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)

Human B cells capable of spontaneous IgG secretion are commonly found in circulation and in lymphoid tissues such as tonsil and bone marrow (BM). The present study compares the mechanisms that regulate tonsil, blood and BM B cells capable of spontaneous IgG secretion. The BM cell subset produced IgG during a markedly longer period of time (14 days) than did tonsil and blood cell subsets (2-3 days). Blood and BM, but not tonsil, B cell IgG secretion depended on the presence of adherent cells, as demonstrated by adherent cell depletion and re-addition experiments. Stromal BM cells supported linear IgG secretion by non-adherent BM cells for 2 weeks, but were unable to prolong the short-term IgG secretion by tonsil and blood cells. Different factors induced IgG secretion in each of the three B cell populations as optimal IgG secretion by tonsil, blood or BM cell subsets required either tumor necrosis factor-alpha, interleukin-6 or fibronectin + interleukin-6, respectively. Finally, these populations also showed differences in the expression of adhesion molecules; the tonsilar cell subset was PNA+/- CD44+ CD49d+ CD49e- Leu-8+/-, the blood cell subset was PNA- CD44+/- CD49d+ CD49e- Leu-8+ and the BM cell subset was PNA- CD44+/- CD49d+ CD49e- Leu-8-. These results suggest that the mechanisms controlling the final differentiation and the expression of adhesion molecules in these B lymphocytes exhibit territorial specificity.
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PMID:Human tonsil, blood and bone marrow in vivo-induced B cells capable of spontaneous and high-rate immunoglobulin secretion in vitro: differences in the requirements for factors and for adherent and bone marrow stromal cells, as well as distinctive adhesion molecule expression. 829 84

The immunopharmacological activities of a fungal (1-->3)-beta-D-glucan, OL-2, isolated from "Leiwan" Omphalia lapidescens were examined. Intraperitoneal (i.p.) administration of OL-2 to ICR mice induced a significant number of peritoneal exudate cells (PEC) and white blood cells over the period of a few days. Spleen cell numbers were also increased by i.p. administration of OL-2 at about a week. These changes reverted to the normal level within a month. Responses of spleen cells and bone marrow cells (BM) to colony stimulating factors (CSF) were augmented by OL-2 administration assessed by cell proliferation assay. Sera from OL-2 administered mice contained an increased concentration of colony stimulating activity. Gene expressions of interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha in the spleen were also increased. These results suggested the activation of hematopoietic responses, and would well relate to the incremental increase in PEC, white blood cell and spleen cell numbers. OL-2 also increased the serum concentration of fibronectin and complement component C-3. However, OL-2 did not show adjuvant activity to SRBC and antitumor activity against the solid form of Sarcoma 180 by i.p. administration. Yet, OL-2 did not interfere with the antitumor activity of SSG against the same tumor system. These facts suggested that OL-2 could enhance nonspecific host defense mechanisms by enhancing hematopoietic responses, but would not enhance or inhibit the specific immunity mediated by lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunopharmacological characterization of a highly branched fungal (1-->3)-beta-D-glucan, OL-2, isolated from Omphalia lapidescens. 835 93

Neurological complications are a major cause of morbidity and mortality in patients with disseminated malignant melanoma. We have studied and correlated clinical and cerebrospinal fluid (CSF) findings in 20 patients with central nervous system metastases from malignant melanoma including 8 patients with metastatic meningeal melanomatosis (MMM) and 12 patients with solid cerebral metastases (SCM). The putative CSF tumor markers, fibronectin and beta 2-microglobulin, were elevated significantly in MMM but not in SCM patients. A prominent increase in the IgM index, which reflects intrathecal B-cell stimulation, and a rise of IgG index, interleukin-6, and tumor necrosis factor-alpha in MMM patients provide preliminary evidence for a local intrathecal immune response triggered by melanoma cell invasion of the subarachnoid space.
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PMID:Intrathecal IgM response in disseminated cerebrospinal metastasis from malignant melanoma. 841 Jan 43

