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

Interleukin-6 (IL-6) and insulin-like growth-factor-1 (IGF-1) are cytokines produced by a variety of cells that act on a wide range of tissues, influencing cell growth and differentiation. Purified plasma membranes from human U937 monoblastic cells produced in vitro dimeric species of IL-6- and IGF-1-derived peptides through the sequential actions of surface-associated enzymes cathepsin G and transpeptidase activities. Cathepsin G degraded native unglycosylated IL-6 and IGF-1 molecules into 8-kDa and 7-kDa peptides respectively. Subsequent dimerisation of these intermediate forms into 16-kDa IL-6- and 14-kDa IGF-1-derived peptides was inhibited by acivicin and glutathione which are specific inhibitors of the standard cell-surface gamma-glutamyl transpeptidase (gamma-GT). However U937 plasma membranes, cleared of gamma-GT activity by immunoprecipitation with anti-gamma-GT and adsorption on protein-G-Sepharose, were still able to convert the intermediate forms of IL-6 and IGF-1 into dimers. Together, these observations indicate that the transpeptidase involved in the formation of the dimeric species of IL-6 and IGF-1 was related to, but distinct from, standard cell-surface gamma-GT. Cells of all hematopoietic lineages expressed gamma-GT-related activity. In contrast to the 16-kDa IL-6-derived peptide that did not retain growth-stimulating activity, the 14-kDa IGF-1 peptide was at least equipotent with native IGF-1 in the BALB/c 3T3 fibroblast DNA synthesis response. The N/O-glycosylated IL-6 was clearly as sensitive to cathepsin-G- and gamma-GT-related activities as the unglycosylated IL-6 from Escherichia coli, thus indicating that the sugar chains did not protect the cleavage sites of the two proteases on the IL-6 molecule. Our in vitro findings raise the possibility that similar proteases participate in the regulation of the catabolism of IL-6 and IGF-1 in vivo.
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PMID:Protease-catalyzed conversion of insulin-like growth factor-1 and interleukin-6 into high-molecular-mass species through the sequential action of hematopoietic surface-associated cathepsin G and gamma-glutamyl transpeptidase-related activities. 791 87

Activated macrophages have been shown to exert cytostatic and cytotoxic effects toward tumor cells via nitric oxide (NO) release. In the CNS, microglial cells are considered to be the main resident population of immune effector cells. In this study, cytotoxic activity of N11, an immortalized murine microglial cell line, toward rat progressive DHD/PROb and regressive DHD/REGb colon carcinoma cells was examined in parallel with NO production. Cytotoxicity was evaluated using a novel method, the gamma-glutamyl transpeptidase (gamma-GTP) assay, based on the fact that DHD tumor cells expressed high levels of gamma-GTP activity, while no gamma-GTP activity was found in cells of the monocyte/macrophage lineage. Results showed that activation of N11 cells by interferon-gamma plus either lipopolysaccharide or tumor necrosis factor-alpha induced high amounts of NO release and cytotoxic effects toward DHD/PROb as well as DHD/REGb cells. NO release by activated N11 cells was augmented by addition of tumor cell-conditioned medium. Both NO release by N11 cells and cytotoxicity were blocked by addition of N(G)-monomethyl-L-arginine (L-NMA), an inhibitor of NO synthase, suggesting that cytotoxicity was mediated by N11-derived NO. However, in the presence of L-NMA an increased production of interleukin-6 was also observed. In conclusion, in opposition to information obtained with brain-derived endothelial cells, brain-derived microglial cells did not differentiate between progressive and regressive clones of colon carcinoma cells. Our results point to a specific role for both endothelial and microglial cell types in the context of brain metastasis. Microglial cells can be cytotoxic for tumor cells, and this cytotoxicity is mediated by NO.
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PMID:Microglial cells induce cytotoxic effects toward colon carcinoma cells: measurement of tumor cytotoxicity with a gamma-glutamyl transpeptidase assay. 900 56

