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)

Immune defects, thyroid abnormalities, plasma zinc levels, and the presence of gastrointestinal disease were investigated in 43 children with Down's syndrome (DS). Peripheral T lymphocytes with the phenotype of helper cells or cluster of differentiation 4 (CD4) were decreased. Circulating activated T cells (CD3/HLA-DR-positive cells) and large granular lymphocytes (CD16/CD56 positive cells) were increased. Plasma levels of interleukin-6 were higher in DS children than in controls. Serum levels of thyroid-stimulating hormone were increased in DS. Coeliac disease was over-represented in the group of DS children and many of these children also showed increased serum levels of immunoglobulin-G (IgG) specific for gliadin antigen. The increment of serum interleukin-6 was age-related and correlated with anti-gliadin IgG levels in DS. Plasma zinc levels were lower in DS children with coeliac disease and in those with anti-gliadin IgG than in DS without detectable anti-gliadin IgG. Dietary antigens may represent a continuous stimulus for the immune system in this syndrome and interfere with normal immune responses. Altered intestinal absorption of nutrients may in turn affect endocrine functions, brain development, and cognitive performances.
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PMID:Immune-endocrine status and coeliac disease in children with Down's syndrome: relationships with zinc and cognitive efficiency. 1147 Mar 33

We previously reported that prostaglandin F2alpha (PGF2alpha) induces phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D through heterotrimeric GTP-binding protein, resulting in the activation of protein kinase C (PKC) in osteoblast-like MC3T3-E1 cells and that PGF2alpha stimulates the synthesis of interleukin-6 (IL-6) via PKC-dependent p44/p42 mitogen-activated protein (MAP) kinase activation. In the present study, we investigated whether zinc affects the PGF2alpha-induced IL-6 synthesis in these cells. Zinc complex of l-carnosine (l-CAZ) dose-dependently suppressed the PGF2alpha-stimulated IL-6 synthesis. In addition, zinc alone reduced the IL-6 synthesis. L-CAZ suppressed the PGF2alpha-induced p44/p42 MAP kinase phosphorylation. However, the p44/p42 MAP kinase phosphorylation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a direct activator of PKC, or NaF, a direct activator of GTP-binding protein, was not affected by l-CAZ. l-CAZ reduced the PGF2alpha-stimulated formation of inositol phosphates and choline. However, l-CAZ did not affect the formation of inositol phosphates or choline induced by NaF. These results strongly suggest that zinc reduces PGF2alpha-induced IL-6 synthesis via suppression of phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D in osteoblasts.
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PMID:Zinc suppresses IL-6 synthesis by prostaglandin F2alpha in osteoblasts: inhibition of phospholipase C and phospholipase D. 1196 2

The aim of this study was to examine solvent-associated effects on blood cytokine levels, antioxidant enzyme activities, and malondialdehyde (MDA) concentration in house painters. Trace element (Cu and Zn) and nitrite and nitrate levels as well as protein concentrations in erythrocytes and serum were determined. Thirty male house painters and 30 male clerical workers were included in the study. There were 13 smokers and 17 nonsmokers in each group. Hemoglobin concentrations were significantly lower in house-painter blood compared to controls. House painters had significantly higher concentrations of erythrocyte protein (excluding hemoglobin), whereas no significant difference was observed between serum protein levels. Proinflammatory cytokine levels, such as tumor necrosis factor-alpha and interleukin-8, were significantly increased in house painters' sera. Interleukin-6 was below the detection limit of the assay in both groups. Interleukin-1beta and cytokine receptor interleukin 2R concentrations were not significantly affected. Furthermore, a three- to fourfold increase in nitrite and nitrate concentrations was found in house painters' sera. Serum superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities were significantly lower in house painters compared to controls. Malondialdehyde (MDA) concentration, a measure of lipid peroxidation, was found to be significantly elevated. In house painters, erythrocyte carbonic anhydrase and catalase activities were elevated approximately 11- fold and 2-fold, respectively. Zinc levels were significantly decreased in house painters' sera. Smoking was not found to be a major confounder for the association between solvent exposure and blood parameters.
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PMID:Effects of long-term solvent exposure on blood cytokine levels and antioxidant enzyme activities in house painters. 1216 7

