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)

Brief episodes of ischemia can render an organ resistant to subsequent severe ischemia. This 'ischemic preconditioning' is ascribed to various mechanisms, including oxidative stress. We investigated whether preconditioning exists on an endothelial level. Human umbilical vein endothelial cells (HUVECs) were transiently confronted with oxidative stress (1 mM H(2)O(2), 5 min). Adhesion molecules ICAM-1 and E-selectin and release of cytokines IL-6 and IL-8 to subsequent stimulation with TNF-alpha (2.5 ng/ml, 4 h) were measured (flow cytometry and immunoassay), as were nuclear translocation of the transcription factor NFkappaB (Western blotting, confocal microscopy) and redox status of HUVECs (quantification of glutathione by HPLC). TNF-alpha elevated IL-6 in the cell supernatant from 8.8 +/- 1 to 41 +/- 3 pg/ml and IL-8 from 0.5 +/- 0. 03 to 3 +/- 0.2 ng/ml. ICAM-1 was increased threefold and E-selectin rose eightfold. Oxidative stress (decrease of glutathione by 50%) reduced post-TNF-alpha levels of IL-6 to 14 +/- 3 and IL-8 to 1 +/- 0.2; the rise of ICAM-1 was completely blocked and E-selectin was only doubled. The anti-inflammatory effects of preconditioning via oxidative stress were paralleled by reduction of the translocation of NFkappaB on stimulation with TNF-alpha, and antagonized by the intracellular radical scavenger N-acetylcysteine. 'Anti-inflammatory preconditioning' of endothelial cells by oxidative stress may account for the inhibitory effects of preconditioning on leukocyte adhesion in vivo.
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PMID:Endothelial preconditioning by transient oxidative stress reduces inflammatory responses of cultured endothelial cells to TNF-alpha. 1069 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

Systemic inflammation is common in patients with nephropathia epidemica (NE), a European form of hemorrhagic fever. Markers of inflammation were studied in a patient with NE with respiratory insufficiency (patient 1), 18 other patients with NE, and 13 patients with a viral infectious disease other than NE. Neutrophil and monocyte CD11b expression levels, determined by flow cytometry; soluble interleukin (IL)-2 receptor (sIL-2R), IL-6, and IL-8 concentrations, determined by means of Immulite; and soluble E-selectin, determined by ELISA, were higher in patients with NE than in healthy subjects. The findings were not specific for NE and did not correlate with serum creatinine levels, but the findings correlated inversely with mean arterial pressure (sIL-2R and monocyte CD11b expression) and minimum platelet count (sIL-2R, IL-6, neutrophil, and monocyte CD11b expression). Monocyte CD11b expression in patient 1 was extremely high, suggesting that monocytes may contribute to development of lung injury. Severity of inflammation in patients with NE is related to hypotension and platelet consumption but not to renal injury.
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PMID:Systemic inflammation in hemorrhagic fever with renal syndrome correlates with hypotension and thrombocytopenia but not with renal injury. 1083 76

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

Activated neutrophil (PMN) adherence to vascular endothelium comprises a key step for both transendothelial migration and initiation of potentially deleterious release of PMN products. The biogenic amine, dopamine (DA), has been used for several decades in patients to maintain hemodynamic stability. The effect of dopamine on PMN transendothelial migration and adhesion receptor expression and on the endothelial molecules, E-selectin and ICAM-1, was evaluated. PMN were isolated from healthy controls, stimulated with lipopolysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) and treated with dopamine. CD 11b and CD 18 PMN adhesion receptor expression were assessed flow cytometrically. In a separate experiment, the chemoattractant peptide, IL-8, was placed in the lower chamber of transwells, and PMN migration was assessed. Human umbilical vein endothelial cells (HUVEC) were stimulated with LPS/TNF-alpha and incubated with dopamine. ICAM-1 and E-selectin endothelial molecule expression were assessed flow cytometrically. There was a significant increase in transendothelial migration in stimulated PMN compared with normal PMN (40 vs. 14%, P < 0.001). In addition, PMN CD11b/CD18 was significantly upregulated in stimulated PMN compared with normal PMN (252.4/352.4 vs. 76.7/139.4, P < 0.001) as were endothelial E-selectin/ICAM-1 expression compared with normal EC (8.1/9 vs. 3.9/3.8, P < 0.05). After treatment with dopamine, PMN transmigration was significantly decreased compared with stimulated PMN (8% vs. 40%, P < 0.001). Furthermore, dopamine also attenuated PMN CD11b/CD18 and the endothelial molecules E-selectin and ICAM-1 compared with stimulated PMN/EC that were not treated dopamine (174/240 vs. 252/352, P < 0.05 and 4/4.4 vs. 8.1/9, P < 0.05. respectively). The chemoattractant effect of IL-8 was also attenuated. These results identify for the first time that dopamine attenuates the initial interaction between PMN and the endothelium, and consequently, modulates PMN exudation. Thus, biogenic amines, including dopamine, may function as anti-inflammatory cytokines.
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PMID:Dopamine attenuates the chemoattractant effect of interleukin-8: a novel role in the systemic inflammatory response syndrome. 1102 46