The pathophysiology of vaso-occlusive crisis in sickle cell disease involves interactions among blood cells, plasma proteins, and vessel wall components. The initial goal of this work was to quantify the adhesion of sickle red blood cells (RBCs) to fibronectin immobilized on glass under both static and dynamic shear stress conditions. High-power microscopic inspection of static assay plates showed striking numbers of adherent neutrophils as well as RBCs. Sickle neutrophils and RBCs were significantly more adherent to fibronectin than the corresponding normal cells in static adhesion assays. Adhesion of both sickle neutrophils and sickle RBCs in dynamic adhesion assays was promoted by a period of static incubation preceding initiation of shear stress conditions. Adherent neutrophils remained attached at shear stresses up to 51 dyne/cm2; most adherent RBCs were attached at shear stresses up to 13 dyne/cm2, but detached at a shear stress of 20 dyne/cm2. Sickle neutrophil adhesion was enhanced significantly by autologous plasma. Elevated levels of plasma interleukin-6 (IL-6; but not IL-1 or IL-8) were found in 6 of 9 sickle cell disease samples examined, and elevated levels of tumor necrosis factor were found in 2 of 9 samples. Plasma IL-6 levels correlated positively with both the number of sickle neutrophils adherent to fibronectin and the ability of sickle plasma to enhance adhesion of normal neutrophils to fibronectin. These data suggest possible roles for neutrophil activation and for fibronectin in mediating sickle neutrophil and RBC adhesion.
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PMID:Adhesion of sickle neutrophils and erythrocytes to fibronectin. 855 2

A mesothelioma cell line, termed T-85, was established from a patient with malignant peritoneal mesothelioma and remarkable thrombocytosis (1.4 x 10(6)/mm3). Electron microscopically, two types of mesothelioma cells have been characterized; the major type of cells with dense-cored granules in the cytoplasm and the minor one with evenly dense granules. Immunologically, the cells showed staining for interleukin-6 (IL-6), cytokeratin, collagen type IV, vimentin, laminin, fibronectin and Factor VIII-related antigen. Quantitation by ELISA revealed a high concentration of IL-6 in T-85 cell culture supernatants. RT-polymerase chain reaction of T-85 cells showed two positive bands of cDNA at 628 and 251 base pairs indicating the constitutive expression of IL-6 and IL-6 receptor mRNA. Moreover, prominent pro-platelet process formation activity in T-85 cell culture supernatants indicated the presence of a thrombopoietic activity due mainly to IL-6 but not the c-Mpl ligand or erythropoietin. However, the fact that 15% of PPF activity remained in the supernatants treated with anti-IL-6 antibody indicated the presence of another thrombopoietic substance. T-85 is so far the first mesothelioma cell line derived from a case with remarkable thrombocytosis.
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PMID:Establishment and characterization of a new human mesothelioma cell line (T-85) from malignant peritoneal mesothelioma with remarkable thrombocytosis. 887 1

After acute lung injury, altered bronchioloalveolar epithelia must be repaired quickly in order to restore lung function. During reepithelialization, type II cells initially appear to migrate and spread over a remodeled matrix; then a secondary proliferative phase occurs. It was hypothesized that 1) type II cells can develop locomotion in vitro that is modulated by growth factors, proinflammatory cytokines, and substrate adhesion molecules and 2) migration and proliferation of type II cells can occur as distinctive processes. Chemotaxis assays were elaborated using short term cultures of rat type II pneumocytes. Epidermal growth factor (EGF), transforming growth factor-alpha, laminin, fibronectin were found to be the main attractants for type II cells with respective increases of approximately 8.5-, 10.5-, 8-, and 7-fold in cell migration (P<0.05 vs. control). Laminin induced gradient-dependent and random cell migration. Addition of laminin with EGF had a synergistic effect in promoting cell migration (approximately 30-fold increase over control, P<0.05). Interferon-gamma and interleukin-6 inhibited EGF-induced type II cell migration, whereas tumor necrosis factor-alpha and interleukin-1beta acted as primers for type II cell migration (approximately 1.5-fold increase over control, P<0.05. Type II cells did not need to be in a proliferative phase in order to exhibit motility. New insights regarding the regulatory processes for type II cell migration are especially relevant in our understanding of early events occurring during epithelial repair after acute lung injury.
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PMID:Lung alveolar epithelial cell migration in vitro: modulators and regulation processes. 863 22

