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)

Thrombosis and inflammation are closely related. However, the response of the vein wall to venous thrombosis has been poorly documented. This study examines the hypothesis that venous thrombosis is associated with an inflammatory response in the vein wall. In a rat model of inferior vena caval thrombosis, vein wall was temporally examined for inflammation by assessment of histopathology, leukocyte morphometrics, and cytokine levels. Animals were killed 1 hour and 1, 3, and 6 days after thrombus induction. Our findings demonstrated an early (day 1) neutrophil infiltration into the vein wall followed by a later (days 3 and 6) monocyte/macrophage and lymphocyte response. Cytokines were elevated only under conditions of venous thrombosis. Levels of epithelial neutrophil activating protein-78 (ENA-78), tumor necrosis factor-alpha (TNF), interleukin-6, and JE/monocyte chemoattractant protein-1 (JE/MCP-1) increased over the 6-day period, while macrophage inflammatory protein-1 alpha (MIP-1 alpha) peaked at day 3 after thrombus induction. Additionally, rats were passively immunized with neutralizing antibodies to TNF, ENA-78, MIP-1 alpha, JE/MCP-1, intercellular adhesion molecule-1 (ICAM-1), and CD18 compared with control antibodies. The most effective antibody early after thrombus induction for attenuating vein wall neutrophil extravasation was anti-TNF (P < .01). The monocyte/macrophage extravasation was inhibited most by anti-ICAM-1 followed by anti-TNF (P < .01). These findings demonstrate that venous thrombosis is associated with significant vein wall inflammation that is partially inhibited by neutralizing antibodies to cytokines and adhesion molecules.
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PMID:Venous thrombosis-associated inflammation and attenuation with neutralizing antibodies to cytokines and adhesion molecules. 774 35

Infiltration of leukocytes and mononuclear cells into the glomeruli is an early pathological finding in human and experimental glomerulonephritis. However, the cellular and molecular basis for cell infiltration into the glomeruli is not yet completely understood. In addition, there is little information on the expression of intercellular adhesion molecule-1 (ICAM-1) on glomerular cells. In the present study, we investigated the expression of ICAM-1 on cultured bovine glomerular endothelial cells (GEN) and its regulation by the pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and lipopolysaccharide (LPS). Immunocytochemical staining showed that ICAM-1 molecules were constitutively expressed on the surface of GEN. In flow cytometric and ELISA analyses, ICAM-1 molecule expression on GEN was significantly upregulated by IL-1 beta, MCP-1 and LPS in a dose-dependent manner, but not by IL-6. LPS was the most potent inducer of ICAM-1 molecule expression on GEN. The effects of IL-1 beta, MCP-1 and LPS were observed as early as 4 h and reached a maximal level by 18 h. These results suggest that ICAM-1 on GEN can participate in the infiltration of mononuclear cells into glomeruli in human and experimental glomerulonephritis.
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PMID:Expression of intercellular adhesion molecule-1 on cultured glomerular endothelial cells by pro-inflammatory cytokines and lipopolysaccharide. 775

Cytokines are now considered as constitutive factors of the brain. Some of them are involved in the mechanism regulating lineage commitment and cellular differentiation of the central nervous system (CNS). We describe here the analysis of gene expression in cortex and hippocampus, of interleukin-1 alpha (IL1), interleukin-2 (IL2), interleukin-6 (IL6), macrophage-colony stimulating factor-1 (MCSF) and monocyte chemoattractant protein-1 (MCP1) in fetal (day 18 of gestation; G18), newborn (postnatal day 2; P2), young (postnatal day 21; P21) and adult rat using the reverse transcriptase-polymerase chain reaction (RT-PCR). IL6 and MCP1 mRNA presented distinct patterns of expression levels: IL6 mRNA level is most highly expressed in the embryonic cortex, whereas MCP1 is expressed at a maximal level in the postnatal day 2 cortical area. In the hippocampus, IL6 is most expressed at the adult stage and MCP1 exhibits an equal level of expression from day two to the adult stage. However, under our experimental conditions, IL1 alpha, IL2 and MCSF mRNA were not observed. Thus, certain cytokine genes, each with a specific pattern, are expressed in the rat CNS in adult and during ontogenesis. These observations suggest that cytokines might be involved as regulating factors promoting CNS development.
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PMID:Developmental expression of cytokine genes in the cortex and hippocampus of the rat central nervous system. 780 81

