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)

The human glycoprotein hormone alpha-gene is transcriptionally activated by cAMP in placental cells. We have shown that the novel hypothalamic peptide, pituitary adenylate cyclase activating polypeptide, PACAP-38, significantly stimulates intracellular cAMP levels (12-fold increase; P < 0.001) in JEG-3 choriocarcinoma cells. Regulation of alpha-promoter activity was assessed using both the chloramphenicol acetyl transferase (CAT) and the luciferase (LUC) reporter gene systems. alpha-CAT activity was significantly stimulated by PACAP-38 (4-fold increase; P < 0.05) at 24 h with a similar stimulation being seen with a LUC expression vector. The kinetics of stimulation of the alpha-promoter by PACAP-38 were similar to those seen with 8-Br-cAMP and vasoactive intestinal polypeptide (VIP), a peptide which shares 68% homology with PACAP-38. PACAP-38 also stimulated the production of IL-6 from JEG-3 cells with a time course of response similar to that of alpha-promoter transcription. We conclude that human placental choriocarcinoma cells possess functional receptors for PACAP-38, whose activation enhances cAMP formation, alpha-subunit gene transcription and interleukin-6 (IL-6) production.
 ...
PMID:PACAP-38 positively regulates glycoprotein hormone alpha-gene expression in placental cells. 751 49

IL-6 signal transduction occurs when the liganded interleukin-6 receptor (IL-6R) interacts with glycoprotein (gp) 130. We hypothesized that synthetic peptides modeled from the extramembranous domain of the IL-6R may interfere with the IL-6-induced reaction between IL-6R and gp130 and may serve to elucidate the initial steps in IL-6 signal transduction. The capacity of such peptides to modulate two different IL-6 functions was evaluated: 1) IL-6-dependent B9 cell mitogenesis, and 2) IL-6-induced acute phase protein synthesis in HepG2 cells. A synthetic peptide, 249Y16T264, corresponding to residues 249-264, inhibited IL-6-dependent B9 proliferation and IL-6-induced acute phase protein up-regulation in HepG2 cells. Other peptides modeled from different regions of the IL-6R were not inhibitory. 249Y16T264 did not inhibit IL-6-independent HepG2 cell proliferation or total cellular protein synthesis. The inhibitory effect was reversible, indicating that the peptide was not cytotoxic. 249Y16T264 did not inhibit 125I-IL-6 binding in U266 cells. Delineation of this domain identified 249Y10R258 as the minimum effective sequence capable of inhibiting fibrinogen synthesis. Amino acid substitutions in 249Y10R258 obliterated the inhibitory effect on fibrinogen synthesis. In conclusion, a region of the extramembranous domain of the IL-6R has been identified that is involved in the regulation of IL-6 signal transmission. A synthetic peptide representing this region inhibits IL-6-dependent B9 cell mitogenesis and IL-6-stimulated acute phase response in HepG2 cells without affecting ligand binding.
 ...
PMID:Identification of a regulatory domain of the interleukin-6 receptor. 751 15

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates proliferation and differentiation of progenitor cells of neutrophils by signaling through its receptor (G-CSFR). Although the G-CSFR belongs to the cytokine receptor superfamily, which lacks an intracellular kinase domain, G-CSF-induced tyrosine phosphorylation of cellular proteins is critical for its biologic activities. We report here that JAK1 and JAK2 tyrosine kinases are tyrosine phosphorylated in response to G-CSF induction. We also demonstrate that the DNA-binding protein STAT3 (also called the acute-phase response factor [APRF], activated by interleukin-6) is an early target of G-CSF-induced tyrosine phosphorylation. G-CSF induces two DNA-binding complexes; the major complex contains tyrosine phosphorylated STAT3 protein and the minor complex appears to be a heterodimer of the STAT1 (previously p91, a component of DNA-binding complexes activated by interferons) and STAT3 proteins. Antiphosphotyrosine antibody interferes with the DNA binding activity of activated STAT3, indicating that tyrosine phosphorylation of STAT3 is important for the DNA binding activity. These results identify a signal transduction pathway activated in response to G-CSF and provide a mechanism for the rapid modulation of gene expression by G-CSF.
 ...
PMID:Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor. 752 88