Serum interleukin-6 (IL-6) levels were measured in 58 adult patients with newly diagnosed acute myelogenous leukemia (AML) using an ELISA method in order to find potential clinical correlations. Detectable average levels were 57 +/- 68 pg/ml and 52 patients (90%) had higher cytokine levels than normal donors. IL-6 levels (115 +/- 102 pg/ml versus 36 +/- 40 pg/ml, p = 0.0001) were higher in patients with fever of apparently non infectious origin, and higher levels were associated with higher percentage of blasts in the peripheral blood (R = 0.29, p = 0.04) and in the bone marrow (R = 0.39, p = 0.003), elevated serum LDH level (R = 0.36, p = 0.01), hyperbilirubinemia (R = 0.36, p = 0.008), elevated serum GGT level (R = 0.46, p = 0.003), and elevated serum GOT (R = 0.36, p = 0.008) and GPT levels (R = 0.44, p = 0.004). Highest IL-6 levels were observed in FAB M1 (86 +/- 112 pg/ml), M3 (73 +/- 69 pg/ml), and M6 (92 +/- 60 pg/ml) AML subtypes. Serum IL-6 levels in AML might be related to both non specific inflammatory reactions and the specific biology of the disease.
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PMID:Serum interleukin-6 levels in adult acute myelogenous leukemia: relationship with disease characteristics and outcome. 915 58

The hepatic ischemia-reperfusion syndrome was investigated in 28 patients undergoing elective partial liver resection with intraoperative occlusion of hepatic inflow (Pringle maneuver) using the technique of liver vein catheterization. Hepatic venous oxygen saturation (ShvO2) was monitored continuously up to 24 hours after surgery. Aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transpeptidase, pseudocholinesterase, alpha-glutathione S-transferase, reduced and oxidized glutathione, procalcitonine, and interleukin-6 were serially measured both before and after Pringle maneuver during the resection and postoperatively in arterial and/or hepatic venous blood. ShvO2 measurement demonstrated that peri- and postoperative management was suitable to maintain an optimal hepatic oxygen supply. As expected, we were able to demonstrate a typical enzyme pattern of postischemic liver injury. There was a distinct decrease of reduced glutathione levels both in arterial and hepatic venous plasma after LR accompanied by a strong increase in oxidized glutathione concentration during the phase of reperfusion. We observed increases in procalcitonin and interleukin-6 levels both in arterial and hepatic venous blood after declamping. Our data support the view that liver resection in man under conditions of inflow occlusion resulted in ischemic lesion of the liver (loss of glutathione synthesizing capacity with disturbance of protection against oxidative stress) and an additional impairment during reperfusion (liberation of reactive oxygen species, local and systemic inflammation reaction with cytokine production). Additionally, we found some evidence for the assumption that the liver has an export function for reduced glutathione into plasma in man.
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PMID:Hepatic ischemia-reperfusion syndrome after partial liver resection (LR): hepatic venous oxygen saturation, enzyme pattern, reduced and oxidized glutathione, procalcitonin and interleukin-6. 1287 55

Chronic bile duct ligation (BDL) is a useful model of cirrhosis. However, its parallel plasma and liver changes in levels of cytokines and nitric oxide (NO), involved in liver damage, remain unknown. The aims of this work were to quantify both the plasma and hepatic levels of five cytokines and NO in cirrhotic rats, 28 days after bile BDL, and to analyze their relationship with liver damage markers. One group of male Wistar rats was bile duct ligated and another group was sham operated, both groups were sacrificed 28 days after BDL. Plasma and liver cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, -1beta, -10 (IL-6, -1beta, -10) and interferon-gamma (IFN-gamma), were measured by ELISA. Plasma and hepatic NO was determined as NO(2)(-)+NO(3)(-) by an enzymatic method. Alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminotransferase and bilirubins were determined in plasma. Collagen, lipid peroxidation and glycogen were quantified in liver. Two histopathological staining techniques were performed. BDL-induced cirrhosis was corroborated by the elevated liver damage markers and histopathological analysis. Chronic BDL significantly increased (P<0.05) most of plasma and hepatic cytokine levels and diminished the hepatic IFN-gamma amount. NO was increased in both tissues, but such change was only significant in plasma. Biliary cirrhosis produces interesting changes in plasma and hepatic levels of cytokines and NO. This finding in chronic BDL model in rats has not been previously described in both tissues for such cytokines and NO. Cytokines and NO imbalance favor establishment and perpetuation of cirrhosis.
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PMID:Chronic bile duct obstruction induces changes in plasma and hepatic levels of cytokines and nitric oxide in the rat. 1661 7

