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)

We have investigated whether parotin subunit (PS) and its partial synthetic peptide (P-10.2: TDDTAIVLLK), possess interleukin 1 (IL-1)-like activities, and act on cell lines other than lymphocytes. When Chang liver cells were cultured with P-10.2, PS or IL-1, P-10.2 and PS augmented the growth of Chang liver cells. On the other hand, IL-1 enhanced the growth of Change liver cells at 1 day of the initial culture and subsequently failed to enhance during at least 4-day incubation. Next, effects of P-10.2 and PS on the growth of Alexander cells and MH134 were investigated. The proliferation of Alexander cells was inhibited with P-10.2 or PS but not with IL-1. P-10.2 inhibited the growth of MH134 at day 1 and 3, while the growth of MH134 was shown not to be inhibited with PS and IL-1 at day 1, but rather suppressed them at day 3. These results suggest that P-10.2 augments the growth of non-malignant liver cells (Chang liver cells) but inhibits that of hepatoma cells (Alexander cells and MH134). P-10.2 enhanced fibrinogen and hepatoglobin secretion from Chang liver cells. In addition to their liver cell activation, P-10.2 and PS stimulated ACTH and beta-endorphin secretion from AtT-20 cells.
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PMID:Parotin subunit and its synthetic peptide possess interleukin 1-like activity and exert stimulating effects on liver cells and brain cells. 805 82

In patients with the anemia of chronic diseases, the plasma level of EPO is often low in relation to the blood hemoglobin concentration. Because infectious and inflammatory processes cause activation of cytokine-producing macrophages and lymphocytes, we investigated whether isolated inflammatory cytokines influence the synthesis of EPO in vitro. IL-1 and TNF-alpha were shown to inhibit EPO mRNA levels and EPO formation in the human hepatoma cell cultures HepG2 and Hep3B, and to lower EPO formation in isolated perfused rat kidneys. IFN-alpha and IFN-beta also induced some inhibition of EPO production in HepG2 cultures. IL-3, TGF-beta 2, and IFN-gamma did not inhibit. IL-6 stimulated the production of EPO in Hep3B cells but was ineffective in HepG2 cells and lowered EPO production in isolated perfused rat kidneys. IL-1, TNF-alpha, and possibly other cytokines could contribute to defective EPO production in renal and nonrenal immune responses.
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PMID:Inhibition of erythropoietin production by cytokines. Implications for the anemia involved in inflammatory states. 818 37

Mannose-binding protein (MBP) is a plasma protein synthesized by hepatocytes. MBP, a structural analogue of the complement component C1q, can activate complement via the classical pathway and plays an important role in host defence. Expression of the human MBP gene was studied using the human hepatoma cell line HuH-7. RNA extracted from HuH-7 cells was reverse-transcribed to cDNA, amplified by the polymerase chain reaction and analysed by Southern blot hybridization. MBP mRNA expression in HuH-7 cells was increased by interleukin-6 (IL-6), dexamethasone and heat shock, decreased by interleukin 1 (IL-1), and unaffected by interferon gamma (IFN gamma), tumour necrosis factor alpha (TNF alpha) and transforming growth factor beta (TGF beta). Gel shift assays demonstrated Sp-1 binding sites in the 5' region of the gene, and formation of specific complexes between DNA and nuclear protein extracted from HuH-7 cells treated with IL-1 or IL-6. Human MBP is an acute-phase protein, and transcription of its gene is enhanced by IL-6, dexamethasone and heat shock but inhibited by IL-1. The actions of the cytokines appear to be mediated by specific transcription factors.
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PMID:Human mannose-binding protein gene is regulated by interleukins, dexamethasone and heat shock. 825 72

C-Reactive protein (CRP) is a minor acute phase reactant (APR) in the mouse, whereas CRP is the prototypical and one of the major positive APRs in all other mammals. MoCRP gene expression was tissue specific for the liver and induced by culture supernatants of LPS-activated macrophages. MoCRP gene expression by isolated hepatocytes in culture increased c, 3-fold in response to interleukin (IL)-1, but not IL-6. IL-6 is the most potent inflammatory cytokine for the induction of human CRP and many other APRs. By contrast, gene expression of the major APR of the mouse, serum amyloid P-component (SAP), a structural homologue of CRP, increased in response to either IL-1 or IL-6 under the same conditions. The region containing two potentially IL-1 responsive C/EBP elements in the moCRP gene failed to respond to IL-1 when a pCAT construct containing the elements was transfected into Hep 3B2 hepatoma cells. Therefore, IL-1 may influence the expression of the moCRP gene at the post-transcriptional rather than at the transcriptional level. The findings suggest that moCRP may be a minor APR because of the limited response of the gene to inflammatory cytokine signals.
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PMID:The mouse C-reactive protein (CRP) gene is expressed in response to IL-1 but not IL-6. 826 May 97