Cytokine generation by tissue-infiltrating mononuclear cells (TIMC) and by keratinocytes (KC) was investigated in material obtained from the oral mucosal tissues of patients with oral lichen planus (OLP). Peripheral blood mononuclear cells (PBMC) and chronically inflamed and noninflamed gingival KC (CIG-KC, NOR-KC, respectively) were used as the controls. Compared to NOR-KC and CIG-KC, KC from OLP patients (OLP-KC) produced much more interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The OLP-KC superiority in the production of these cytokines was more prominent when the KC were cultured in the presence of interleukin-1 beta (IL-1 beta), lipopolysaccharide and phorbol myristate acetate. OLP-KC also produced more monocyte-chemotactic factor(s) which were not inactivated by the antibodies against GM-CSF, macrophage colony-stimulating factor and monocyte chemoattractant protein-1. TIMC in OLP tissues (OLP-TIMC) were superior to PBMC in the generation of IL-6 and GM-CSF. OLP-TIMC were stimulated to produce more TNF-alpha by IL-1 beta, IL-6 and GM-CSF, more IL-6 by IL-1 beta and GM-CSF, and more GM-CSF by IL-1 beta and IL-6 than PBMC. When compared to cytokine generation in TIMC from the chronically inflamed gingivae, more interferon-gamma, IL-6 and TNF-alpha were generated by OLP-TIMC. These results indicate that KC play a critical role in OLP, producing cytokines including monocyte-chemotactic factor(s), and that the cytokines produced by TIMC and OLP-KC through autocrine and paracrine processes enhance the local inflammatory response.
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PMID:Cytokine production by keratinocytes and mononuclear infiltrates in oral lichen planus. 796 86

Vascular access dysfunction is an important cause of morbidity for dialysis patients and a major contributor to hemodialysis cost. Thrombosis is a leading cause of vascular access failure, and usually results from stenotic lesions in the venous outflow system. This study was designed to explore the impact of serum levels of various risk factors for thrombosis and accelerated fibrointimal hyperplasia on progressive stenosis, and the subsequent thrombosis of hemodialysis fistula. A cross-sectional and 2-yr prospective pilot study was performed in 30 nondiabetic hemodialysis patients with primary arteriovenous fistula. Venous dialysis pressure, urea recirculation, color Doppler sonography, and angiography were used to monitor vascular access patency. Eleven patients (37%) developed a progressive stenosis in the venous circuit, which was complicated by thrombosis in three patients. Compared with the patients without fistula dysfunction, these patients had higher serum levels of monocyte chemoattractant protein-1 and interleukin-6, two cytokines that regulate the proliferation of vascular smooth muscle cells, which is the key mechanism in the pathogenesis of fistula stenosis. In addition, they had hyperinsulinemia, hyperlipidemia, and increased plasma levels of two hemostasis-derived risk factors for thrombosis: plasminogen activator inhibitor type 1 and factor VII. Monocyte chemoattractant protein-1, interleukin-6, plasminogen activator inhibitor type 1, factor VII, triglycerides, and the ratios for cholesterol/HDL-cholesterol, apolipoprotein (apo) A-I/ apo C-III, apo A-I/apo B, and glucose/insulin were independent predictors of fistula dysfunction. This study demonstrates the influece of cytokines, hemostasis-derived vascular risk factor, hyperinsullnemia, and abnormallties of lipids and apolipoproteins on primary fistula survival. The assessment of these factors might be useful for the identification of the patients at risk of fistula stenosis and thrombosis.
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PMID:Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients. 886 9

