Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T4-binding globulin (TBG) shares a high degree of homology with two serpin antiproteases, alpha 1-antichymotrypsin (ACT) and alpha 1-antitrypsin (AT), whose synthesis is increased during the acute phase phenomenon, which accompanies trauma, infections, and neoplasms. Interleukin-6 (IL-6) is believed to be the main effector of the acute phase response. When evaluated in human hepatoblastoma-derived (Hep G2) cells exposed to different doses of the recombinant human cytokine for variable time intervals, IL-6 caused a dose- and time-dependent decrease in the secretion of [35S]methionine-labeled TBG, transthyretin (TTR), and albumin. The secretion of ACT and AT was increased. These changes were not due to alterations in the secretory process, since the kinetics of secretion of newly synthesized proteins were not modified. IL-6 did, however, cause a decrease in the steady state levels of mRNA for TTR, TBG, and albumin and an increase in ACT and AT mRNAs. In addition, nuclear run-off assay demonstrated a decrease in the transcription of TTR, TBG, and albumin genes and an increased transcription of the ACT gene. Quantitation of the results showed that changes in the secretion of proteins, in steady state mRNA levels, and in gene transcription were superimposable for each protein, indicating that IL-6 exerts its effect on thyroid hormone-binding proteins mostly at the transcriptional level and that TTR is the thyroid hormone-binding protein showing the most pronounced negative regulation by IL-6. The opposite effect of IL-6 on TBG and the antiproteases, despite their structural homology, underscores gene divergence among these proteins.
 ...
PMID:Effects of interleukin-6 on the expression of thyroid hormone-binding protein genes in cultured human hepatoblastoma-derived (Hep G2) cells. 132 58

beta 2-microglobulin (beta 2-M) was secreted in a dose- and time-dependent manner after interleukin-6 (IL-6) treatment of human hepatoblastoma (HuH-6) and hepatoma cells (HuH-7). Pancreatic secretory trypsin inhibitor, which is one of the acute phase proteins secreted in these cells, was also secreted dose- and time-dependently in HuH-6 cells and dose-dependently in HuH-7 cells. It is conceivable that IL-6 induces the production of beta 2-M as an acute phase protein in the liver.
 ...
PMID:Secretion of beta-2-microglobulin from human hepatoblastoma and hepatoma cells on stimulation with interleukin-6. 132 81

The asialoglycoprotein receptor (AGPR) is responsible for the catabolism of acute phase proteins. The effects of inflammation-related cytokines on the expression of AGPR were investigated in HepG2 cells derived from a human hepatoblastoma cell line. Binding studies, using a [125I]-labeled asialo-orosomucoid ligand, revealed that AGPR numbers on cell surfaces were increased by interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). In cells treated with IL-1, IL-6, or TNF, immunohistochemical staining with an anti-AGPR monoclonal antibody demonstrated augmented expression. Pulse labeling analysis, using [35S]-labeled methionine, showed newly synthesized AGPR in both the precursor and the mature forms. When IL-1, IL-6, and TNF were added to the culture medium, total synthesis of AGPR (sum of the mature and precursor forms) was increased. In addition, the relative proportion of the synthesized precursor form of AGPR was higher in cytokine-treated than in untreated cells, suggesting that these cytokines augment the synthesis of AGPR, particularly in the stage prior to glycosylation.
 ...
PMID:Regulation of asialoglycoprotein receptor synthesis by inflammation-related cytokines in HepG2 cells. 751 7

