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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression and function of gonadotropin receptors, and the secretion of steroids, transferrin, and cytokines were investigated in three immortalized (single transfection with v-myc) mouse granulosa cell lines (GRM01, GRM01L, and GRM02). A dose-dependent increase in progesterone production was obtained in GRM01 and GRM02 cells after addition of LH, FSH, modulators of the adenylate cyclase enzyme system, and cAMP analogues. The LH-induced release of progesterone was already detectable in GRM02 cells after 8 h and was related to incubation time and cell number. Both epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) induced the secretion of progesterone in GRM02 cells, while no effect was obtained with TGF beta. LH receptor concentration was highest in the GRM02 cell line. FSH receptor mRNA was visualized in GRM01 and GRM02 cells. Aromatase activity in GRM02 cells was induced by androgens and inhibited by aromatase inhibitors. Whereas all cell lines were able to secrete transferrin, only in GRM01 cells was transferrin secretion increased significantly by LH. FSH did not affect transferrin secretion in the three cell lines, in contrast to forskolin or 8-bromo-cAMP. The immortalized mouse granulosa cell lines were able to express and release several growth factors. The expression and secretion of activin, inhibin, TGF beta, EGF, TGF alpha, insulin-like growth factor II, fibroblast growth factor (acidic and basic), platelet-derived growth factor, and interleukin-6 suggest an autocrine or paracrine role for these factors in follicular differentiation and function. In conclusion, these cells, derived from mural granulosa cells and immortalized in a preovulatory state, can be used to study granulosa cell physiology or to study the role of granulosa cells and their derivatives in the process of follicular maturation, fertilization, and early embryonic development.
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PMID:Secretion of steroids, growth factors, and cytokines by immortalized mouse granulosa cell lines. 802 76

The simian immunodeficiency virus SIVsmmPBj14 (SIV-PBj14) is an atypical lentivirus that causes acute disease and death in pig-tailed macaques and in vitro replicates efficiently in resting macaque lymphocytes and activates and induces proliferation of lymphocytes. The present study was conducted to test the hypothesis that production of large quantities of SIV-PBj14 induces widespread immune activation and elaboration of cytokines which lead directly to the death of infected pig-tailed macaques. Following intravenous inoculation of pig-tailed macaques with SIV-PBj14, acute disease developed and was characterized by high levels of plasma viremia, p27gag antigenemia, tumor necrosis factor alpha, and interleukin-6 (IL-6). All animals died within 10 days of infection, at which time some animals had as many as 100% CD4+ cells in the periphery and lymphoid tissues infected. During the last few days before death, titers of infectious virus in blood increased as much as 10(5)-fold. By using dual-label immunofluorescence assays for detection of cell surface activation markers, both CD4+ and CD8+ lymphocytes were shown to express the IL-2 and transferrin receptors following either in vivo or in vitro infection with SIV-PBj14. Furthermore, in vitro infection of quiescent macaque lymphocytes by SIV-PBj14 was accompanied by proliferation of both CD4+ and CD8+ lymphocyte subsets, as measured by incorporation of [3H]thymidine. Increases in numbers of activated lymphocytes and levels of proinflammatory cytokines in plasma coincided with increased amounts of detectable virus in vivo. Clinical signs of disease and pathologic findings were most consistent with death from a shock-like syndrome, in which acute-phase inflammatory cytokines are known to play a major role. Tumor necrosis factor alpha, IL-2, and IL-6 were detected in some cultures infected with SIV-PBj14, but this finding was not consistent. When cytokines were detected, their concentrations were essentially no different from those found in control cultures infected with SIVsmm9, a prototypic strain from which SIV-PBj14 was derived. The in vivo results suggest a synergistic cycle of activation of lymphocytes and monocytes, elaboration of cytokines, and virus production that accelerates uncontrolled and culminates in death. The observed correlations between in vivo and in vitro activation events following SIV-PBj14 infection validate the use of in vitro studies to clarify lentivirus-lymphocyte interactions that may contribute to the virulence of SIV-PBj14.
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PMID:Immune activation and viral burden in acute disease induced by simian immunodeficiency virus SIVsmmPBj14: correlation between in vitro and in vivo events. 805 36

