UNIPROT:P10145 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

New selenium-containing compounds behave as GPx mimics and protect endothelial cells (HUVEC) from damage upon exposure to 55 microM linoleic acid hydroperoxide or to 200 microM hydrogen peroxide. The simultaneous presence of the GPx mimic and the hydroperoxyde is not necessary, since a pre-treatment of endothelial monolayers with 1 to 10 microM of such compounds, preserves their morphology, their cell density and their longer-term viability. The compounds which are most efficient in this model of oxidative stress also protect endothelial monolayers which have been incubated with an excess (10:1) of polymorphonuclear neutrophils (PMN) and with 1 ng/ml of TNF-alpha, if such monolayers are pre- and co-treated (10 microM). They inhibit the adhesion of activated neutrophils which show-up as polymorphous and very dense particles, in the vicinity of which endothelial alterations can be seen. The inhibition of leucocyte adhesion and that of endothelial activation/alteration have been quantified by means of immunoassays of myeloperoxidase and von Willebrand factor (vWf). The lead-compound BXT-51072 is not a direct inhibitor of the NADPH oxidase of PMN. TNF-alpha alone induces the endothelial release of Interleukin-8 (Il-8) as well as the expression of P- and E-selectin. The extent and the kinetics of inhibition of such processes by compound BXT-51072 would explain several of the effects observed in the presence of PMN. The GPx mimics also inhibit the endothelial production of Il-8 which is induced by Interleukin-1 alpha. Finally, compound BXT-51072 inhibits the endothelial expression of the adhesion factor VCAM-1 which is more slowly induced by TNF-alpha. Such antioxidant catalysts therefore protect endothelial cells from the toxic effects of TNF-alpha through mechanisms which include a down-regulation of cytokines and cell-adhesion factors.
...
PMID:[Antioxidant and anti-inflammatory protection of vascular endothelial cells by new synthetic mimics of glutathione peroxidase]. 867 32

A central mechanism of inflammation is the activation of vascular endothelium by the inflammatory cytokines TNF-alpha and IL-1. These cytokines induce the expression of adhesion molecules, the elaboration of chemokines, and the transendothelial migration of white cells. TGF-beta 1 has anti-inflammatory properties, is expressed in the vessel wall, and has previously been shown to inhibit leukocyte adhesiveness to the endothelium at least in part by inhibiting the expression of E-selectin. We now show that TGF-beta 1 also inhibits the migration of neutrophils through endothelial monolayers activated by TNF-alpha. At a dose of 10 U/ml TNF-alpha, the transmigration of neutrophils was inhibited 42.7 +/- 7.9% (n = 8) by 0.2 ng/ml TGF-beta 1. Furthermore, TGF-beta 1 inhibited, in a time- and dose-dependent fashion, the elaboration of IL-8 by TNF-activated endothelial cells by between 33 and 78% (TNF doses from 100 down to 0.1 U/ml) and the elaboration of mRNA for IL-8 by 69%. TGF-beta 1 treatment did not significantly alter the TNF-induced IL-8 mRNA stability, suggesting that the mechanism of action of TGF-beta 1 is on gene transcription. Neutrophil transmigration through cytokine-activated endothelium involves both IL-8-dependent and IL-8-independent mechanisms. Using an anti-IL-8 Ab, we show that TGF-beta 1 inhibits only the IL-8-dependent pathway, but does not affect the IL-8-independent transendothelial migration mechanism. These and our previous results show that TGF-beta1, achieves its anti-inflammatory properties by inhibiting the expression of at least two genes, E-selectin and IL-8, which are essential in the inflammatory pathway.
...
PMID:Transforming growth factor-beta 1 inhibits the production of IL-8 and the transmigration of neutrophils through activated endothelium. 868 38