Concentrations of the calcium-binding proteins of the S100 family, myeloid-related proteins 8 and MRP 14 (MRP8/14), are elevated in chronic infections, yet the role of these proteins is not clearly defined. Using commercial and developed enzyme immunoassays, we assayed for MRP8/14 in sterile-filtered abscess fluid from tissue-cage-implanted rats and rabbits. Staphylococcus aureus abscesses were created 6 weeks after the intraperitoneal implantation of tissue cages. Leukocytes, bacteria, and non-protein-bound calcium and zinc were measured in the infection exudate at day 3 or 5 of infection and after 8 days of treatment with antimicrobials beta-lactams (18 rabbits, 35 rats) and fluoroquinolone-rifampin (6 rabbits). Half of the infected rats were depleted of neutrophils; these rats exhibited significantly lower MRP 8/14 concentrations on all days sampled, regardless of the level of infection. The level of abscess MRP 8/14 is high early in the course of infection but decreases with effective antimicrobial treatment by as much as 100-fold. Thirty-day-old abscesses with log 6 bacterial counts and low neutrophil counts showed low concentrations of MRP 8/14 in these models. In abscess fluid, interleukin-6, as a representative marker of inflammation, correlated with MRP8/14, whereas ionized calcium and zinc did not. Our data suggest that infection and inflammation are not equal stimuli for MRP 8/14. The neutrophil appears to be the main source of MRP8/14 in this model.
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PMID:Calcium-binding proteins MRP 8 and 14 in a Staphylococcus aureus infection model: role of therapy, inflammation, and infection persistence. 1257 47

Biomarkers of infection were screened for their possible role as evaluators of antibiotic treatment in an aerosol infection model of porcine pneumonia caused by Actinobacillus pleuropneumoniae (Ap). Following infection of 12 pigs, clinical signs of pneumonia developed within 20 h, whereafter the animals received a single dose of either danofloxacin (2.5mg/kg) or tiamulin (10 mg/kg). To test the discriminative properties of the biomarkers, the dosage regimens were designed with an expected difference in therapeutic efficacy in favour of danofloxacin. Accordingly, the danofloxacin-treated pigs recovered clinically within 24h after treatment, whereas tiamulin-treated animals remained clinically ill until the end of the study, 48 h after treatment. A similar picture was seen for the biomarkers of infection. During the infection period, plasma C-reactive protein (CRP), interleukin-6 and haptoglobin increased, whereas plasma zinc, ascorbic acid and alpha-tocopherol decreased. In the danofloxacin-treated animals, CRP, interleukin-6, zinc, ascorbic acid and alpha-tocopherol reverted significantly towards normalisation within 24h of treatment. In contrast, signs of normalisation were absent (CRP, zinc and ascorbic acid) or less marked (interleukin-6 and alpha-tocopherol) in the tiamulin-treated animals. Plasma haptoglobin remained elevated throughout the study in both groups. This indicates that CRP, zinc, ascorbic acid and to a lesser extent interleukin-6 and alpha-tocopherol might be used to evaluate antibiotic treatment of acute Ap-infection in pigs. The present model provides a valuable tool in the evaluation of antibiotic treatments, offering the advantage of clinical and pathological examinations combined with the use of biochemical infection markers.
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PMID:Putative biomarkers for evaluating antibiotic treatment: an experimental model of porcine Actinobacillus pleuropneumoniae infection. 1272 45

