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)

Evidence from epidemiological and histopathologic studies in humans with autoimmune type 1 (insulin-dependent) diabetes suggests that beta-cell destruction within the islets of Langerhans progresses through a number of stages. In this review we draw on recent experimental evidence in an attempt to define the molecular pathology of these stages. Stage 1 is postulated to be initiated by modification of the beta cell by virus, chemical or other factors, leading to the production of interferon-alpha, hyperexpression of major histocompatibility complex (MHC) class I molecules and induction of MHC class II molecules. Experiments in transgenic mice suggest that overexpression of MHC molecules is in itself detrimental to beta-cell function. Shedding of antigen(s) from dying beta cells in combination with hyperexpression of MHC molecules may be a powerful immunogenic stimulus. Stage 2 commences with infiltration of the islets by immuno-inflammatory cells (termed insulitis). It is proposed that production of cytokines from the infiltrating cells induces "phenotypic switching" in beta cells, with further upregulation of MHC molecules and the induction of intracellular adhesion molecule-1 expression and interleukin-6 production. Together, these properties are seen as a prerequisite for the presentation of autoantigen by beta cells to adherent T lymphocytes and autoimmune activation. The final stage encompasses autoimmune-mediated destruction of the beta cells by the targeted delivery of cytotoxic cytokines and other mediators.
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PMID:Molecular pathology of type 1 diabetes. 223 44

An autograft of skeletal muscle on rat dorsal medulla is a permanent opening in the blood-brain barrier to solutes. Is the graft also a site for the entry of exogenous, isogeneic leukocytes? Five weeks after inserting the graft, peritoneal macrophages (M phi) from inbred Fischer rats were activated by phorbol myristate acetate, labeled with a fluorescent dye, and infused as a bolus of about 2 x 10(6) cells into the axillary artery of Fischer hosts. The cells circulated for 2 h. The brains were then fixed, frozen, and sectioned. Only when M phi had been activated and a muscle autograft inserted did appreciable numbers of M phi enter the medulla. Nonactivated M phi invaded the grafts but very few entered the brain at 2 h. In rats with gel foam grafts, only a few activated M phi invaded gel and brain. Before entering tissues, M phi must adhere to the lumenal face of vessels. Cell adhesion molecules, e.g., I-CAM-1 and its ligand adhesion molecule, leukocyte function antigen (LFA-1), are known to mediate adhesion. I-CAM-1, detected immunohistochemically, increased in graft vessels and in nearby brain vessels. The rise may have been mediated by cytokines, interleukin-6, and tumor necrosis factor-beta, found in the grafts. LFA-1, however, assayed by fluorescence-activated cell sorting, was on both activated and nonactivated, exogenous M phi. Thus, M phi-endothelial attachment may have involved other adhesion molecules, e.g., selectins. The autograft also induced major histocompatibility complex class I on microglia and classes I and II on brain vessels near the graft. These vessels, by expressing adhesion molecules, are entry routes into brain for activated, isogeneic leukocytes that can then migrate for a limited distance of 1-2 mm in an otherwise intact brain.
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PMID:Brain vessels near muscle autografts are sites for entry of isogeneic macrophages into brain. 750 59

Endothelial monolayers were prepared from neonatal heart or liver tissue of Lewis (Le) rats. Cells in their first passage of culture were used to investigate the short-term (1 hr at 37 degrees) binding of 51Cr-labelled Le rat lymphocytes prepared from the mesenteric lymph node (MLN), peripheral lymph node (PLN) or Peyer's patches (PP) to those endothelia, or the activation by concanavalin A (Con A) or irradiated (Lewis x Brown Norway)F1 (LBNF1), of Le cells on the monolayers after 84 hr in culture. MLN and PP showed preferential binding to, and activation on, liver endothelium compared with heart endothelium (approximately twofold difference), while the converse was seen with PLN. No inhibition of binding was seen with antibodies to intracellular adhesion molecule-1 (ICAM-1) or lymphocyte function-associated antigen-1 (LFA-1). Preincubation of endothelial cells with plasma isolated from the portal or hepatic vein of normal adult mice (5% plasma, 37 degrees for 14 hr) caused a 1.5-2-fold stimulation of binding of MLN/PP to heart endothelium, which was inhibited (> or = 75%) by anti-ICAM-1 or anti-LFA-1, and a fourfold stimulation of binding to liver endothelium, which was not inhibited by these monoclonal antibodies (< or = 25% inhibition). In contrast, antibodies to tumour necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6) caused inhibition of activation of liver endothelium (> or = 75%), while producing little affect on activation of heart endothelium. Similar results were seen when lymphocyte activation on endothelial cells rather than adhesion cells was investigated. Our data suggest a heterogeneity in lymphocyte-endothelial interactions, which is further regulated, under physiological conditions, by the liver.
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PMID:Hepatic regulation of lymphocyte adhesion to, and activation on, syngeneic endothelial monolayers. 782 67

