Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A polymerase chain reaction assay (Lust J.A. et al. (1992). Cytokine 4:96-100) was used to detect a mRNA coding for a soluble IL-6 receptor in human hepatoma cells. In addition to the expected amplification product, we found a sequence (SR4) which could be aligned to it with 78% identity. After cloning and sequencing a genomic 2.5-2.7 kB EcoRI fragment containing SR4, this sequence turned out to be part of a pseudogene corresponding to the transmembrane domain deleted soluble IL-6 receptor. Screening of a panel of interspecies hybrids revealed that it maps to chromosome 9.
 ...
PMID:Cloning and chromosomal localization of a pseudogene corresponding to a mRNA for a soluble IL-6 receptor. 757 86

Interleukin-6 receptor (IL-6R) is a member of the cytokine receptor superfamily characterised by the obligatory presence of WSXWS (Trp-Ser-X-Trp-Ser) sequence motif near the transmembrane domain. To more clearly understand the role of this motif, we treated the HepG2 hepatoma cell line with synthetic WSEWS peptide (E is glutamic acid) and checked the spontaneous and IL-6-induced production of acute-phase protein fibrinogen and C1-inhibitor (C1-INH). The peptide revealed a definitely stimulatory effect both on the constitutive synthesis of C1-INH and on the IL-6-induced fibrinogen synthesis of HepG2 cells. Monoclonal antibody specific for WSEWS pentapeptide was stimulatory for the spontaneous secretion of both fibrinogen and C1-INH. However, the IL-6-induced elevations of these acute-phase proteins were oppositely regulated, since the anti-WSEWS monoclonal antibody was inhibitory on the production of fibrinogen induced by IL-6 but strongly augmented the IL-6 induced production of C1-INH. Our study indicates that the WSEWS motif is critical in the effect of IL-6 on the acute-phase protein production influencing either the ligand binding by the WSEWS-containing receptor molecule or the signal transduction.
 ...
PMID:The effect of WSEWS pentapeptide and WSEWS-specific monoclonal antibodies on constitutive and IL-6 induced acute-phase protein production by a human hepatoma cell line, HEPG-2. 759 Sep 17

The role of the inflammatory cytokines on glucocorticosteroid binding (GCSB) and glucocorticosteroid receptor (GR) level was studied. We incubated a B cell line--CESS--, a promonocytic cell line--U937--and a hepatoma cell line--HepG2--in the presence of varying concentrations of IL-1 beta, IL-6 and TNF-alpha for 24 hours. Glucocorticosteroid binding was determined by the method of "whole cell uptake," and characterized by Scatchard analysis. A considerable increase in the glucocorticosteroid binding was induced by all the three cytokines. Northern analysis of the glucocorticoid receptor expression demonstrates that the action of the cytokines is likely not pretranslational. Present data suggest that local imbalance in the ratio of these three cytokines in different pathological cases might influence the glucocorticosteroid sensitivity of the lymphocytes, monocytes and hepatocytes as target cells.
 ...
PMID:Cytokine networks and corticosteroid receptors. 766 75

The promoter regions of three IL-6 inducible genes, hemopexin (Hpx), haptoglobin (Hp) and C-reactive protein (CRP) contain cis-acting IL-6 responsive elements (IL-6REs) which are necessary and sufficient to induce IL-6 transcription activation. Transcription factors of the C/EBP family interact with IL-6REs. Among these, IL-6DBP/NF-IL6 plays a key role in IL-6 signal transduction because its trans-activation potential is induced by IL-6 in the human hepatoma cell line Hep3B. We show here that a different C/EBP-related factor, C/EBP delta/NF-IL6 beta, is the major IL-6 induced protein interacting with IL-6REs in the nuclei of Hep3B cells. In contrast to IL-6DBP/NF-IL6, whose activity in Hep3B cells is modulated by IL-6 via a post-translational mechanism, C/EBP delta/NF-IL6 beta is transcriptionally induced by IL-6. Another contrasting feature is that the C/EBP delta cDNA transfected in Hep3B cells activates transcription from an IL-6RE synthetic promoter in a constitutive manner which is not further enhanced by IL-6. Therefore, in Hep3B cells, two distinct members of the C/EBP family are recruited in the IL-6 signal transduction pathway via different mechanisms.
 ...
PMID:The two C/EBP isoforms, IL-6DBP/NF-IL6 and C/EBP delta/NF-IL6 beta, are induced by IL-6 to promote acute phase gene transcription via different mechanisms. 768 Jan 15