We previously showed that endothelial cells (EC) from the vasculature of human solid tumors have a decreased expression of intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 as compared with normal tissue EC. This effect is explained by EC exposure to angiogenic factors. It is known that upregulation of endothelial adhesion molecules (EAM) is a sign of EC activation in inflammatory responses. We therefore tested the effect of angiogenic factors on upregulation of EAM on tumor EC and human umbilical vein EC (HUVEC) by proinflammatory cytokines. Incubation of tumor-derived EC in tumor necrosis factor alpha (TNF alpha) did result in expression levels of only 20% of the level of similarly treated normal tissue-derived EC. Pretreatment of HUVEC with 10 ng/ml basic fibroblast growth factor (bFGF) for 3 days, before TNF alpha- or interleukin-1 alpha (IL-1 alpha) stimulation, resulted in ICAM-1 levels of only 30% to 60% of cells without pretreatment. Also, the induction of vascular EC adhesion molecule-1 (VCAM-1) and E-selectin by TNF alpha was significantly inhibited by prior exposure to bFGF. Vascular endothelial growth factor had similar but less prominent effects. The effect of transforming growth factor-beta and IL-8 was studied as well. The functional relevance of the finding of a decreased EC inflammatory response was confirmed by adhesion assays. Our results show that tumor angiogenesis induces EC anergy. This may serve as a tumor-protecting mechanism by impairing the development of an efficient leukocyte infiltrate in tumors.
...
PMID:Tumor angiogenesis is accompanied by a decreased inflammatory response of tumor-associated endothelium. 869 14

Endothelial cells have the potential to influence significantly the host immune response to blood-borne microbial pathogens, such as Candida albicans. We investigated the ability (of this organism to stimulate endothelial cell responses relevant to host defense in vitro. Infection with C. albicans induced endothelial cells to express mRNAs encoding E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, interleukin 6, interleukin 8, monocyte chemoattractant protein 1, and inducible cyclooxygenase (cox2). All three leukocyte adhesion molecule proteins were expressed on the surfaces of the endothelial cells after 8 h of exposure to C. albicans. An increase in secretion of all three cytokines was found after 12 h of infection. Cytochalasin D inhibited accumulation of the endothelial cell cytokine and leukocyte adhesion molecule mRNAs in response to C. albicans, suggesting that endothelial cell phagocytosis of the organism is required to induce this response. Live Candida tropicalis, Candida glabrata, a nongerminating strain of C. albicans, and killed C. albicans did not stimulate the expression of any of the cytokine or leukocyte adhesion molecule mRNAs. These findings indicate that a factor associated with live, germinating C. albicans is required for induction of endothelial cell mRNA expression. Furthermore, since endothelial cells phagocytize killed C. albicans, phagocytosis is likely necessary but not sufficient for this organism to stimulate mRNA accumulation. In conclusion, the secretion of proinflammatory cytokines and expression of leukocyte adhesion molecules by endothelial cells in response to C. albicans could enhance the host defense against this organism by contributing to the recruitment of activated leukocytes to sites of intravascular infection.
...
PMID:Candida albicans stimulates cytokine production and leukocyte adhesion molecule expression by endothelial cells. 869 86

The cutaneous lymphocyte-associated antigen (CLA) is a carbohydrate epitope present on memory/effector T cells that infiltrate inflamed skin. E-selectin is the ligand for CLA and is induced under inflammation on endothelial cells. CLA was originally postulated as a phenotype marker for skin-associated T cells. We studied the specific in vitro response to skin-associated allergens of CLA+ and CLA-CD45RO+ T cells in atopic dermatitis (AD) and contact dermatitis (CD), which represent two well-characterized T cell-mediated cutaneous allergic inflammations. Whereas CLA+ T cells from AD patients preferentially responded to house dust mite (HDM) and CLA+ T cells from nickel CD patients showed an increased response to nickel, CLA-T cells showed very little response in both cases. In contrast, tetanus toxoid, a systemically acting antigen, induced a proliferative response in both CLA+ and CLA- cells. Interestingly the response to HDM in patients with asthma +/- AD was preferentially found in the CLA- subset indicating the involvement of different homing receptors for mucosal tissues. Moreover, CLA+ T cells showed enhanced migration through activated human umbilical vein endothelial cell monolayers compared to CLA- T cells. The CLA binding to E-selectin is initially responsible for the extravasation that also involves VLA-4/VCAM-1 and LFA-1/ICAM-1 interactions. We have recently identified IL-8 as an endothelial cell-derived chemokine and the IL-8 receptor type B which control CLA+ T cell migration. Such a CLA-mediated migration would localize memory/effector T cells that respond to antigens and reach the body through inflamed skin. Our data support the existence of a regionalization of the immune system and in particular of the skin immune system. It may allow an efficient distribution of the immune defense to different sites of the body.
...
PMID:Skin-homing T cells in human cutaneous allergic inflammation. 872 46