The cepIR genes encode an N-acyl homoserine lactone (AHL)-dependent quorum-sensing system consisting of an AHL synthase that directs the synthesis of N-octanoyl-L-homoserine lactone (ohl) and n-hexanoyl-L-homoserine lactone and a transcriptional regulator. The virulence of cepIR mutants was examined in two animal models. Rats were infected with agar beads containing Burkholderia cenocepacia K56-2, K56-I2 (cepI : : Tp(r)) or K56-R2 (cepR : : Tn5-OT182). At 10 days post-infection, the extent of lung histopathological changes was significantly lower in lungs infected with K56-I2 or K56-R2 compared to the parent strain. Intranasal infections were performed in Cftr((-/-)) mice and their wild-type siblings. K56-2 was more virulent in both groups of mice. K56-I2 was the least virulent strain and was not invasive in the Cftr((-/-)) mice. OHL was readily detected in lung homogenates from Cftr((-/-)) mice infected with K56-2 but was only detected at levels slightly above background in a few mice infected with K56-I2. Lung homogenates from mice infected with K56-2 had significantly higher levels of the inflammatory mediators murine macrophage inflammatory protein-2, KC/N51, interleukin-1beta and interleukin-6 than those from K56-I2-infected animals. These studies indicate that a functional CepIR quorum-sensing system contributes to the severity of B. cenocepacia infections. A zinc metalloprotease gene (zmpA) was shown to be regulated by CepR and may be one of the factors that accounts for the difference in virulence between the cepI mutant and the parent strain.
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PMID:The CepIR quorum-sensing system contributes to the virulence of Burkholderia cenocepacia respiratory infections. 1466 96

Metallothionein (MT)-III isoform is a brain metal-binding protein that, like the MT-I + II isoform, binds zinc with high affinity. In the young-adult age, MT-III isoform increases during transient stress while MT-I + II isoform decreases, suggesting compensatory phenomena between the two isoforms and a protective role of MT-III against oxidative damage. This role may be questioned during ageing, because the stress-like condition is chronic in ageing due to high persistent levels of interleukin-6. In the present study, high expression of MT-III and MT-I + II genes (examined by RT-PCR and in situ hybridisation) was found in the hippocampus of old rats. These results indicate that a large amount of free zinc ions can be sequestered by MT isoforms, leading to impaired zinc-dependent functions in the ageing brain. In addition, zinc (tested with the Timm's method) was found to be low in mossy fibres from the old hippocampus. As this method tests bound and unbound zinc, we also investigated free zinc ion bioavailability based on the ratio active thymulin/total thymulin. We found that zinc ion bioavailability was low in old rats, together with increased interleukin-6 mRNA, high expression of both MT isoforms and reduced number of synapses whose function is zinc-dependent, in the old hippocampus. The results indicate that concomitant increments of both MT isoforms may provoke detrimental synergistic effects leading to reduced free zinc ion bioavailability for synapses. As a consequence, compensatory phenomena between MT isoforms may not occur in the old hippocampus due to chronic stress-like condition elicited by high persistent levels of interleukin-6.
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PMID:Metallothionein isoforms (I+II and III) and interleukin-6 in the hippocampus of old rats: may their concomitant increments lead to neurodegeneration? 1513 Jul 2

A cadmium-binding protein with biochemical features of a metallothionein (MT) has been isolated and purified to homogeneity from the ciliate Tetrahymena thermophila. N-terminal sequencing revealed the posttranslational cleavage of the first two amino acids and, in general, a high degree of identity with known MTs from other ciliates. Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) analysis of the apothionein revealed a molecular mass (16,763 Da) higher to those of mammals and of other protozoa. Finally, quantitative real-time PCR has been used to investigate the susceptibility of this ciliate MT to gene activation in response to heavy metals and to other stressors. Our data indicate that while zinc is not effective at all and cadmium is the best inducer, other stress factors, such as mercury, copper, heat and hydrogen peroxide, also activated gene transcription. As in vertebrate cells, interleukin-6 (IL-6) that stimulates ciliate growth, was able to enhance MT gene synthesis. This complex of data seems to indicate a general role of this protein in stress response.
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PMID:Biochemical characterization and quantitative gene expression analysis of the multi-stress inducible metallothionein from Tetrahymena thermophila. 1530 93