In the present study, the distal part of the 5'-flanking region of the rainbow trout metallothionein-A promoter was sequenced in order to identify cis-acting regulatory elements. Analysis of this sequence combined with that previously reported for the 5'-flanking region directly proximal to the start of transcription revealed several putative regulatory sequences. In total, six metal-responsive elements (MREs) were identified; these sequences were organised into two clusters, one containing two copies of MRE and located close to the predicted TATA box sequence, and a second consisting of four MREs and lying 500-700 bp upstream from the start of transcription. In addition, the 5'-flanking region contained sequences sharing high similarity with the activator protein 1 consensus sequence as well as one nuclear-factor-interleukin-6-responsive element. Functional analysis of the promoter was performed by introducing deletion mutants of the 5'-flanking region into the vector pGL-2, directly upstream from the luciferase reporter gene. Both MRE clusters were needed for maximal metal inducibility in both rainbow trout hepatoma (RTH-149) and human hepatoblastoma (Hep G2) cell lines. Furthermore, the distal region was found to be functional in promoting gene transcription following exposure of RTH-149 cells to hydrogen peroxide.
 ...
PMID:Structural and functional analysis of the rainbow trout (Oncorhyncus mykiss) metallothionein-A gene. 760 Nov 21

A 5'-flanking region (-2024 to +61) of the guinea pig liver transglutaminase gene and some 5'-deletion mutants were tested for promoter activity in human hepatoblastoma HepG2 cells treated with interleukin-6 (IL-6) by an assay of the transient expression of the chloramphenicol acetyltransferase reporter gene. The promoter activity of the 5'-flanking region introduced into the HepG2 cells was increased by IL-6.
 ...
PMID:Increase caused by interleukin-6 in promoter activity of guinea pig liver transglutaminase gene. 776 54

We examined the effect of interleukin-6 (IL-6) on the expression of transglutaminase in human hepatoblastoma HepG2 cells. Treatment of cells with IL-6 increased their transglutaminase activity in a time- and dose-dependent way. Dexamethasone strengthened the stimulation by IL-6. Half-maximum stimulation of transglutaminase activity in the cells occurred at a dose of 40 pM IL-6 regardless of the presence of dexamethasone. Based on its immunoreactivity, the transglutaminase induced was identified as tissue-type transglutaminase. Immunoblot analysis showed that the increase in transglutaminase activity was related to an increase in the amount of transglutaminase protein. Northern blot analysis with a cDNA probe specific for human tissue-type transglutaminase showed that exposure of HepG2 cells to IL-6 increased the mRNA level of the enzyme, and the increase was detectable 3 h after IL-6 was added. Induction of the mRNA was maximum between 10 and 14 h. The increase in the mRNA level was not blocked by the presence of cycloheximide, suggesting that the increase was independent of protein synthesis. Injections into mice of substances that induce inflammation such as turpentine and lipopolysaccharides increased the liver transglutaminase activity. These results indicated that transglutaminase may be involved in some biological processes in hepatocytes regulated by IL-6 signaling.
 ...
PMID:Expression induced by interleukin-6 of tissue-type transglutaminase in human hepatoblastoma HepG2 cells. 809 10

Thrombocytosis and fever are frequent symptoms in children with hepatoblastoma. Interleukin-6 (IL-6) has been shown to mediate thrombocytosis and an acute-phase reaction including fever. We therefore investigated samples from 14 untreated patients with hepatoblastoma for this cytokine and in addition for interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), all of which are known to induce IL-6 production. High serum levels of IL-6 were only found in 3/14 patients; the other cytokines were not detectable. In contrast, 12/14 tumors produced substantial amounts of IL-6 in primary cell culture, while IL-1 beta was found in 3/14 supernatants; IL-1 alpha and TNF-alpha were always negative. Immunoenzymatic staining of fresh tumors revealed that IL-6 is not produced by the tumor cells, but rather by surrounding fibroblasts and endothelial cells. In tumor cells only IL-1 beta, but neither IL-1 alpha, TNF-alpha nor IL-6, could be detected. In co-culture experiments with fibroblasts and endothelial cells, addition of hepatoblastoma cells enhanced IL-6 production. Including an IL-1 receptor antagonist abolished this effect incompletely. Our results suggest that tumor cells in hepatoblastoma induce IL-6 production in surrounding fibroblasts and endothelial cells by virtue of their endogenous secretion of IL-1 beta and supposedly some other, as yet unidentified, mediator.
 ...
PMID:Production of interleukin-1 beta and interleukin-6 in hepatoblastoma. 838 28