The production of interleukin-6, intracellular adhesion molecule 1, and major histocompatibility complex class II molecules by a renal carcinoma cell line (ACHN) in response to S fimbriae of uropathogenic Escherichia coli was studied. S fimbriae adhered to ACHN cells and stimulated the production of interleukin-6 and intercellular adhesion molecule 1 but did not affect major histocompatibility complex class II expression by renal carcinoma cells. Our data demonstrate that S fimbriae of E. coli display immunomodulating properties on kidney-derived epithelial cells.
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PMID:Differential expression of interleukin-6, intracellular adhesion molecule 1, and major histocompatibility complex class II molecules in renal carcinoma cells stimulated with S fimbriae of uropathogenic Escherichia coli. 809 98

Myocardial dysfunction following prolonged ischemia and reperfusion is at least partially dependent upon adhesion of neutrophils to myocardial and endothelial cells. Neutrophils are thought to contribute to reperfusion injury by two mechanisms: impairment of the microvasculature by physical obstruction, and secretion of products that damage microvasculature and myocardium. Cytokines have been shown to play several roles in neutrophil aggregation. Interleukin-6 (IL-6), along with IL-1 and tumor necrosis factor-alpha (TNF-alpha), induces the expression of intracellular adhesion molecule-1 (ICAM-1) in myocytes and endothelial cells, respectively. These cytokines also inhibit contractility and nitric oxide release (a vasodilator), and IL-1 and TNF-alpha have been found to reduce adrenergic stimulation of myocardial contractility by reducing intracellular cyclic AMP levels and uncoupling adenylate cyclase from beta receptors. The transforming growth factors, TGF-alpha and TGF-beta, also have a role in reperfusion injury. TGF-alpha reduces endothelial cell release of nitric oxide, while TGF-beta appears to protect against reperfusion injury by reducing plasma TGF-alpha levels, blocking neutrophil adherence, and promoting nitric oxide release. Although cytokines are likely to have important roles in reperfusion injury, their involvement in myocardial stunning is unclear.
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PMID:Cytokines and reperfusion injury. 846 22

In cardiac operations endopeptidase (protease) inhibitor may be beneficial in reducing myocardial injury when administered in the cardiopulmonary bypass prime. Nafamostat mesilate was evaluated in 20 patients who underwent coronary artery bypass grafting. The patients were divided into a control group (n = 10) and a nafamostat group (n = 10). Nafamostat (2 mg/kg per hour) was continuously given during cardiopulmonary bypass in the nafamostat group. The age, number of grafts, cardiopulmonary bypass time, and aortic crossclamp time were similar between groups. In the control group, neither tumor necrosis factor-alpha nor interleukin-1 levels showed any significant change during cardiopulmonary bypass, whereas interleukin-6 and interleukin-8 levels, percent expression of adhesion molecule (CD18) on neutrophils, and CH50 assay results increased significantly during cardiopulmonary bypass. As compared with the control group, the nafamostat group showed significantly lower levels of interleukin-6 (123 +/- 57 versus 40 +/- 22 pg/ml, respectively) and interleukin-8 (96 +/- 13 versus 66 +/- 14 pg/ml, respectively). The nafamostat group showed a significantly lower difference of CH50 assay results and malondialdehyde levels between coronary sinus blood and arterial blood and peak values of creatine kinase MB (43 +/- 12 IU/L versus 19 +/- 6 IU/L) during the postoperative course compared with findings in the control group. These results demonstrated that inflammatory reactions induced by cardiopulmonary bypass had adverse effects on myocardial recovery after aortic crossclamping and that nafamostat mesilate given during cardiopulmonary bypass appeared to reduce myocardial reperfusion injury by attenuating such inflammatory reactions. Attenuation of inflammatory reactions of cardiopulmonary bypass should be considered in the strategy of myocardial protection.
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PMID:Attenuation of cardiopulmonary bypass-derived inflammatory reactions reduces myocardial reperfusion injury in cardiac operations. 855 86