Dietary balance of long-chain fatty acids (FA) may influence human susceptibility to pathological processes which involve the interaction of leukocytes with vascular endothelium, such as atherogenesis and inflammation. Such interaction is largely mediated by the de novo or increased expression of endothelial leukocyte adhesion molecules on vascular endothelial cells, able to tether and stably bind leukocytes onto the vessel wall, and by the production of leukocyte chemoattractants. Endothelial cells do not normally support high levels of leukocyte adhesion. They do so, however, when exposed to a number of stimuli, such as oxidized low density lipoprotein bacterial lipopolysaccharides, and inflammatory cytokines, which induce phenotypic changes generally referred to as "endothelial activation." We compared various FA in their ability to modulate endothelial activation by cytokines. FA included linoleic, arachidonic, oleic, eicosapentaenoic and, docosa-hexaenoic acid (DHA) as representatives of the n-6, n-3 polyunsaturated FA and of the monounsaturated FA. The n-3 FA DHA, and, to a lesser extent, oleate, at nutritionally compatible concentrations, were able to reduce endothelial expression of Vascular Cell and Adhesion Molecule-1 (VCAM-1). In further studies, DHA dose- and time-dependently reduced also the expression of E-selectin, Intercellular Adhesion Molecule-1, interleukin (IL)-6 and IL-8, in response to IL-1, IL-4, tumor-necrosis factor, or bacterial endotoxin. The magnitude of this effect paralleled its incorporation into cellular phospholipids. Also, coordinate with reduced surface adhesion molecule expression, DHA reduced the adhesion of human monocytes and of monocytic U937 cells to cytokine-stimulated endothelial cells. These effects were accompanied by a quantitatively consistent reduction in VCAM-1 mRNA, indicating a pretranslational control of adhesion molecule gene expression. These novel properties of FA as modulators of endothelial activation may help to explain the influence of dietary FA intake on atherogenesis and inflammation.
...
PMID:Control of endothelial leukocyte adhesion molecules by fatty acids. 872 95

Endothelial cell (EC) activation plays a key role in inflammation, thrombosis and organ rejection. Normally, EC are in a quiescent state in which their function is to prevent coagulation and thrombosis, and to participate in the regulation of leukocyte migration from the bloodstream into the tissue. Upon activation with cytokines or other stimuli, EC up-regulate a number of genes, including E-selectin (ELAM-1), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, interleukin (IL)-1, IL-8, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), MCP-1 (monocyte chemoattractant protein-1) and endothelial cell inducible gene (ECI-6). Arachidonic acid (AA) is produced by several cell types, including EC, and acts on various cells. We report here that AA inhibits the up-regulation of some, but not all genes that are induced with EC activation in a dose-dependent manner. AA suppresses TNF-alpha, IL-1 alpha, LPS or PMA-induced E-selectin expression, as well as mRNA accumulation of E-selectin, ICAM-1 and IL-8 stimulated by TNF-alpha. The inhibition appears to be at the level of transcription. At the same time under the same conditions AA does not, repress mRNA accumulation for PAI-1, ECI-6, MCP-1 and VCAM-1. We suggest that the induced expression of AA with EC activation may result in a negative feedback loop regulating further activation.
...
PMID:Selective suppression of endothelial cell activation by arachidonic acid. 876 41