Corticosteroid-binding globulin (CBG) belongs to the superfamily of serine proteinase inhibitors which include alpha 1-antitrypsin, alpha 1-antichymotrypsin, and T4-binding globulin. Interleukin-6 (IL-6), the main mediator of the acute phase phenomenon, increases alpha 1-antitrypsin and alpha 1-antichymotrypsin synthesis and decreases T4-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells. This effect is predominantly at a transcriptional level. When Hep G2 cells were exposed to different concentrations of IL-6 for variable time intervals, IL-6 caused a dose- and time-dependent decrease in the amount of [35S]methionine-labeled CBG immunoprecipitated in the culture medium. This effect could be greatly reduced by preincubation of IL-6 with its neutralizing antibody and reversed by removing the cytokine from the culture medium. The secretion rate of CBG was not affected by cell exposure to IL-6. CBG mRNA steady state levels were reduced; changes in mRNA were quantitatively similar to changes in secreted protein. Nuclear run-off assays failed to show a change in the rate of transcription of the CBG gene. These data indicate that IL-6 diminishes CBG synthesis by Hep G2 cells acting at a posttranscriptional level, presumably through a reduced stability of mRNA. In view of the role of IL-6 in the inflammatory process and other acute phase phenomena, these data suggest that its effects on CBG synthesis might influence the bioavailability of cortisol indirectly and play a role in regulating the homeostatic process during these conditions.
 ...
PMID:Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells. 839 24

In chronic inflammation it is reported that serum iron is depleted and hepatic iron is increased because of reticuloendothelial system iron blockade. However, recent studies indicate that hepatic parenchymal cells increase the uptake of transferrin-bound iron after in vivo stimulation with bacterial lipopolysaccharide, suggesting that endotoxemia itself or lipopolysaccharide-induced production of inflammation-related cytokines may also be responsible for this phenomenon. In this study the actions of inflammation-related cytokines on the synthesis of iron-binding proteins (transferrin and ferritin) and transferrin receptor and the uptake of transferrin-bound iron were investigated in a human hepatoblastoma cell line, HepG2, which is the most commonly used cell line for examining the regulation of hepatic protein synthesis by cytokines. The cells were exposed to interleukin-1 beta, interleukin-6 or tumor necrosis factor-alpha separately for 24 hr. In each cytokine treatment group, the level of transferrin, which is secreted into the conditioned medium, was found to be decreased compared with that of untreated cells. On the other hand, the biosynthesis of ferritin was markedly elevated after the same treatment. This increase in ferritin by cytokine treatment was diminished when deferoxamine was used concomitantly to deplete intracellular chelatable iron. After stimulation with interleukin-1 beta, interleukin-6 or tumor necrosis factor-alpha, 59Fe-labeled transferrin uptake into the cells was increased by 36%, 48%, or 18%, respectively, and this uptake was inhibited by the addition of excess unlabeled transferrin. A binding study with 125I-labeled diferric transferrin revealed that the three cytokines increased the number of transferrin receptors on the cell surface by 1.15-fold to 1.35-fold.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Regulation of iron metabolism in HepG2 cells: a possible role for cytokines in the hepatic deposition of iron. 840 63

Transglutaminase is a calcium-dependent enzyme that catalyzes an amine incorporation and a cross-linking of proteins. Intracellular transglutaminase is induced when human promyelocytic leukemia HL-60 cells are treated with retinoic acid and human hepatoblastoma HepG2 cells, with interleukin-6. To find whether the intracellular reaction catalyzed by transglutaminase increased when the enzyme is induced in these cells, the transglutaminase-catalyzed incorporation of 14C-labeled methylamine into cellular proteins was measured. The incorporation level of the labeled methylamine into proteins of HL-60 and HepG2 cells did not increase after the transglutaminase had been induced. The presence of the calcium ionophore A23187 did not affect these results. These findings suggested that even after the enzyme induction the catalytic action of intracellular transglutaminase is maintained at a constant level in these cells by unknown regulatory mechanism(s).
 ...
PMID:Analysis of catalytic action of transglutaminase induced in human promyelocytic leukemia (HL-60) and human hepatoblastoma (HepG2) cells. 898 79


1 2 Next >>