic inflammation.
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PMID:Long-term culture of HepG2 hepatoma cells as a model for liver acute phase response during chronic inflammation. Effects of interleukin-6, dexamethasone and retinoic acid. 769 40

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

Cytokines are widely involved in physiologic as well as immunoinflammatory and fibrosing processes of the lung. The aim of this work was to study, by bronchoalveolar lavage, two groups of human interstitial lung diseases (ILD) with fibrosing propensity (ie, idiopathic pulmonary fibrosis [IPF], n = 10; and coal worker's pneumoconiosis [CWP], n = 15). Patients were compared with nonsmoker control subjects (n = 20). Cellularity, proteins, and phospholipids were determined in the alveolar fluids. In addition, two cytokines (interleukin-6 [IL-6] and interferon-gamma [IFN-gamma]), which are presumed to possess respective antifibrotic and profibrotic activities, were measured in the respiratory tract. Compared with control subjects, IPF and simple CWP showed alveolar hypercellularity (p < 0.05) and relative lymphocytosis (p < 0.05). Both exhibited increased alveolar permeability (ie, increased albumin/urea ratio, p < 0.05), with enhanced IL-6 and decreased IFN-gamma in the alveolar spaces (p < 0.05). On the other hand, IPF displayed an associated polymorphonuclear alveolitis, enhanced alveolar epithelial lining fluid (AELF) volume and low surfactant phospholipid levels (p < 0.05 vs control), whereas simple CWP shared an exclusive lymphocytosis, normal AELF volume, and a surfactant lipid overflow (p < 0.05 vs control). Relationships among all of these parameters were found only between alveolar cellularity, neutrophils and IL-6 levels in the AELF of IPF (respectively, r = 0.85, p = 0.0009, and r = 0.89, p = 0.0006). In summary, common alterations of cellular and cytokine turnover were observed in IPF and simple CWP and may reflect activity of the antifibrotic fight in these diseased lungs. Surfactant phospholipid levels are likely to represent a specific disturbance among IPF and CWP, but no clear relationship with respect to the other parameters could be established for explaining the difference in time course outcome.
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PMID:Interleukin-6, interferon-gamma, and phospholipid levels in the alveolar lining fluid of human lungs. Profiles in coal worker's pneumoconiosis and idiopathic pulmonary fibrosis. 777 11

The relationship between urine interleukin-6 (IL-6) and interleukin-8 (IL-8)/creatinine quotients and 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy, performed within 10 days of acute first-time pyelonephritis and after 1 year, was studied in 41 children. The urine IL-6 and IL-8/creatinine quotients were also related to the urine N-acetyl-beta-D-glucosaminidase (NAG) and albumin/creatinine quotients. Presence of DMSA uptake defects, reflecting local inflammation, in children in the acute phase of pyelonephritis, were associated with elevated urine IL-6/creatinine quotients (median 27 pg/mumol); in children without DMSA changes there was no increase in quotients (median non-detectable) (P < 0.05). Persistent DMSA changes at the 1-year follow-up, probably reflecting renal scarring, were only seen in children with increased urine IL-6/creatinine quotients in the acute phase (P < 0.01). No correlation was found between urine IL-8 and DMSA uptake defects. Vesicoureteral reflux (VUR) at 6-8 weeks did not correlate with the urine cytokine levels in the acute phase. The urine excretion of NAG and albumin, reflecting renal dysfunction, was associated with values of both urine IL-6 and IL-8/creatinine quotients, but not with DMSA defects or VUR. Thus, the initial urine IL-6/creatinine quotients might be used as an indicator of risk for persistent renal damage in acute pyelonephritis.
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PMID:Urine interleukin-6 and interleukin-8 in children with acute pyelonephritis, in relation to DMSA scintigraphy in the acute phase and at 1-year follow-up. 788 89

The concentration of interleukin-6 (IL-6) was measured in the perfusion fluid from investigated rectal and sigmoid segments in patients with ulcerative colitis (UC). The colorectal release of this substance from segments with active inflammation was greatly increased compared with that found in healthy controls and correlated to the mucosal damage defined by plasma protein leakage and endoscopic findings. The perfusate/serum ratio of IL-6 was significantly higher than the corresponding ratio of albumin, indicating that the increased amount of IL-6 detected in the perfusion fluid was synthesized in the inflamed colorectal mucosa. A strong correlation between the concentrations of IL-6 and of tumor necrosis factor-alpha in perfusion fluid suggests that macrophages/monocytes are cells of importance in the stimulated local synthesis of IL-6. The calculated total colorectal release of IL-6 was significantly correlated to the serum concentrations of C-reactive protein and alpha 1-antitrypsin, demonstrating that the acute phase response in patients with UC reflects the amount of locally produced IL-6.
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PMID:Enhanced intestinal synthesis of interleukin-6 is related to the disease severity and activity in ulcerative colitis. 811 97

Plasma lysozyme levels are elevated in several different pathological conditions. In our study we show that well differentiated human hepatoma cells Hep3B and HepG2 are active synthesis sites of lysozyme and that this synthesis can be modulated by acute phase mediators. The production and modulation of lysozyme synthesis was studied by means of Northern-blot analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a specific bioassay after treatment of the cells with interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha. Hep3B and HepG2 cells constitutively synthesize high amounts of lysozyme. Lysozyme synthesis and secretion were found to be augmented by interleukin-1 beta and tumor necrosis factor-alpha in both cell lines. Interleukin-6 caused an increase in lysozyme production in Hep3B but a decrease in the HepG2 cells. As expected, the synthesis of albumin was decreased in both cell lines. Furthermore we demonstrated that HepG2 and Hep3B cells produce a biologically active form of the enzyme as measured by a specific bioassay. The results demonstrate that lysozyme is constitutively synthesized by Hep3B and HepG2 hepatoma cell lines and that lysozyme synthesis is modulated by acute-phase mediators. Well differentiated human hepatoma cells may respond differently to different cytokines.
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PMID:Human hepatoma cells synthesize and secrete lysozyme: modulation by cytokines. 817 40

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