Curcumin, an anti-inflammatory and antioxidant compound, was evaluated for its ability to suppress acute carbon tetrachloride-induced liver damage. Acute hepatotoxicity was induced by oral administration of CCl4 (4 g/kg, p.o.). Curcumin treatment (200 mg/kg, p.o.) was given before and 2 h after CCl4 administration. Indicators of necrosis (alanine aminotransferase) and cholestasis (gamma-glutamyl transpeptidase and bilirubins) resulted in significant increases after CCl4 intoxication, but these effects were prevented by curcumin treatment. As an indicator of oxidative stress, GSH was oxidized and the GSH/GSSG ratio decreased significantly by CCl4, but was preserved within normal values by curcumin. In addition to its antioxidants properties, curcumin is capable of preventing NF-kappaB activation and therefore to prevent the secretion of proinflammatory cytokines. Therefore, in this study we determined the concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) mRNA, and NF-kappaB activation. CCl4-administered rats depicted significant increases in TNF-alpha, IL-1beta, and IL-6 production, while curcumin remarkably suppressed these mediators of inflammation in liver damage. These results were confirmed by measuring TNF-alpha, and IL-1beta protein production using Western Blot analysis. Accordingly, these proteins were increased by CCl4 and this effect was abolished by curcumin. Administration of CCl4 induced the translocation of NF-kappaB to the nucleus; CCl4 induced NF-kappaB DNA binding activity was blocked by curcumin treatment. These findings suggest that curcumin prevents acute liver damage by at least two mechanisms: acting as an antioxidant and by inhibiting NF-kappaB activation and thus production of proinflammatory cytokines.
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PMID:Curcumin protects against acute liver damage in the rat by inhibiting NF-kappaB, proinflammatory cytokines production and oxidative stress. 1738 25

Alcohol abuse is a major cause of liver cirrhosis as well as chronic liver disease. The aim of the present study was to investigate the possible correlation, between liver dysfunction biological markers and vitamin B12, with interleukin-6, in the serum of alcohol-dependent individuals without liver disease (AWLD). In a sample of 43 alcohol abusing/dependent subjects (33 males and 10 females) treated on an inpatient basis according to a standard detoxification protocol, the serum activities of the hepatic enzymes (ASAT, ALAT, gamma-GT), as well as the concentration of B12 and IL-6, were determined on admission. A strong positive correlation has been observed between IL-6 and B12, ASAT, ALAT, and gamma-GT at the beginning of the detoxification period. The results confirmed that in alcohol-dependent individuals, the median serum concentration of IL-6, before the beginning of the treatment, had a significant positive correlation with the liver dysfunction biological markers and B12. In conclusion, IL-6 might be used as an additional diagnostic marker for the degree of liver dysfunction in alcohol dependent individuals.
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PMID:Vitamin B12 and hepatic enzyme serum levels correlate with interleukin-6 in alcohol-dependent individuals without liver disease. 1744 94