The destruction of newly forming tumor vasculature is a promising approach to inhibit tumor growth. The goal of the present study was to investigate whether human lymphocytes gene modified to express a chimeric receptor specific for the angiogenic endothelial cell receptor, KDR, could react against KDR(+) cells. Gene-modified lymphocytes specifically lysed KDR(+) cells and secreted cytokines in response to KDR(+) target cells including human umbilical vein endothelial cells (HUVECs). Anti-KDR lymphocytes induced HUVECs to secrete the chemokine interleukin 8 and upregulate the adhesion molecules VCAM and E-selectin, which may be important in the recruitment of further immune effector cells to tumor. These KDR-specific lymphocytes may be useful in the adoptive immunotherapy of a broad range of cancers by inducing immune-mediated destruction of tumor neovasculature.
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PMID:Generation of gene-modified T cells reactive against the angiogenic kinase insert domain-containing receptor (KDR) found on tumor vasculature. 1111 16

Eosinophils exhibit a rolling interaction with E-selectin-expressing endothelium, and need to be activated by inflammatory mediators to firmly adhere to this surface. This study shows that IL-8 induces a transient arrest of unprimed eosinophils that roll on E-selectin present on TNF-alpha-activated HUVEC in an in vitro flow chamber. This process was antagonized by neutralizing Abs directed against IL-8 showing the specificity of the IL-8 effect. Furthermore, blocking Abs against both alpha(4) and beta(2) integrins inhibited the IL-8-induced transient arrest while these Abs had no effect when they were added separately. The IL-8-induced arrest was pertussis toxin sensitive. Studying the effect of IL-8 in more detail, we evaluated putative changes in intracellular Ca(2+) concentration in eosinophils induced by IL-8. We could show that IL-8 induces a transient rise in intracellular Ca(2+) concentration in approximately 40% of the cells provided that the eosinophils are interacting with endothelial cells or fibronectin-coated surfaces. Together these data show that resting eosinophils respond to IL-8 provided that the cells adhere on physiological surfaces. The induction of a transient arrest provides a new level of chemokine-induced regulation of leukocyte adhesion under flow conditions.
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PMID:IL-8 induces a transient arrest of rolling eosinophils on human endothelial cells. 1112 41

The aim of this work was the evaluation of serum and ascitic fluid levels of chemokines (IL-8, growth-regulated oncogene (Gro-alpha), and monocyte chemotactic protein-1 (MCP-1)), and of soluble adhesion molecules (P-selectin, E-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) in patients with spontaneous bacterial peritonitis (SBP). These compounds were serially analysed in serum and ascitic fluid by ELISA in patients with SBP (n = 20), non-infected cirrhotic controls (n = 12), and healthy controls (n = 15). Infected and non-infected cirrhotic patients showed significantly higher serum levels of adhesion molecules. SBP was associated with significantly higher serum and ascitic fluid levels of IL-8, Gro-alpha and ICAM-1 and with ascitic fluid concentrations of MCP-1. Significantly elevated serum levels of both ICAM-1 and VCAM-1 were detected in patient non-survivors after SBP. Thus, higher ascitic fluid levels of chemokines could be implicated in the peritoneal infiltrate in patients with SBP. Prognostic significance can be attributed to serum levels of ICAM-1 and VCAM-1 in these patients.
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PMID:Serial analysis of serum and ascitic fluid levels of soluble adhesion molecules and chemokines in patients with spontaneous bacterial peritonitis. 1116 98

The blood-borne, erythrocyte-aggregating Borrelia crocidurae, the causative agent of African relapsing fever, have been shown to induce severe cellular lesions in mice. In this paper, we present the first report of how the endothelium is stimulated during an African relapsing fever B. crocidurae infection. B. crocidurae co-incubated with cultured human umbilical vein endothelial cells (HUVECs) activated endothelium in such way that E-selectin and intercellular adhesion molecule 1 (ICAM-1) became upregulated in a dose- and time-dependent fashion, as determined by a whole-cell enzyme-linked immunosorbent assay (ELISA). The upregulation was reduced by treatment that killed the bacteria, suggesting that viability is important for the stimulation of HUVECs by B. crocidurae. Furthermore, conditioned medium from HUVECs stimulated with B. crocidurae contained interleukin (IL)-8, which is a chemotactic agent for neutrophils. Activation of HUVECs by B. crocidurae resulted in migration of subsequently added neutrophils across the endothelial monolayers, and this migration was inhibited by antibodies to IL-8. The activation of endothelium by B. crocidurae may constitute a key pathophysiological mechanism in B. crocidurae-induced vascular damage.
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PMID:The relapsing fever spirochaete, Borrelia crocidurae, activates human endothelial cells and promotes the transendothelial migration of neutrophils. 1120 11

During surgery, incision of the skin under aseptic conditions is performed. Despite the absence of noxious agents, an inflammatory response may be induced. We studied the local inflammatory response in human skin as a result of surgical intervention, under aseptic conditions. Elective standardized vascular surgery served as a model. A series of skin biopsies was taken from the wound edge at different time points after first incision. Biopsies, directly taken at first incision were considered to represent normal skin. Additional biopsies were taken at 30 min after the start of surgery and just before closure of the wound, maximally 270 min after surgery. Kinetics of recruitment of cells, expression of adhesion molecules and the presence of pro-inflammatory cytokines was studied. Granulocytes were observed at first at 30 min after incision of the skin and their number increased in time. This granulocyte infiltration is paralleled by E-selectin expression on endothelial cells, which also was observed at first at 30 min after surgery with a further increase in number in time. Incision of the skin did not change P-selectin, ICAM-1, VCAM-1, TNFalpha, IL1alpha, IL1beta, IL6 and IL8 expression. These results show that incision of the skin under aseptic conditions during elective standardized vascular surgery induces local nonspecific cellular inflammation.
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PMID:Local cellular inflammation as a result of elective standardized vascular surgery. 1136 95

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