UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytokines belong to the group of main factors regulating of leukaemia cell proliferation. Most of information comprised in the literature concern the behaviour of single cytokines in the cell culture in vitro. In the organism of leukaemia patient many different cytokines, adhesion molecules, growth factors and other substances probably act in the same time. Therefore the aim of study was the determination of plasma concentrations of interleukin 1B, 3, 4, 6, 8, G-CSF and P-selection in 26 patients with acute myeloblastic leukaemia-aml, among them 14 patient in the course of exacerbation-aml-e and 12 being in the remission-aml-r, classified as type M1 and M2 according to the FAB classification. Control group consisted of 15 healthy volunteers. The cytokine measurements were performed by means of immunoradiometric, immunoenzymatic and radioimmunologic kits. In the patients with aml-e significant increase of plasma concentrations of IL-1B, IL-3, IL-6, G-CSF, P-selectin and essential decrease of IL-4 was found. Significant decrease of IL-4 and P-selecting concentrations in the patients with aml-r and lack of changes in IL-8 concentrations in the both groups of patients was demonstrated. The observed differences of concentrations may additionally confirm the role of studied cytokines and P-selectin in the regulation of leukaemia cell proliferation.
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PMID:[Cytokines in acute myeloid leukemia]. 982 57

Neutrophils, or polymorphonuclear leukocytes (PMNLs), migrate through vascular endothelium and in connective tissue during inflammation. In rats with adjuvant arthritis, migration to joints of radiolabeled (111In) blood PMNLs was examined to define the role of specific selectin and integrin adhesion molecules in this process. Based on monoclonal antibody studies, P-selectin was required for normal PMNL migration to the joints. Although E-selectin alone was not essential, it mediated PMNL accumulation when the P-selectin mechanism was blocked. However, 30% to 40% of the PMNL accumulation was L-, P-, and E-selectin-independent. The integrins, LFA-1 and Mac-1 (CD11/CD18), and VLA-4 mediated PMNL migration to arthritic joints. However, 20% to 40% of PMNL accumulation was via CD18- and VLA-4-independent mechanisms. Human PMNL migration in vitro across unstimulated human umbilical vein endothelial cells (HUVEC), induced by C5a or IL-8, was virtually all mediated by the CD18 (beta2) integrins, LFA-1 and Mac-1. PMNL transendothelial migration was partly CD18-independent (35%) when endothelium was activated with cytokines, such as interleukin-1, and a chemotactic gradient, such as C5a, was also present. This CD18-independent migration was partially E-selectin-dependent in vitro. PMNL migration across synovial fibroblasts induced by C5a was mediated by Mac-1, VLA-4, VLA-5, and VLA-6, functioning in concert. However, up to 30% of migration was via mechanisms as yet to be defined. Thus, PMNL transendothelial and extravascular migration involves some shared, and some distinct mechanisms, as well as some yet to be identified. Defining these mechanisms may help develop therapies for controlling PMNL involvement in inflammation in the vascular and extravascular spaces.
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PMID:Adhesion molecules mediating neutrophil migration to arthritis in vivo and across endothelium and connective tissue barriers in vitro. 983 14

Isoprostanes are metabolites of arachidonic acid found in blood under various conditions of oxidative stress. Because arachidonic acid derivatives are major mediators of inflammation, we investigated the potential inflammatory effects of iPF2alpha-III (previously 8-isoPGF2alpha) and iPE2-III (8-isoPGE2) on human polymorphonuclear granulocytes (PMN), as well as on human umbilical vein endothelial cells (HUVECs). The early activation marker CD11b on PMN and the adhesion molecules ICAM-1, E-selectin, and P-selectin on HUVECs were quantified by flow cytometry. Levels of the cytokines interleukin (IL)-6 and IL-8 were measured in the culture supernatant by enzyme-linked immunosorbent assay. Furthermore, adhesion of PMN to HUVECs was assessed. Neither isoprostane showed any direct stimulatory effects on PMN or HUVECs at concentrations of 0.1 or 1 microM: there was no acute elevation in expression of CD11b or P-selectin and no change of ICAM-1 or E-selectin after 4 or 24 h of incubation, respectively. The levels of interleukin IL-6 and IL-8 were also unaltered. However, PMN adhesion was significantly enhanced both after 4 and 24 h of incubation of HUVECs with iPF2alpha-III, and CD11b expression on PMN was elevated by contact of these cells with the supernatant of pre-exposed HUVECs. Neither of these actions were inhibited by an endothelin receptor antagonist (bosentan) or a combined thromboxane A2/isoprostane-receptor antagonist (SQ29548). Thus, although not having a direct pro-inflammatory potential, isoprostanes might indirectly accentuate PMN stimulation. This seems to occur via a receptor-independent mechanism, perhaps the production of an active metabolite of isoprostanes by endothelial cells.
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PMID:Indirect enhancement of neutrophil activity and adhesion to cultured human umbilical vein endothelial cells by isoprostanes (iPF2alpha-III and iPE2-III). 1048 Apr 86