Synthesis of metallothionein (MT) is induced by interferon-alpha (IFN-alpha) in vitro and in vivo. In addition, IFN-alpha promotes redistribution of zinc (Zn) from the plasma to the liver in mice. However, it is not clear if IFN-alpha induces hepatic MT synthesis directly or indirectly via liberation of other cytokines. In order to address this issue, we determined hepatic MT levels, Zn concentration in plasma, liver, and urine, and plasma levels interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFalpha) in rats following intramuscular injection of human IFN-alpha (1.5 x 10(6) UI/m(2)). Animals were housed in metabolic cages and sacrificed at various times after IFN-alpha administration. Zn concentrations in serum, urine, and hepatic tissue were determined by atomic absorption spectrophotometry. MT protein was measured using the MT silver saturation method and expression of MT-1 and MT-2 mRNA was measured by RT-PCR. Plasma levels of rat IL-1, IL-6, and TNFalpha were determined using an ELISA method. Hepatic MT levels began to increase at 2 h following IFN-alpha administration and reached maximum levels at 12 h post-treatment. Induction of MT gene expression was confirmed by increases in MT-1 and MT-2 mRNA levels 6, 12, and 18 h after IFN-alpha administration. IFN-alpha treatment also resulted in biphasic increases in hepatic Zn, with levels peaking at 2 h, the time-point when MT levels are first increased, and again at 18 h. Concurrently, there were decreases in serum Zn levels at these time points, suggesting IFN-alpha induced movement of Zn from the blood to hepatic tissue. The decrease in serum Zn was not due to increased excretion since urinary Zn levels were unaffected following IFN-alpha treatment. IFN-alpha administration had no effect on plasma IL-1, IL-6, and TNFalpha levels. These results show that IFN-alpha promotes the increase of hepatic MT levels and plasma/liver redistribution directly, without IL-1, IL-6, or TNFalpha participation.
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PMID:Interferon alpha induction of metallothionein in rat liver is not linked to interleukin-1, interleukin-6, or tumor necrosis factor alpha. 1600 9

Transcription regulators STAT1 and STAT2 are key components of the interferon signaling system leading to innate antiviral immunity. The related STAT3 protein is a regulator of interleukin-6-type cytokine signals and can contribute to both cell growth and death important for cancer gene regulation and tumor survival. These three STAT proteins are targeted for proteasome-mediated degradation by RNA viruses in the Rubulavirus genus of the Paramyxoviridae. A single viral protein, the V protein, assembles STAT-specific ubiquitin ligase complexes from cellular components. Simian virus 5 (SV5) targets STAT1, human parainfluenza virus 2 targets STAT2, and mumps virus targets both STAT1 and STAT3. Analysis of the V-dependent degradation complex (VDC) composition and assembly revealed several features contributing to targeting specificity. SV5 and mumps V proteins require STAT2 to recruit the STAT1 target, yet mumps V protein binds STAT3 independent of STAT1 and STAT2. All Rubulavirus V proteins tested require cellular DDB1 to target STATs for degradation but differ in the use of Roc1, which is essential for mumps V STAT3 targeting. Protein interaction analysis reveals that paramyxovirus V proteins can homo- and heterooligomerize and that the conserved cysteine-rich zinc-binding C-terminal domain is necessary and sufficient for oligomerization. Purified SV5 V protein spontaneously assembles into spherical macromolecular particles, and similar particles constitute SV5 and mumps VDC preparations.
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PMID:Composition and assembly of STAT-targeting ubiquitin ligase complexes: paramyxovirus V protein carboxyl terminus is an oligomerization domain. 1605 11

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