Although expression of the haptoglobin (HP) as an acute phase reactant is evolutionarily conserved among mammals, there are differences among species with regard to the hormones required for stimulation. Using primary hepatocyte cultures, we show that in Mus caroli, as in rat, IL-1 and IL-6 are stimulatory, whereas in M. domesticus, as in humans, IL-1 response is diminished. In vivo, an acute inflammatory process increases hepatic HP expression in both mouse species up to 30-fold but minimally affects the low level HP expression in the lung. To define the species-specific differences in regulation, we isolated the hormone-responsive elements of the HP gene from the Mus species, M. domesticus, M. caroli, and M. saxicola. Functional studies in transfected hepatoma cells revealed an exceptionally strong dexamethasone response for all three murine HP gene elements. The IL-6 response was less prominent than in rat or human. A modest response to IL-1 was observed in M. caroli and M. saxicola. A mouse-specific insertion of a polypurine sequence led to a binding site for the PEA3 transcription factor in the HP gene promoter of M. domesticus and M. saxicola, but not M. caroli. The specific regulatory effects of glucocorticoid receptor, C/EBP beta, and Ets proteins were documented by co-transfection.
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PMID:Species-specific changes in regulatory elements of mouse haptoglobin genes. 829 78

A cDNA encoding the human homologue of mouse RYK (related to receptor tyrosine kinases) has been cloned from an interleukin 1 (IL-1)-stimulated human hepatoma cDNA library by cross-species hybridization using the mouse RYK cDNA as a probe. The sequence of the 3067-bp cDNA clone encoding human RYK predicts a transmembrane protein with a cytoplasmic domain that contains the consensus sequences (subdomains I-XI) of the protein tyrosine kinase (PTK) family. The highly conserved motif -D-F-G- (subdomain VII) of the catalytic domain of other receptor-type tyrosine kinases is altered to -D-N-A- in human RYK. In addition, a number of other changes were found in the ATP binding site (subdomains I and II) and the motif [-I-H-R-D-L-A-A-R-N-] found in subdomain VI. Comparison of the human and mouse RYK sequences shows a 92% conservation at the nucleotide level and 97% at the amino acid level. There was no significant homology between the extracellular domain of RYK and the other families of receptor tyrosine kinases described to date. RYK therefore appears to define a new subclass of receptor-type tyrosine kinases whose structure has remained highly conserved across species.
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PMID:Molecular cloning and chromosomal localisation of the human homologue of a receptor related to tyrosine kinases (RYK). 838 29

The HuH-7 human hepatoma cell line was stimulated by IL-1 and IL-6 to increase the synthesis of acute-phase proteins, e.g. serum amyloid A (SAA), alpha 1 antichymotrypsin (ACT), alpha 1-protease inhibitor, alpha 1 acid-glycoprotein and haptoglobin, with the exception of the pentraxins (serum amyloid P and C-reactive protein). Haptoglobin and ACT were stimulated by IL-1 which has not been observed in some other hepatoma cell lines. The concentration of IL-1 required for stimulation of SAA was higher than that required for haptoglobin stimulation. IL-1 receptor antagonist was capable of inhibiting these responses and acted at a lower concentration to inhibit SAA than required to inhibit ACT or haptoglobin induction. Transforming growth factor beta (TGF beta) was also able to inhibit the response to IL-1 but had no effect on acute-phase protein responses to IL-6.
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PMID:Inhibition of the acute-phase response in a human hepatoma cell line. 839 Dec 2