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

The effects of a third-generation bisphosphonate, YM175 (disodium dihydrogen (cycloheptylamino)-methylene-1,1-bisphosphonate), on bone resorption induced by a metastatic human melanoma cell line (A375) were investigated morphologically using an experimental model of bone metastases in nude mice. An injection of A375 in the left cardiac ventricle produced multiple osteolytic lesions. Then, 4 weeks after the cell injection, we administrated YM175 (1 mg/kg) intravenously once and sacrificed the animals 3 days later. On histochemical observation, there was a layer of stromal cells with numerous mononuclear and multinucleated tartrate-resistant acid phosphatase (TRAPase)-positive cells in the untreated control group. In contrast, this layer was extensively reduced in most areas, and only a few TRAPase-positive cells were seen around tumor nests and on the bone surface in the experimental group. Most of the TRAPase-positive cells were stained only weakly and/or homogeneously, and there was little evidence of cell polarity. Some of them were vacuolated. Ultrastructurally, they were round and devoid of ruffled borders and clear zones. The findings suggest that YM175 decreases the number and activity of osteoclasts. In addition, a few showed the morphology of cell death, which seemed to be one of the reasons leading to the decrease of osteoclasts. There was no substantial change in the morphological relationships or ultrastructure of osteoclast precursor cells, stromal cells, extracellular matrices, and tumor cells between the experimental and the control groups. In the experimental group, the distribution of extracellular matrices (heparan sulfate proteoglycan and fibronectin) was less conspicuous, but the localization of osteotropic cytokines (interleukin-6 and prostaglandin E2) was essentially similar to that of the control group. The cause leading to the decrease of osteoclast precursor cells remains to be clarified. In conclusion, YM175 inhibits bone resorption induced by tumor, by decreasing the activity of mature osteoclasts and possibly affecting the production of osteoclast precursor cells.
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PMID:Inhibitory effects of bisphosphonate (YM175) on bone resorption induced by a metastatic bone tumor. 871 29

The purpose of this study is to measure soluble CD14 (sCD14) levels in sera from newborn with sepsis, to compare it with other markers, and to study its evolution in Gram-negative and Gram-positive sepsis. Forty normal newborns were included (26 were full term and 14 were preterm infants), 20 babies had a positive blood culture (11 Gram-positive and 9 Gram-negative) and 16 cases were suspected of having sepsis based on clinical and laboratory findings, but a negative blood culture. Interleukin-6 (IL-6), sCD14, and tumour necrosis factor-alpha (TNF alpha) were measured by enzyme immunoassay, and fibronectin (FN) and C-reactive protein (CRP) by radial immunodiffusion. Neonates with a positive blood culture had increased levels of sCD14 (3.20 +/- 1.26 micrograms ml-1, p < 0.001), CRP (69 +/- 46 micrograms ml-1, p < 0.001) and IL-6 (134 +/- 150 pg ml-1, p < 0.001), and decreased values of FN (12.3 +/- 6.6 mg ml-1, p < 0.001). TNF alpha levels were also high (160 +/- 37 pg ml-1), but this increase was not statistically significant. Newborn infants suspected of having sepsis but a negative blood culture had similar but milder abnormalities. Soluble CD14 levels correlated with CRP values; however, there was no correlation between sCD14, TNF alpha and IL-6. Neonates with sepsis by Gram-positive bacteria had lower sCD14 levels than patients with Gram-negative sepsis (2.63 +/- 1.2 versus 4.04 +/- 1.0 micrograms ml-1, p < 0.05). In conclusion, the sCD14 level is increased in newborn infants with sepsis, and this is higher in infections by Gram-negative bacteria, suggesting a different contribution of monocyte and macrophage cells. In contrast, IL-6, TNF alpha, CRP and FN values are similar in infections by Gram-positive and Gram-negative bacteria.
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PMID:Serum levels of CD14 in neonatal sepsis by Gram-positive and Gram-negative bacteria. 881 13

Contact of various cells with extracellular matrix molecules modulates their cellular functions and phenotype. Most investigations have employed dishes coated with purified matrix constituents or plain collagen I lattices omitting the effects of other important matrix components such as proteoglycans. In this study we analyze the effect of purified glycosaminoglycans (GAGs) on human fibroblasts and human umbilical vein endothelial cells (HUVEC) embedded within collagen I/III lattices. HUVEC contracted collagen I/III gels far less efficiently than fibroblasts and addition of heparan sulfate and heparin almost completely inhibited contraction. In collagen gels HUVEC down-regulated collagenase mRNA while increasing collagen I, IV mRNA expression. Addition of heparin and heparan sulfate reversed the collagen IV mRNA induction whereas hyaluronic acid and chondroitin sulfate enhanced fibronectin and collagenase transcripts. Fibroblasts readily contracted collagen gels, and mRNA levels for fibronectin, collagenase and interleukin-6 were stimulated. Gel contraction was mostly unaffected by the different glycosaminoglycans. Fibroblasts responded to the addition of dermatan sulfate, heparan sulfate and heparin with a decrease in fibronectin, collagenase and interleukin-6 mRNA. Binding studies revealed saturable binding sites on fibroblasts and HUVEC for 35S-labelled heparin, demonstrating specificity for heparin and heparan sulfate over other GAGs in competition experiments. This study implies that glycosaminoglycans participate in cell-matrix interactions by effectively modulating the cellular phenotype via high affinity binding sites.
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PMID:Glycosaminoglycans modulate cell-matrix interactions of human fibroblasts and endothelial cells in vitro. 883 71


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