Recent clinical and experimental evidence indicates that many of the sequelae of hemolytic transfusion reactions may be mediated by cytokines, including interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, the chemokines interleukin-8 and monocyte chemoattractant protein-1, and interleukin-1 receptor antagonist. Experimental models of both acute and delayed hemolytic transfusion reactions demonstrate the production of these molecules. The time course and relative patterns of production correlate well with known clinical manifestations of these reactions. Tumor necrosis factor-alpha appears to be central to ABO incompatibility reactions, and stimulates endothelial cells to exhibit procoagulant activity and surface adhesion molecules.
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PMID:Cytokines as intercellular signals in hemolytic transfusion reactions. 889 Dec

Osteocytes are differentiated forms of osteoblasts that arise upon entrapment within the bone matrix. In this report, we describe the establishment and hormonal regulation of the first conditionally transformed human preosteocytic cell line. Primary adult bone cells were obtained from protease cell line. Primary adult bone cells were obtained from protease digestion of cancellous chips. The cells were infected with adenovirus-ori- SV40 tsA 209, which encodes for a temperature-sensitive large T-antigen. After immortalization, we isolated a clone designated HOB-01-C1. This cell line expressed the mutant T-antigen and proliferated at the permissive temperature (34 C) but stopped dividing at the nonpermissive temperature (39-40 C). Electron microscopy of cells incubated at 39 C demonstrated the presence of preosteocytic cellular processes, some of which appeared to form gap junctions or were rich in microfilaments. The clone expressed alpha 1 type (I) procollagen messenger RNA (mRNA) and secreted type I procollagen C peptide at both temperatures, and this expression was elevated 1.6-fold to 1.8-fold at 40 degrees C. The cells expressed very low basal levels of alkaline phosphatase activity (approximately 0.02 nmol/min.mg), which was increased 2- to 5-fold in a dose-dependent manner by 0.1-100 nM 1 alpha,25-dihydroxyvitamin D3 (vitamin D3) at both temperatures. Vitamin D3 also increased osteocalcin secretion in a dose-dependent manner when the clone was maintained at 34 C (approximately 6-fold), and this stimulation was enhanced > 5 fold at 40 C. In contrast to the low expression of alkaline phosphatase, the cells secreted high amounts of osteocalcin in response to vitamin D3 (approximately 15 ng/mg cell protein); this biochemical profile also resembled that of preosteocytes. Alizarin red-S histochemical staining demonstrated that these cells rapidly produced mineralized nodules at both temperatures. PTH (10 and 100 nM) had no effect on the intracellular accumulation of cAMP at 34 C but stimulated a 14- to 18-fold increase in the production of this second messenger at 40 C. In contrast, 100 nM prostaglandin E2 and 1 microM forskolin stimulated cAMP synthesis better at 34 C. Western blot analysis indicated that the cells expressed CD44, a putative osteocytic marker, at both temperatures. Finally, interleukin-1 beta and tumor necrosis factor-alpha (1-1000 pM) stimulated dose-dependent increases in the secretion of interleukin-6 and monocyte chemoattractant protein-1 at 34 C and 40C. We conclude that the HOB-01-C1 cell line has a preosteocytic phenotype. Moreover, these cells respond to calcitropic hormones and bone resorbing cytokines.
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PMID:Establishment and hormonal regulation of a conditionally transformed preosteocytic cell line from adult human bone. 889 22