Hepatocytes respond to inflammatory stimuli by changing the synthesis and N-glycosylation of acute phase plasma proteins (APP). So far, interleukin (IL) 6, transforming growth factor beta (TGF beta), tumor necrosis factor alpha (TNF) and IL-1 have been found to control N-glycosylation patterns of APP. Cytokines either increased (type I) or decreased (type II) the ratio of bi-relative to more branched N-glycans on APP. In this study, we describe the effect of leukemia inhibitory factor (LIF), interferon gamma (INF gamma) and dexamethasone (dex) on production of alpha 1-protease inhibitor (PI) and alpha 1-antichymotrypsin (ACT) and on glycosylation of PI in the human hepatoma cell line HepG2. Cytokines and dex were used separately and in various combinations including also IL-6 and TGF beta. Production of the antiproteases was quantitated by immunoelectrophoresis of the proteins accumulated in the culture medium. Glycosylation pattern of PI was assessed by crossed immunoaffinity electrophoresis (CIAE) with Concanavalin A (Con A) as a ligand. The production of ACT and PI was increased by LIF, decreased by INF gamma and unaffected by dex. LIF and INF gamma each like IL-6, decreased PI-Con A reactivity while dex like TGF beta enhanced PI-Con A reactivity. Combination of dex with LIF yielded additive effects while combination of dex with either INF gamma, L-6 or TGF beta acted synergistically on PI-Con A reactivity. Combinations of multiple cytokines and dex produced additive, inhibitory or synergistic effects. The type of glycosylation profile of PI secreted by HepG2 cells depended on the composition and amounts of interacting cytokines and dex.
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PMID:Leukemia inhibitory factor, interferon gamma and dexamethasone regulate N-glycosylation of alpha 1-protease inhibitor in human hepatoma cells. 839 65

Early and severe loss of body weight associated with pronounced tissue changes developed in rats transplanted with a fast-growing ascites hepatoma (Yoshida AH-130). The protein content showed an early and marked fall in the skeletal muscle, while in the liver it transiently increased 4 days after implantation then declined to values lower than in control animals. Protein loss in gastrocnemius muscle and liver resulted mainly from enhancement of protein catabolism (Tessitore L. et al., Biochem. J., 241: 153-158, 1987). In contrast to the tumour-bearing rats, in the pair-fed animals the initial body weight was maintained, while the protein mass decreased sharply in the liver and moderately in the gastrocnemius muscle. In host animals total plasma protein decreased during the period of tumour growth, while both triglycerides and total cholesterol markedly increased. Glucose remained unchanged even when overt cachexia had developed. The total free amino acid concentration in the plasma of tumour-bearing rats decreased slightly by day 4 and returned to values close to those of controls in the late stages of tumour growth. By contrast, in the pair-fed controls the plasma levels of triglycerides and particularly of total free amino acids and glucose decreased over the whole experimental period, whereas total protein and cholesterol were unchanged. Marked perturbations in the hormonal homeostasis developed early after tumour transplantation. The plasma levels of glucagon, corticosterone and catecholamines rose sharply, while those of insulin and thyroid hormones decreased. Furthermore, high plasma concentrations of prostaglandin E2 (PGE2) and tumour necrosis factor (TNF) were observed over the whole experimental period. IL-1-like activity, TNF and PGE2 were released in vitro from AH-130 cells. These data suggest that the systemic effects of AH-130 tumour on the host rat reflected the interplay of a complex network of factors, including classical hormones and cytokines, all of which likely concur in enhancing tissue protein catabolism.
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PMID:Humoral mediation for cachexia in tumour-bearing rats. 842 75

Inflammation is accompanied by an increase in the plasma levels of a number of proteins collectively known as acute-phase reactants (APRs). Serum amyloid P component (SAP) is a major mouse APR: hepatic SAP mRNA and plasma SAP protein concentrations increase by up to 20-fold in mice undergoing an inflammatory response. In-vitro studies, using primary hepatocyte cultures, have previously shown that SAP mRNA and protein levels increase in response to stimulation with a variety of cytokines such as monocyte-conditioned medium (MCM), interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta). In this report, we have examined a mouse hepatoma cell line in which SAP gene regulation closely resembles that of primary hepatocytes. Accumulation of SAP mRNA in the +/+ Li mouse hepatoma cell line after stimulation with MCM, IL-1, IL-6 and the combination of IL-1 and IL-6 was demonstrated. This increase in the cellular content of SAP mRNA did not require new protein synthesis and was at least partially due to an increase in the transcription rate of the SAP gene.
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PMID:Regulation of mouse serum amyloid P gene expression by cytokines in vitro. 845 73


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