Intestinal blood loss as well as chronic inflammation are regarded as the most important mechanisms in the pathogenesis of anemia in Crohn's disease. In addition, cytokines such as interleukin-6 can suppress erythropoietin production. This study was performed to investigate the importance of iron status, inflammatory activity, and endogenous erythropoietin concentrations for the development of anemia in Crohn's disease. In 49 consecutive patients with Crohn's disease, hemoglobin, inflammatory activity (Crohn's disease activity index, C-reactive protein, alpha 1-acid glycoprotein), iron status (serum iron, transferrin, transferrin saturation, ferritin), and serum erythropoietin levels were studied. Anemic (Hb < 12.0 g/dl; N = 16) vs nonanemic patients (Hb > or = 12 g/dl; N = 33) showed reduced iron compartments (eg, ferritin 28.7 +/- 12.9 micrograms/liter vs 63.2 +/- 15.0 micrograms/liter, transferrin saturation 6.2 +/- 1.4% vs 11.5 +/- 1.3%, P < 0.01) but no differences in inflammatory activity. An inverse correlation between erythropoietin and hemoglobin concentrations was found (r = -0.62; P < 0.001), but the increase in erythropoietin levels was inadequate to the degree of anemia. There was no correlation between erythropoietin and interleukin-6 serum levels. Four of five anemic patients with hemoglobin below 10.5 g/dl and erythropoietin levels within the normal range were treated with parenteral iron (200 mg iron saccharate in 250 ml NaCl, weekly, intravenously). Two of them additionally received recombinant human erythropoietin (150 units/kg, 3x weekly, subcutaneously). After five weeks all patients had a marked increase in hemoglobin. However, the mean increase in erythropoietin-treated patients was 5.0 g/dl compared to 2.0 g/dl in the patients with iron therapy only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anemia in Crohn's disease. Importance of inadequate erythropoietin production and iron deficiency. 808 99

Human thymic epithelial cells (TEC) of medullary phenotype were cultured for 14 days in a growth factor-defined serum-free medium. The effects of added growth factors on cell numbers and the production of cytokines were investigated by separate exclusion of the various growth factors from the medium. We found that hydrocortisone stimulated cell proliferation but inhibited the differentiation of TEC and significantly reduced the production of interleukin-1 alpha, interleukin-6 and granulocyte-macrophage colony stimulating factor. Insulin was found to enhance the differentiation of TEC and the production of the three cytokines. Transferrin and choleratoxin were found to inhibit cell proliferation, but they did not affect production of the cytokines. Exclusion of epidermal growth factor, however, leads to cell death. We conclude that it is essential to exclude hydrocortisone from the medium to optimize production of cytokines, and that transferrin and choleratoxin seem to be unnecessary constituents in serum-free cultures of human TEC.
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PMID:Effects of growth factors on cytokine production in serum-free cultures of human thymic epithelial cells. 835 99

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)
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PMID:Regulation of iron metabolism in HepG2 cells: a possible role for cytokines in the hepatic deposition of iron. 840 63