Soluble recombinant (r) P-selectin and rP-selectin immobilized on plastic surfaces were tested for their capacity to activate neutrophils to produce superoxide anion. Soluble rP-selectin was incapable of activating leukocytes, whereas immobilized rP-selectin was able to induce leukocyte activation. When neutrophils were pretreated with a low dose of IL-8, granulocyte colony stimulating factor or granulocyte macrophage colony stimulating factor, soluble rP-selectin was no longer inert. These cytokine-primed leukocytes produced superoxide anion in the presence of soluble rP-selectin. During this priming period, sialyl Lewis X (sLe(X)) epitopes redistributed to one end of the leukocytes. Similar polarization of sLe(X) epitopes was observed at the attachment site of cells that adhered to immobilized rP-selectin. Cap formation and superoxide anion production induced by solid-phase P-selectin or by IL-8 and soluble rP-selectin treatment were inhibited by treatment of the leukocytes with cytochalasin B. These observations suggest that the redistribution of the carbohydrate ligands and the polarization of the leukocyte surface through an active process is a prerequisite but not sufficient to leukocyte superoxide production through P-selectin.
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PMID:Redistribution of selectin counter-ligands induced by cytokines. 1074 50

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
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PMID:Endothelial function and hemostasis. 1079 71

The application of hyperthermia (HT) and tumour necrosis factor alpha (TNF) in isolation perfusion of the limb or liver results in regression of advanced cancers confined to these regions of the body in most patients and are thought to exert anti-tumour effects primarily on tumour neovasculature. However, the individual contribution of either treatment factor on endothelial cells (EC) are not known. In this study, we investigated the in vitro effects of moderate and severe HT on human umbilical vein EC (HUVEC) with and without TNF in clinically relevant doses. HUVEC were exposed to normothermia (37 degrees C) or moderate (39 degrees C) and severe (41 degrees C) HT for 90 or 180 min with or without TNF (1 microg/ml). Cell viability, cytokine secretion (IL-6, IL-8, VEGF, ICAM-1, VCAM-1, RANTES, E-selectin, P-selectin, L-selectin, and PECAM-1), and induction of procoagulant activity as reflected in tissue factor (TF) production were assessed at the end of the treatment period and at several time points thereafter. Neither HT nor TNF exerted significant cytotoxic effects on EC at the doses and temperatures used. HT resulted in increased production of PECAM-1 with little or no additional effect when combined with TNF. TNF caused increased secretion of IL-6, IL-8, ICAM-1, and VCAM-1 with little or no additional effect from HT. Increased E-selectin and RANTES levels were observed with TNF and HT only at 24 h after treatment. HT and TNF had mainly antagonistic effects on VEGF secretion with HT causing primarily decreased production and TNF causing increased VEGF secretion under all temperatures. Most notably, there was a rapid, prolonged and synergistic peak increase in procoagulant activity when TNF and HT were used in combination compared to TNF or HT treatment alone. These results indicate that TNF and HT exert primarily independent effects on inflammatory cytokine production in EC but synergistically increase procoagulant activity as reflected in TF production. These data provide a possible mechanism for the thrombotic effects in tumour neovasculature seen following isolation perfusion with these agents and provide a rationale for their combined use in this treatment setting.
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PMID:Effects of hyperthermia and tumour necrosis factor on inflammatory cytokine secretion and procoagulant activity in endothelial cells. 1080 14

Cardiopulmonary bypass (CPB) is known to induce an inflammatory response in association with neutrophil mediated lung injury. P-Selectin has been reported to be involved in the initiation of this inflammatory response by promoting the adhesion of neutrophils to endothelial cells in postcapillary venules. However, the role of P-selectin in the inflammatory response induced by CPB has never been clarified. To elucidate its role, we evaluated the effect of an anti-rat specific P-selectin monoclonal antibody (ARP2-4; Sumitomo Pharmaceutical) on the response of inflammatory cytokines and lung injury in a rat-CPB model. Twenty Sprague-Dawley rats underwent CPB for 30 minutes (80 ml/kg per minute, 34 degrees C) under one of two conditions. In group P, ARP2-4 (3 mg/kg) was added to the priming solution of the bypass circuit (n = 10). Saline alone was given to group C (n = 10). Inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin[IL]-1beta, IL-6, and IL-8) and respiratory index (RI) as a marker of pulmonary gas-exchange ability were measured 1) before the initiation of CPB, 2) at the termination of CPB, and 3) 2 hours after the termination of CPB. Neither TNF-alpha nor IL-1beta was detected during the experimental period in either group. The plasma levels of IL-6 and IL-8 increased after CPB in both groups, but they were significantly lower in group P than in group C. The RI value increased in a pattern similar to that of the inflammatory cytokines and was significantly lower in group P. These data demonstrate that the addition of an anti-rat specific monoclonal antibody inhibits the abnormal release of inflammatory cytokines and attenuates CPB induced lung injury in rats. Thus, P-selectin may play a role in the augmentation of CPB induced inflammatory response, and the use of its inhibitory monoclonal antibody seems to be a promising strategy for the treatment of CPB induced lung injury.
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PMID:P-selectin monoclonal antibody may attenuate the whole body inflammatory response induced by cardiopulmonary bypass. 1082 47