Thioacetamide (TAA) has been used extensively in the development of animal models of acute liver injury. Frequently, TAA is administered intraperitoneally to induce liver damage under anaesthesia. However, it is rarely administered by intravenous injection in conscious rats. The experiments in this study were designed to induce acute liver damage by single intravenous injection of TAA (0, 70 and 280 mg/kg) in unrestrained rats. Biochemical parameters and cytokines measured during the 60-h period following TAA administration, included white blood cells (WBC), haemoglobulin (Hb), platelet, aspartate transferase (GOT), alanine transferase (GPT), total bilirubin (TBIL), direct bilirubin (DBI), albumin, ammonia (NH3), r-glutamyl transpeptidase (r-GT), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Rats were sacrificed by decapitation 60 h after TAA administration and livers were removed immediately for pathology and immunohistochemical (IHC) examination. Another group of rats were sacrificed by decapitation 1, 6 and 24 h after TAA administration and livers were removed immediately for time course change of pathology and IHC examination. TAA significantly increased blood WBC, GOT, GPT, TBIL, DBIL, NH3, r-GT, TNF-alpha and IL-6 levels but decreased the blood Hb, platelet and albumin level. The levels of histopathological damage in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 60 h after TAA administration. The levels of inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB (NF-kappaB) detected by IHC in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 1 h after TAA administration. Single intravenous TAA administration without anaesthesia is a restorable animal model which may be used to investigate acute liver damage.
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PMID:Single dose intravenous thioacetamide administration as a model of acute liver damage in rats. 1842 1

The major clinical challenge for cancer therapy remains the eradication or prevention of metastatic process. This study was an investigation of the antimetastatic activity of Biophytum sensitivum, using B16F-10 melanoma-induced experimental lung metastasis in C57BL/6 mice. B. sensitivum treatment significantly reduced lung tumor nodule formation accompanied by reduced lung collagen hydroxyproline, hexosamine, and uronic acid levels. Serum sialic acid and gamma-glutamyl transpeptidase levels were also significantly inhibited after B. sensitivum treatment. B. sensitivum treatment down-regulated the expression of matrix metalloprotease-2 and -9 and at the same time upregulated the lung tissue inhibitor of metalloprotease-1 and -2 expression. The cytokine profile and growth factors such as interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, granulocyte monocyte-colony stimulating factor, vascular endothelial growth factor, interleukin-2 and tissue inhibitor of metalloprotease-1 in the serum of these animals were markedly altered after B. sensitivum treatment. This altered level of cytokines after B. sensitivum treatment was also accompanied by enhanced natural killer cell and antibody-dependent cellular cytotoxicity. The study reveals that B. sensitivum treatment could alter proinflammatory cytokine production and could inhibit the activation and nuclear translocation of p65, p50, c-Rel subunits of nuclear factor-kappaB, and other transcription factors such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element-binding protein in B16F-10 melanoma cells.
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PMID:Anti-metastatic effect of Biophytum sensitivum is exerted through its cytokine and immunomodulatory activity and its regulatory effect on the activation and nuclear translocation of transcription factors in B16F-10 melanoma cells. 1847 42

Increased serum resistin was found in rodent models of obesity and insulin resistance, whereas contradictory results have been obtained in human studies. In humans, resistin is primarily released by monocytes/macrophages, suggesting that soluble levels may be associated with macrophage activation. Here, systemic and monocyte-released resistin levels were found to be similar in type 2 diabetic (T2D) patients, overweight controls and normal-weight controls. When adjusted for body mass index and age, serum resistin modestly correlated with gamma-glutamyltransferase levels, fasting glucose and interleukin-6. Systemic resistin was marginally increased in T2D patients treated with beta-blockers or urate-lowering drugs and was considerably higher in patients treated with loop diuretics. Monocyte-released resistin was even reduced by the loop diuretic furosemide, excluding the possibility that this drug may directly stimulate resistin synthesis. In summary, the current data indicate that changes accompanying renal dysfunction but not obesity or type 2 diabetes are associated with increased serum resistin.
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PMID:Systemic resistin is increased in type 2 diabetic patients treated with loop diuretics. 2181 94


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