The normal intestinal immune system is under a balance in which proinflammatory and anti-inflammatory cells and molecules are carefully regulated to promote a normal host mucosal defense capability without destruction of intestinal tissue. Once this careful regulatory balance is disturbed, nonspecific stimulation and activation can lead to increased amounts of potent destructive immunologica and inflammatory molecules being produced and released. The concept of balance and regulation of normal mucosal immune and inflammatory events is indicative of how close the intestine is to developing severe inflammation. The normal intestinal mucosal immune system is constantly stimulated by lumenal contents and bacteria. The stimulatory molecules present in the intestinal lumen that activate and induce subsequent mucosal immunologic and inflammatory events include bacterial cell wall products, such as peptidoglycans and lipopolysaccharides, as well as other chemotactic and toxic bacterial products that are produced by the many different types of bacteria within the gastrointestinal tract. These highly stimulatory bacterial cell wall products are capable of activating macrophages and T lymphocytes to release potent proinflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). IL-1, IL-6, and TNF-alpha increase the presence of human leukocyte antigen (HLA) class II antigen-presenting molecules on the surfaces of epithelial cells, endothelial cells, macrophages, and B cells, thus increasing their ability to present lumenal antigens and bacterial products. The proinflammatory cytokines IL-1 and TNF-alpha also increase the ability of epithelial cells, endothelial cells, macrophages, and fibroblasts to secrete potent chemotactic cytokines, such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), which serve to increase the movement of macrophages and granulocytes from the circulation into the inflamed mucosa. Thus, through lumenal exposure to potent, nonspecific stimulatory bacterial products, the state of activation of the intestinal immune system and mucosal inflammatory pathways are markedly up-regulated. This raises the question of whether there is a deficiency in effective down-regulation through the absence of normally suppressive cytokines such as interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), interleukin-4 (IL-4), and IL-1 receptor antagonist. Normally, the turning off of the active and destructive immunologic and inflammatory events should occur following the resolution of a bacterial or viral infection that has been appropriately defended against and controlled by the mucosal immune system. In inflammatory bowel disease (IBD), however, the down-regulatory events and processes that should turn off the immunologic and inflammatory protective processes, once the pathogenic agent has been cleared, appear to be deficient or only partially effective. We may find that we ultimately are dealing with disease processes that have more than one genetic or cellular basis. The improved understanding of the immunopathophysiology of IBD will allow exploration of novel immunologic and genetic approaches, such as gene replacement therapy, administration of a suppressor cytokine or an altered cell surface antigen, the administration of humanized monoclonal antibodies directed against proinflammatory cytokines, or the development of newer strategies against fundamental cell biologic mechanisms such as adhesion molecules.
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PMID:Alterations of the mucosal immune system in inflammatory bowel disease. 902 61

In order to examine the specificity of cytokine production during coronary artery bypass graft (CABG) surgery, we serially measured serum levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF), in twenty patients between 52 and 80 years of age, during surgery and 2 days afterwards. Serum MCP-1, as well as IL-8 and IL-6, increased significantly during the surgery (P < 0.05), while IL-1 beta and TNF did not. MCP-1, IL-8 and IL-6 concentrations were not different in the sera of three patients tested at three different sites, i.e., the hepatic vein, pulmonary artery and radial artery. They increased in parallel in each patient, although the actual timing of the increase relative to the surgical step varied among individuals. In complicated patients, MCP-1, IL-8 and IL-6 showed higher peaks and persisted longer than in patients without complications. The universal and simultaneous appearance of MCP-1, IL-8 and IL-6 could indicate that these three cytokines may be stimulated by a yet undiscovered stimulus (or stimuli) which occurs systemically despite the independent pathways of production.
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PMID:Transient rise in serum cytokines during coronary artery bypass graft surgery. 911 Jan 50

The strong resemblance between the clinical manifestations of hemolytic transfusion reactions and sepsis, in which cytokine production has a central role, suggests that similar pathophysiologic mechanisms are involved. There is an expanding body of clinical and experimental evidence that cytokines, especially interleukin-1, tumor necrosis factor, interleukin-6, and interleukin-8, are principle mediators of immune responses to erythrocyte incompatibility. Recent studies have further suggested that the monocyte chemotactic and activating factor, monocyte chemoattractant protein-1, and the anti-inflammatory cytokine interleukin-1 receptor antagonist are produced in experimental models of hemolytic transfusion reactions. Differing levels and patterns of expression of these cytokines may be seen in models of intravascular hemolysis due to ABO incompatibility and extravascular hemolysis due to Rh incompatibility, which correlate with the recognized clinical differences between these two types of reactions. Furthermore, recent studies have demonstrated that several of these same cytokines are produced during the storage of platelet concentrates, which may account for some febrile reactions that are not prevented by the use of leukocyte reduction filters.
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PMID:Cytokines and erythrocyte incompatibility. 937 22


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