Subconfluent monolayers of human hepatoma HepG2 cells were cultured for 2 days in serum-free DMEM containing 1 microM dexamethasone and human recombinant hepatocyte growth factor (HGF), retinoic acid (RA), IL-1, IL-6, LIF and mixtures of these factors. Incorporation of labelled thymidine was significantly decreased by IL-6, IL-1 and HGF but only slightly by LIF and RA. Synthesis of acute phase proteins secreted daily to the media was measured by electroimmunoassay with monospecific antisera. In addition, the synthesis and secretion of some proteinase inhibitors (alpha-1-proteinase inhibitor, alpha-1-antichymotrypsin, C1-inactivator, plasminogen activator inhibitor-1, inter-alpha-trypsin inhibitor and pre-alpha-inhibitor) was evaluated by incorporation of labelled methionine and fluorography. Among the cytokines tested IL-6 was the most potent regulator of acute phase protein synthesis. Hepatocyte growth factor stimulated basal synthesis of alpha-1-antichymotrypsin, and to a lesser extent affected some other proteins. Retinoic acid preferentially increased synthesis of alpha-1-antichymotrypsin, ceruloplasmin and plasminogen activator inhibitor-1. Both HGF and RA slightly modulated cytokine-induced synthesis of several acute phase proteins in HepG2 cells.
 ...
PMID:Regulation of synthesis of some proteinase inhibitors in human hepatoma cells HepG2 by cytokines, hepatocyte growth factor and retinoic acid. 768 88

The cytokines, IL-1 beta, TNF-alpha, IL-6, IL-11, leukemia inhibitory factor, and ciliary neurotrophic factor, stimulate the expression of specific sets of acute phase plasma proteins in the rat hepatoma H-35 cell line. In this paper, the experimental drug suramin is shown to inhibit in a dose-dependent fashion the cell response to these cytokines, with the exception of TNF-alpha. The action of the IL-6-type cytokines is more sensitive to suramin inhibition that that of IL-1 beta. The effect of suramin is detectable within 30 min at the level of gene transcription and appears to be mediated by the impairment of receptor function and/or signal transduction, rather than by the inhibition of nucleic acid polymerases or DNA topoisomerase II. Similar analysis of human hepatoma HepG2 cells indicated a several-fold higher resistance to suramin and in inhibition that was less cytokine-specific than in H-35 cells. The data suggest that suramin has the potential not only to modulate the proliferation or differentiation of tumor cells as described previously, but also to affect a differentiated cell function. This broad pleiotropic action has to be taken into consideration when applying suramin as a therapeutic agent.
 ...
PMID:Suramin inhibits the stimulation of acute phase plasma protein genes by IL-6-type cytokines in rat hepatoma cells. 768 32

Pancreatic secretory trypsin inhibitor (PSTI) has been suggested to be an acute-phase reactant in humans and to be induced by inflammatory cytokines such as the interleukins IL-1 and IL-6. We report that PSTI is synthesized in hepatoma cells and that the gene expression is augmented by IL-6. The start points (tsp) for basal and augmented transcription are exactly the same as the tsp in normal pancreas. Analysis of the PSTI gene revealed that a 40-bp DNA fragment located between kb -3.84 and -3.80 carries the element responsible for both transcriptional activity and IL-6-induced gene expression. This 40-bp fragment contains TTGNNGNAATG, the consensus sequence for the NF-IL6-binding site, which is also known as the IL-6-responsive element that is conserved among various acute-phase genes. The basal activity was augmented by another sequence that lies between kb -4.0 and -3.9.
 ...
PMID:Identification of the IL-6-responsive element in an acute-phase-responsive human pancreatic secretory trypsin inhibitor-encoding gene. 769 87