Respiratory syncytial virus (RSV), the most common etiologic agent of epidemic pediatric respiratory disease, infects and replicates in the human airway epithelium, resulting in the induction of cellular gene products essential for immune and inflammatory responses. We describe the effect of RSV infection on nuclear factor-IL6 (NF-IL6) expression, a human basic domain-leucine zipper-containing transcription factor that alone in combination with other inducible transcription factors regulates the expression of cytokine and adhesion molecule genes. RSV-infected human type II pulmonary alveolar epithelial cells (A549) synthesize a single 45.7-kDa isoform of NF-IL6 rapidly and in a time-dependent manner. NF-IL6 is first detectable after 3 h of infection and continues to accumulate until 48 h (until the cells lose viability). NF-IL6 production could not be induced by UV-inactivated virus, demonstrating the requirement of viral replication for NF-IL6 synthesis. Immunoprecipitation after [35S]methionine metabolic labeling was done to investigate the mechanism for NF-IL6 production. There was robust NF-IL6 protein synthesis within RSV-infected (24 h) cells. Protein synthesis occurred without detectable changes in the abundance or size of the single 1.8-kb NF-IL6 mRNA. RNase protection assay of transfected chloramphenicol acetyltransferase reporter genes driven by either wild-type or mutated NF-IL6 binding sites show a virus-induced increase in NF-IL6-dependent transcription. These studies have demonstrated a novel inducible mechanism for translational control of NF-IL6 synthesis and identify this transcription factor as a potential effector of the host response to RSV infection.
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PMID:Inducible translational regulation of the NF-IL6 transcription factor by respiratory syncytial virus infection in pulmonary epithelial cells. 862 74

Concentrations of prostaglandin E2, interleukin-6, and interleukin-8 were determined in the hip joint synovial fluid of 20 patients undergoing primary (n = 12) and revision (n = 8) total hip arthroplasties. Levels of soluble adhesion molecules were also investigated in these patients. There was a significant and marked increase in levels of prostaglandin E2 (P < .001), interleukin-6 (P < .011), interleukin-8 (P < .0002), soluble intercellular adhesion molecule 1 (P < .07), soluble vascular adhesion molecule 1 (P < .0006), and soluble endothelial leukocyte adhesion molecule 1 (P < .0003) in joint fluid of patients undergoing revision. On the basis of these observations, it is suggested that synovial fluid and its inflammatory contents could play a significant role in the pathogenesis of aseptic loosening in total hip arthroplasties.
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PMID:Role of inflammatory mediators and adhesion molecules in the pathogenesis of aseptic loosening in total hip arthroplasties. 874 66

Once thought as immunologically naive, cells from the central nervous system have been shown to become immunologically reactive and produce various substances including cytokines and adhesion molecules. Recent investigations have revealed that mRNAs of certain cytokines such as tumor necrosis factor, interleukin-1, and interleukin-6 are expressed in the ischemic brain of the animals. Chemokines including CINC, MCP-1, and MIP-1, as well as adhesion molecules such as ICAM-1. ELAM and P-selectin were also found to be expressed. Although identification of the cells producing these cytokines were often difficult, neurons, endothelia, activated astrocytes and microglia/macrophages were the likely sources. The induction of these molecules in ischemic brain is time-locked and appears to be controlled in a highly regulated manner during the process of ischemic cascade. The functional role, interrelationship, and basic mechanism of action of these molecules are being increasingly recognized, while trials such as antiadhesion antibody molecules, growth factors, and anticytokine antibodies have been successful in reducing the neuronal damage in animals subjected to ischemic injury. Furthermore, changes of certain cytokines or adhesion molecules have been detected in the serum or cerebrospinal fluid of patients with stroke and related diseases suggesting that these molecules play a role in the pathogenesis of human stroke. Understanding of these cytokine-adhesion molecule cascades in the ischemic brain may allow us to develop new strategies for the treatment of stroke.
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PMID:Cytokines and adhesion molecules in stroke and related diseases. 878 58

Although the pathogenesis of the acute respiratory distress syndrome (ARDS) is complex and poorly understood, several observations point to an important role of interactions between polymorphonuclear neutrophils (PMN) and cytokines in this process. We therefore studied certain parameters involved in PMN transendothelial migration (adhesion molecule expression and cytoskeletal organization) in patients with ARDS (n = 14) in comparison with other ventilated patients (n = 15). We found that in the basal state, both whole-blood PMN and alveolar PMN obtained by bronchoalveolar lavage (BAL) were activated, as shown by decreased L-selectin CD62L and increased beta 2 integrin CD11b expression, as well as decreased F-actin content. The degree of PMN activation increased with the degree of lung injury and with the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8). Moreover, the capacity of ex vivo stimulation of alveolar PMN by a bacterial peptide was low in ARDS and could partly account for the high susceptibility of these patients to lung infection. Therefore, ARDS-associated lung injury could be caused, at least in part, by inappropriate adhesion and transendothelial migration of proinflammatory cytokine-primed PMN.
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PMID:Interactions between neutrophils and cytokines in blood and alveolar spaces during ARDS. 881 May 92


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