High serum level of bioactive interleukin-6 (IL-6) is regarded as a predictor of poor prognosis in multiple myeloma (MM). On the other hand, the reported levels of immunoreactive IL-6 have been highly variable, and the prognostic value of immunoreactive IL-6 in MM is not clear. We have analyzed the prognostic significance of serum immunoreactive IL-6, as measured by a sensitive immunosorbent assay, in 210 patients with newly diagnosed MM subsequently treated with intermittent melphalan and prednisone. The serum levels of acute phase proteins C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein (orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP, alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the patients, respectively. There was a significant correlation between the clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P = .001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the patients were alive. Univariate logistic regression analysis showed that high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM (P = .007), beta 2-microglobulin (beta 2M; P < .001), and thymidine kinase (P < .05) were all associated with 3-year mortality. In multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P = .01) had independent prognostic significance. The patients with high levels of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying within 3 years from diagnosis (16% and 21% of the patients in these groups were alive, respectively). When the patients were stratified according to the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT was especially evident in stage II patients. When the patients were divided into two groups according to normal or raised serum IL-6 levels, the patients with high IL-6 levels had more frequent osteolytic bone lesions (P = .03) and a more aggressive disease. We conclude that serum immunoreactive IL-6 is a significant prognostic marker in MM.
 ...
PMID:Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group. 753 May 7

Serum levels of alpha 1-antichymotrypsin (alpha 1-ACT) were measured in patients with early and late onset Alzheimer's disease (e-AD, 1-AD), patients with vascular dementia (VD) and healthy elderly. Patients with 1-AD were divided into two groups, one had normal alpha 1-ACT values and one had increased serum levels of alpha 1-ACT. Other acute phase proteins were also measured. The serum levels of alpha 2-macroglobulin (alpha 2-MG), alpha 1-antitrypsin (alpha 1-AT), ceruloplasmin (CER), transferrin (TRSF) and alpha 1-acid glycoprotein (alpha 1-ac.GL) were within the normal range. The C reactive protein (CRP) was occasionally detectable at low concentrations in e-AD, in both groups of 1-AD patients and in VD patients. Low serum concentrations of interleukin-6 (IL-6) were found in a higher proportion of 1-AD than in patients with e-AD or VD. These results indicated that increased levels of alpha 1-ACT along with occasional detection of IL-6 might be peripheral markers of the 'acute reaction' in the brain.
 ...
PMID:Increased serum alpha 1-antichymotrypsin in patients with probable Alzheimer's disease: an acute phase reactant without the peripheral acute phase response. 753 91

The synthesis of the human acute-phase alpha 1-acid glycoprotein (AGP) is primarily controlled by IL-6 and IL-1 in liver cells. In the present study, monoclonal antibodies against human gp80 interleukin-6 receptor (IL-6R) were utilized to study the role of the IL-6R in the control of the IL-6-induced AGP synthesis in the human hepatoma Hep3B cell line. Two of the 4 MAbs used in this study, M164 and M195, identified 2 different epitopes involved in IL-6 binding and two others, M91 and M182, recognized epitopes not involved in IL-6 binding. Dose-response experiments indicated that up to 55% of AGP synthesis was inhibited by 10(5) ng/ml of MAbs 164 or 195 when Hep3B cells were treated by IL-6 for 48h. Kinetics of the inhibition of AGP synthesis after addition of anti-IL-6R indicated that the decrease of the IL-6-induced AGP synthesis by Hep3B cells was obtained immediately after the addition of the anti-IL-6R MAbs. Of the two MAbs not involved in IL-6 binding, M91 was unable to interfere with the IL-6-induced AGP synthesis whereas, surprisingly, M182 decreased it by about 25%. Since M182 was also able to interfere with the proliferative response of an IL-6 dependent plasma cell line, our results suggested that M182 may be directed to a structure involved in the IL-6/IL-6R gp130 complex formation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:IL-6-induced changes in synthesis of alpha 1-acid glycoprotein in human hepatoma Hep3B cells are distinctively regulated by monoclonal antibodies directed against different epitopes of IL-6 receptor (gp80). 753 7

Rat hepatoma cells H-35 cultured in serum-free medium were exposed to interleukin-6 (IL-6), interleukin-1 (IL-1), hepatocyte growth factor (HGF), retinoic acid (RA), or a mixture of these factors. Production of acute phase proteins, responding to IL-6 alone (type 2) or to the mixture of IL-6 and IL-1, was assessed by electroimmunoassay and the corresponding mRNAs were compared by Northern blot analysis. HGF enhanced IL-6-induced synthesis of alpha-2-macroglobulin but reduced synthesis of C3 complement and alpha-1-acid glycoprotein. Retinoic acid reduced the response to IL-6 of alpha-2-macroglobulin but enhanced that of alpha-1-acid glycoprotein and especially of C3 complement. In general, changes in protein secretion were correlated with the contents of their corresponding cellular mRNAs. These results indicate that hepatocyte growth factor can enhance basal or IL-6-induced gene expression of type 2 and reduce the expression of type 1 acute phase proteins, whereas the action of retinoic acid is opposite. The modulation of acute phase response by HGF and RA likely involves transcriptional factors and regulatory sequences in the genes coding for these two types of acute phase proteins.
 ...
PMID:Hepatocyte growth factor and retinoic acid exert opposite effects on synthesis of type 1 and type 2 acute phase proteins in rat hepatoma cells. 753 94