The three chains of the human complement component C8-alpha, beta and gamma- are encoded by distinct structural genes. C8A and C8B are closely linked on chromosome 1p and C8G is located on chromosome 9q. The biosynthesis and regulation of the gene products were studied in the human hepatoma-derived cell line HepG2 after in vitro induction of the acute-phase response by incubation with the cytokine interleukin IL-6. Analysis of C8 expression by immunoprecipitation and SDS-PAGE of biosynthetically labeled alpha-gamma and beta subunits demonstrated a positive response to this cytokine. The expression pattern observed in the hepatoma cells characterizes C8 in vitro as a positive acute-phase protein. In addition, the comparison of the relative amounts of the C8 transcripts provides evidence for a post transcriptional regulation of the C8 beta subunit. No evidence was obtained for an increased expression of IL-6 or IL-6 receptor mRNA thus excluding autoregulatory mechanisms of the cytokine in HepG2 cells.
 ...
PMID:Expression of the complement C8 genes during interleukin-6-mediated in vitro induction of the acute-phase response. 771 Jul 65

The gene regulatory functions of the human IL-2 receptor (IL-2R) were reconstituted in transiently transfected hepatoma cells. The combination of IL-2R beta and -gamma mediated a strong stimulation via the cytokine response element of the alpha 1-acid glycoprotein gene and the hematopoietin receptor response element, but none via the IL-6 response element or the sis-inducible element. IL-2R alpha enhanced 10-fold the sensitivity of the IL-2R beta.gamma complex to respond to IL-2 or IL-15, but did not modify the specificity or the magnitude of maximal gene regulation. A homodimerizing chimeric receptor G-CSFR-IL-2R beta could mimic the IL-2R action. The IL-2R-mediated gene regulation was similar to that seen with receptors for IL-4 and IL-7, but differed from that for IL-6 type cytokines, thrombopoietin, erythropoietin, and growth hormone. The activation of STAT proteins by the IL-2R was assessed in transfected L-cells and COS-1 cells. Although IL-2R subunits were highly expressed in these cells, no STAT protein activation was detectable. Transient overexpression of JAK3 was unable to change the signaling specificity of the hematopoietin receptors in rat hepatoma, L-, and COS cells, but established a prominent activation of the IL-6 response elements by the IL-2R and IL-4R in HepG2 cells. The data support the model that the IL-2R and related hematopoietin receptors produce at least two separate signals which control gene expression.
 ...
PMID:The action of interleukin-2 receptor subunits defines a new type of signaling mechanism for hematopoietin receptors in hepatic cells and fibroblasts. 771 38

The synthesis of some class 1 acute-phase proteins (APP), including C-reactive protein (CRP) and serum amyloid A (SAA) protein is completely blocked by the IL-1 receptor antagonist (IL-1Ra), whereas the production of fibrinogen, a class 2 APP, is increased by IL-1Ra in hepatoma cells, but this has never been tested in human hepatocytes in primary culture. Since previous studies on the contributions of cytokine inhibitors in connective tissues diseases suggested that IL-1 and tumour necrosis factor-alpha (TNF-alpha) might play an important role in the regulation of CRP, we decided to examine in more detail the respective roles of IL-1 beta, IL-6, and TNF-alpha and their inhibitors in the production of APP by human primary hepatocytes versus the hepatoma cell line PLC/PRF/5. In the hepatoma cell line, IL-1 beta and/or TNF-alpha had synergistic effects with IL-6 on the production of CRP and SAA. In contrast, these cytokines were devoid of effect in normal hepatocytes. The production of fibrinogen was increased by IL-6 and decreased by IL-1 (and TNF-alpha) in both cell types. The secretion of CRP and SAA by primary hepatocytes incubated with a cytokine-rich mononuclear cell-conditioned medium was totally unaffected by IL-1Ra or anti-TNF-alpha antibodies. In contrast, the addition of IL-1Ra increased the production of fibrinogen by both hepatoma cells and primary hepatocytes incubated with the mononuclear cell-conditioned medium. We therefore conclude that IL-1 beta and TNF-alpha do not exert any significant effect on the synthesis of CRP and SAA by human primary hepatocytes.
 ...
PMID:IL-1 receptor antagonist (IL-1Ra) does not inhibit the production of C-reactive protein or serum amyloid A protein by human primary hepatocytes. Differential regulation in normal and tumour cells. 774 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>