Although neutrophil migration from the systemic circulation involves the beta2- (or CD18) integrin family, the existence of an alternative, CD18-independent route of neutrophil extravasation to tissues has been demonstrated in animal models. The molecular interactions involved in this alternative migratory route have not yet been characterized. The objective of this study was to assess the CD18-dependency of neutrophil migration across human endothelial cells from an organ known to support CD18-independent migration, the lung, with a view to establishing an in vitro model to facilitate study of CD18-independent migration. Neutrophil migration across human pulmonary artery endothelial cells (HPAECs) in response to three different chemoattractants, formylmethionyl leucylphenyl-alanine (FMLP), interleukin (IL)-8, and leukotriene (LT) B(4), was examined. Results demonstrated that a function-blocking antibody to CD18 decreased FMLP-stimulated migration by 71.7 +/- 4.4% (P < 0.001). In contrast, migration in response to LTB(4) was decreased by only 20.5 +/- 10.2% (P < 0.01), and no significant decrease was observed with migration to IL-8. Neutrophils that migrated to FMLP had 1.7-fold more surface CD11b/CD18 compared with nonmigrated neutrophils (P < 0.01), whereas this integrin complex was not significantly upregulated on neutrophils that had migrated to IL-8 or LTB(4). Further investigation of this migratory route indicated that it did not involve the beta1 integrins (CD29) or the endothelial selectins, E- or P-selectin, nor did it require the activity of either metalloproteinases or neutrophil elastase. These results indicate that neutrophil migration across HPAECs in vitro to IL-8 and LTB(4) is predominantly CD18-independent and provides a much-needed in vitro system for examination of the neutrophil-endothelial interactions involved in this alternative migratory route.
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PMID:Interleukin-8 and leukotriene-B(4), but not formylmethionyl leucylphenylalanine, stimulate CD18-independent migration of neutrophils across human pulmonary endothelial cells in vitro. 1091 80

The expression of adhesion molecules on vascular endothelial cells determines the pattern of migration and extravasation of leucocytes in inflammation and immunity. Here we show that costimulation with CD40 ligand (CD40L) and interleukin (IL)-4 (or IL-13) gives rise to a unique pattern of adhesion molecule expression by human umbilical vein endothelial cells (HUVEC). CD40 ligation alone enhanced expression of vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and E-selectin whereas IL-4 and IL-13 increased expression of VCAM-1 and P-selectin but not ICAM-1 or E-selectin. When IL-4 and CD40L were combined there was an additional increase of both VCAM-1 and P-selectin, but ICAM-1 and E-selectin were both inhibited. The combined effects of IL-4 and CD40L signalling were not the result of altered response kinetics, enhanced sensitivity of the endothelium, or increased expression of CD40 or the IL-4 receptor. The rise in VCAM-1 expression induced by combined IL-4 and CD40L stimulation was slower and more sustained than with tumour necrosis factor-alpha (TNF-alpha) and occurred only on a subset (75-80%) of the endothelial cell population compared to 100% with TNF-alpha. Costimulation with IL-4 and CD40L increased adhesion of T cells and B cells above levels obtained with either signal alone, but decreased adhesion of neutrophils. Furthermore, CD40 and IL-4 synergistically increased IL-6 but decreased IL-8 production by HUVEC. These results show that interactions between IL-4 and CD40 on endothelial cells give rise to specific patterns of adhesion molecule expression and cytokine production that may have important implications for lymphocyte and neutrophil migration and function at sites of inflammation.
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PMID:Biological function of CD40 on human endothelial cells: costimulation with CD40 ligand and interleukin-4 selectively induces expression of vascular cell adhesion molecule-1 and P-selectin resulting in preferential adhesion of lymphocytes. 1092 70

Levels of platelet-derived microparticles (PMPs), platelet activation markers (P-selectin expressed on, or annexin V binding to, platelets (plt:P-selectin or plt:annexin V, respectively)), chemokines (IL-8, monocyte chemotactic peptide-1 (MCP-1), and regulated on activation normally T-cell expressed and secreted (RANTES)), and soluble P- and E-selectins were compared in peripheral blood from diabetic and control patients in order to develop a better understanding of their potential contribution to diabetic vascular complications. Significant increases were found for PMPs, plt:P-selectin, MCP-1, RANTES and soluble P- and E-selectins in diabetic individuals, whereas IL-8 levels were similar. Furthermore, after ticlopidine treatment, most of these factors receded to baseline levels observed in non-diabetic patients. Our findings indicate that ticlopidine might be able to prevent or reduce vascular complications in diabetic patients.
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PMID:Significance of chemokines and activated platelets in patients with diabetes. 1097 8

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