1. Smoking exerts an inflammatory stimulus on lung macrophages, and smokers generally have low intakes of antioxidant micronutrients. This study was performed to investigate the relationship between whole-blood tumour necrosis factor production, plasma interleukin-6 and acute-phase protein concentration and antioxidant vitamins in smokers and non-smokers. 2. Measurement of tumour necrosis factor was conducted in whole blood stimulated with endotoxin (lipopolysaccharide), and interleukin-6 concentrations were measured in the plasma of smokers and non-smokers. Enzyme and dietary antioxidant concentrations and acute-phase proteins were determined in the two groups. 3. Tumour necrosis factor production and plasma interleukin-6 concentrations were 38% (P = 0.01) and 16% (P = 0.07) greater, respectively, in smokers than in non-smokers. Plasma vitamin A and E concentrations were unaffected by smoking; however, a 21% lower plasma vitamin C (P = 0.04) concentration was observed in smokers, than in non-smokers despite a similar intake of this vitamin by the two groups. 4. Concentrations of the acute-phase proteins alpha 1-acid glycoprotein, caeruloplasmin and alpha 2-macroglobulin were increased in the plasma of smokers compared with non-smokers by 39%, 28% and 12% respectively (P < 0.01). Our studies indicate that smokers have a compromised antioxidant status and elevated concentrations of tumour necrosis factor and interleukin-6 as a consequence of smoking. 5. These observations may provide some insight into the biological mechanisms underlying the pathology associated with smoking.
 ...
PMID:Cigarette smoking influences cytokine production and antioxidant defences. 754 May 25

The acute-phase response is the answer of the organism to a disturbance of its homeostasis and is characterized by dramatic changes in the concentration of some plasma proteins defined as acute-phase proteins. In recent years several data have shown that interleukin-6 (IL-6) is the major inducer of acute-phase protein synthesis in human hepatocytes. Recently, we demonstrated higher IL-6 serum levels in head and neck cancer (HNC) patients than in healthy subjects. In the present study we examined the relationship between levels of IL-6 and of several acute-phase proteins, including C-reactive protein (CRP), alpha 1-antitrypsin (ATT), alpha 1-acid glycoprotein (AAG), haptoglobin (HPT) and fibrinogen. Eighteen patients were studied and had squamous cell carcinoma of the larynx (n = 9), oral cavity (n = 4), oropharynx (n = 3) and hypopharynx (n = 2). Proteins were measured at three time points before and three time points after surgery. Significant (P < 0.0001) relationships were found between IL-6 and CRP (r = 0.69), and fibrinogen (r = 0.51), whereas no correlation was found with AAT (r = 0.13, P = 0.56), AAG (r = 0.38; P = 0.07) and HPT (r = 0.16; P = 0.46). These data strongly suggest that IL-6 may play a key role in acute-phase protein synthesis in HNC and in regulation of the complex host response to malignancies.
 ...
PMID:Interleukin-6 and acute-phase proteins in head and neck cancer. 754 87

The effects of nicotinamide on hepatocyte viability and secretion of albumin and alpha 1-acid glycoprotein were studied in the absence or presence of dexamethasone and/or recombinant human interleukin-6 either after cell attachment (2 h) or after 24, 48, and 72 h of culture. The evolution of hepatocyte survival during the culture was appreciated by measurement of total DNA content. The secretion of albumin and alpha 1-acid glycoprotein was measured after a 4-h period following cell attachment or after 24, 48 and 72 h of culture. The important decrease of DNA content, mRNA levels and secretion of albumin and alpha 1-acid glycoprotein in control cultures after 2-3 days was not prevented by the addition of nicotinamide. In contrast, dexamethasone alone or with recombinant human interleukin-6 improved DNA content and albumin secretion with no additional effect of nicotinamide. The secretion of alpha 1-acid glycoprotein was largely induced by dexamethasone alone or dexamethasone and recombinant human interleukin-6. The increase of alpha 1-acid glycoprotein secretion was not modified by the addition of nicotinamide and averaged respectively 27- and 60-fold for dexamethasone alone and dexamethasone and recombinant human interleukin-6 after 48 h. These observations suggested that nicotinamide, at least in the conditions tested here, is unable to prevent alterations of hepatocyte viability and gene expression of cultured hepatocytes.
 ...
PMID:Effects of nicotinamide on hepatocyte viability and secretion of albumin and alpha 1-acid glycoprotein by adult rat hepatocytes in primoculture. Comparison with dexamethasone and recombinant human interleukin-6. 754 7


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