Our study addressed the role of the human hepatocyte growth factor (HGF), a potent mitogen for mature rat and human hepatocytes, in the regulation of specific hepatic genes. The experimental evidence obtained in primary cultured human hepatocytes indicates that HGF regulates the synthesis of plasma proteins in a dose-response fashion. It stimulates the synthesis of the negative acute-phase proteins albumin, transferrin, and fibronectin, decreases that of alpha1-antichymotrypsin (ACT) and haptoglobin, and stimulates that of alpha2-macroglobulin (AMG), which in man is insensitive to inflammatory mediators. HGF had no effect on C-reactive protein (CRP) synthesis. These effects differ from those elicited by interleukin-6 (IL-6). The effects of HGF on fibrinogen and alpha1-antitrypsin were, however, similar to those induced by IL-6. The effects of HGF were also observed at the messenger RNA (mRNA) level. Time-course induction experiments showed that the effects of HGF on protein synthesis were delayed by about 48 to 72 hours, in contrast with the 12-hour lag found after IL-6 stimulation. Although the presence of glucocorticoids was not absolutely necessary for HGF to affect plasma protein synthesis, it moderately extended the effects. In pulse-chase experiments, it was found that the action of HGF was not due to an alteration of the rate of secretion of the proteins. The effects of HGF on the synthesis of albumin, transferrin, fibronectin, alpha1-antichymotrypsin, and haptoglobin could be counteracted by the simultaneous presence of IL-6 in the incubation media. A clear additive effect was observed only in the case of fibrinogen. No interaction was observed in the cases of CRP and AMG. The results of this study indicate that the effects of HGF on human hepatocytes may not simply be limited to its mitogenic activity, but that it also regulates hepatic-specific genes and antagonizes, in part, the action of IL-6.
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PMID:The hepatocyte growth factor regulates the synthesis of acute-phase proteins in human hepatocytes: divergent effect on interleukin-6-stimulated genes. 867 50

In 115 women (healthy controls and patients with benign and malignant gynaecological tumors) interleukin-6 was determined in blood plasma with the aim to decide whether elevated IL-6 levels may be used as a marker of ovarian carcinoma. In spite of statistically significantly increased IL-6 levels the authors do not regard at present the IL-6 values as a useful marker of ovarian carcinoma for two reasons: first, until now it is not decided whether elevated IL-6 values originate only from the cells of epithelial ovarian carcinoma or if they are also produced by tumour-associated macrophages or both and second: in a large number of cases (both controls and patients with malignant tumors) no IL-6 levels in blood plasma could be detected. For these reasons it seems to be more convenient (even economically) to determine in suspected cases and after exclusion of any inflammatory process the levels of prealbumin and transferrin. Significantly decreased levels of both have a high value of primary sensitivity (66% and 87% resp.).
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PMID:[Interleukin-6 and acute phase reactants in the diagnosis of ovarian carcinoma]. 896 93

To investigate the influence of functioning on unexplained senile anemia, we measured commonly used hematological parameters (serum iron, transferrin, iron saturation and ferritin) in addition to specific erythropoietic factors, such as interleukin-3 (IL-3), interleukin-6 (IL-6), and erythropoietin (EPO) in 48 elderly subjects aged 65-90 years. The subjects were divided into 3 groups: 1) 17 patients with unexplained mild anemia; 2) 17 non-anemic patients with newly acquired stroke and who previously were functionally active; 3) 14 functionally active patients with no major disease who served as controls. Anemia was defined as hemoglobin (Hb) values under 12.0 g/dL. The degree of functional ability was defined and scored by the "functional independence measure" (FIM) test. Data are presented as mean values +/- SD. The results revealed a correlation between the functional state and levels of Hb, iron and transferrin with unchanged iron saturation. Patients in the mild anemia group were found to be functionally declined (FIM = 57 +/- 19.4) with the relatively lowest mean iron (75.1 +/- 17 micrograms/dL) and transferrin levels (243 +/- 42.6 micrograms/dL). The stroke group (FIM = 62 +/- 17.7) had intermediate levels of iron (85.4 +/- 20.3 micrograms/dL) and transferrin (245 +/- 45.2), and with the continuation of the declined functional state the Hb level decreased significantly (13.7 +/- 0.9 to 12.0 +/- 1.0 g/dL, p < 0.001). The highest mean values of iron (102 +/- 27.9 micrograms/dL) and transferrin (322 +/- 42.7 micrograms/dL) were found in the control group (FIM = 122.7 +/- 5.8). The ferritin levels showed an opposite trend. IL-3 values were undetectable in the anemic and control groups, and were elevated in some patients in the stroke group. The lowest IL-6 level was observed in the anemic group, and the highest in the control group. Serial IL-6 assays in the stroke group showed an upward trend. Erythropoietin levels in all groups showed no difference.
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PMID:Relationship between routine hematological parameters, serum IL-3, IL-6 and erythropoietin and mild anemia and degree of function in the elderly. 958 49

It has been proposed that cytokines mediate the acceleration of bone loss following menopause. Because of the intimate relationship between bone marrow stromal cells and bone tissue, it is possible that marrow cells and their products contribute to the bone microenvironment and influence the regulation of bone cell differentiation and activity. We examined the production of cytokines by bone marrow stromal cells from a total of 37 women and 15 men undergoing total hip replacement for noninflammatory joint disease. Low-density mononuclear cells were isolated from bone marrow and were cultured in phenol red-free alpha MEM medium supplemented with 10% FBS and antibiotics. Constitutive secretion of interleukin-6 (IL-6) was positively correlated with age in a series of 8 women and 5 men measured by bioassay (r = 0.98; P < 0.01) and in a series of 18 women and 10 men measured by immunoassay (r = 0.56; P < 0.01). The pattern of cytokine production by bone marrow stromal cells was examined in detail in 23 postmenopausal women, aged 49-88 yr. Basal secretion of immunoreactive IL-6 and IL-11, but not granulocyte-macrophage colony-stimulating factor, increased with time in culture. Exogenous IL-1 beta stimulated secretion of IL-6 and IL-11 in a saturable, dose-dependent manner. Secretion of soluble IL-6 receptor was not correlated with secretion of IL-6, either constitutively or in the presence of IL-1 beta. In 4 of 14 samples, IL-1 beta also stimulated secretion of granulocyte-macrophage colony-stimulating factor. IL-1 beta was undetectable in 7 of 9 cultures during the 2-week culture period. IL-6 did not stimulate secretion of IL-1 beta in the 7 cultures tested. Cells were dependent upon serum for viability and growth and were not sustained by a serum substitute (1% insulin-transferrin-selenium-BSA). Cells grown in medium with 10% FBS and supplemented with 1% insulin-transferrin-selenium-BSA secreted 10-fold more IL-6 than cells grown in serum alone. Marrow from 7 women receiving estrogen replacement therapy showed lower constitutive secretion of IL-6 (75%; P < 0.006) and IL-11 (43%; P < 0.05) than marrow from age-matched controls and had blunted stimulation of IL-6 and IL-11 secretion by exogenous IL-1 beta. These data indicate distinct patterns of cytokine production by human marrow stromal cultures dependent upon age and estrogen status.
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PMID:In vitro secretion of cytokines by human bone marrow: effects of age and estrogen status. 962 37

The aim of this study was to evaluate the potential advantages of perioperative versus postoperative administration of an enteral immune-enhancing diet on host defense and protein metabolism. Thirty subjects, candidates for gastrectomy for cancer, were randomly allocated into two groups. The first group (n = 15) received an enteral formula enriched with arginine, omega-3 fatty acids, and RNA 7 d before and 7 d after surgery; the second group (n = 15) received the same diet but only 7 d after surgery. Postoperative immune and inflammatory responses were investigated by phagocytosis ability of polymorphonuclear cells, interleukin-2 receptors (IL-2R), lymphocyte subsets, interleukin-6 (IL-6), and delayed hypersensitivity response (DHR). Prealbumin (PA), retinol binding protein, albumin, and transferrin were determined as protein synthesis indicators. Perioperative immunonutrition prevented the early postoperative impairment of phagocytosis, DHR, total number of lymphocytes, and CD4/CD8 ratio (P < 0.05 versus postoperative group). The IL-2R levels were significantly higher in the perioperative group (P < 0.05 versus postoperative on postoperative day [POD] 4 and 8). Perioperative group also showed lower levels of IL-6 (P < 0.05 versus postoperative on POD 1, 4, and 8) and higher levels of PA (P = 0.04 versus postoperative on POD 8). The perioperative administration of immunonutrition ameliorated the host defense mechanisms, controlled the inflammatory response, and improved the synthesis of short half-life constitutive proteins.
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PMID:Immunonutrition in gastric cancer surgical patients. 983 29


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