Ischemia induces excessive ATP catabolism with subsequent local release of its metabolite adenosine, an autacoid with anti-inflammatory properties. Because activation of the vascular endothelium is critical to the inflammatory host response during ischemia and reperfusion, the effects of adenosine on two major determinants of endothelial cell activation (i.e., the release of proinflammatory cytokines and the expression of adhesion molecules) were studied. Adenosine dose dependently inhibited the release of interleukin (IL)-6 and IL-8 by stimulated human umbilical vein endothelial cells (HUVEC). Expression of E-selectin and vascular cell adhesion molecule 1 (VCAM-1), but not intercellular adhesion molecule 1 (ICAM-1), by activated HUVEC was also reduced by adenosine. Inhibition of endogenous adenosine deaminase activity by erythro-9-(2-hydroxy-3-nonyl)adenine or 2'-deoxycoformycin strongly enhanced the inhibitory effects of exogenous adenosine on cytokine release and expression of E-selectin and VCAM-1. However, a clear role for specific adenosine receptors in the described inhibitory events could not be established. Together, these data imply that the vascular endothelium constitutes an important target for the anti-inflammatory actions of adenosine.
...
PMID:Adenosine inhibits cytokine release and expression of adhesion molecules by activated human endothelial cells. 877 15

Activated natural killer (NK) cells have been found in rejecting discordant xenografts and may contribute to endothelial cell (EC) activation and damage. The transcription of genes associated with EC activation, such as E-selectin and interleukin (IL)-8, is regulated by the transcription factor NF-kappaB. In resting EC, NF-kappaB is complexed within the cytoplasm to I(kappa)B(alpha), and EC activation leads to dissociation of the I(kappa)B(alpha)-NF-kappaB complex and nuclear translocation of NF-kappaB. We investigated whether overexpression of I(kappa)B(alpha) in EC, using adenoviral gene transfer, could block NF-kappaB translocation, thereby inhibiting NK cell-mediated EC activation. Co-culture of human NK cells with porcine EC resulted in a threefold increase in E-selectin expression after 4 hr and secretion of greater than 650 pg/ml porcine IL-8 over 24 hr. Overexpression of I(kappa)B(alpha) inhibited the NK cell-mediated induction of E-selectin expression and IL-8 secretion, whereas overexpression of P-galactosidase did not. The inhibition of EC activation was not due to variation in NK-EC adhesion, as the level of adhesion was similar between adenovirally infected and noninfected EC over 4 hr. The level of NK cell-mediated EC cytotoxicity was not significantly different after 4 hr of co-culture, but after 24 hr, cytotoxicity was increased in virally infected cells. Cytotoxicity was more marked in cells overexpressing I(kappa)B(alpha) than cells overexpressing beta-galactosidase. SLA class I and the induction of SLA class II antigen in response to interferon-gamma treatment were reduced in cells infected with adeno-I(kappa)B(alpha) and empty adenovirus, demonstrating that viral infection alone can influence EC biology. Overexpression of I(kappa)B(alpha) using adenovirus provides a novel approach to inhibiting NK cell-mediated EC activation, but additional strategies will be required to inhibit NK cell-mediated cytotoxicity.
...
PMID:Adenoviral-mediated overexpression of I(kappa)B(alpha) in endothelial cells inhibits natural killer cell-mediated endothelial cell activation. 887 92

Poor initial graft function may increase postoperative morbidity including the risk of early allograft rejection. Various mediators, including immunostimulatory cytokines, may be released during reperfusion in relation to the extent of preservation and reperfusion injury. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines, adhesion molecules, extracellular matrix (ECM) parameters, and neopterin at predefined time-points during and after transplantation. To estimate the origin of cytokine release, blood was obtained central and hepatic venously for the first 48 hr after reperfusion and subsequently from a peripheral vein. One-year patient survival was 88.9%; no relation to initial graft function was observed. Poor initial graft function failed to increase the risk for subsequent infectious complications but was associated with an increased risk of early allograft rejection. The incidence of steroid-resistant rejection was significantly increased in patients with poor initial graft function (35.7% versus 12.7% in patients with good and moderate initial graft function; P < or = 0.05). Various cytokines, adhesion molecules, and ECM parameters including sTNF-RII, sIL-2R, IL-8, IL-10, sVCAM-1, E-selectin, hyaluronic acid, sialic acid, and laminin correlated significantly with the extent of preservation and reperfusion injury. Although none of these parameters was more appropriate in determining the extent of preservation and reperfusion injury than currently established parameters (AST, ALT, and color and amount of bile production), the combined increase in these parameters may not only promote tissue repair but may also perpetuate liver allograft injury and thereby cause significant morbidity. Besides cytokines and adhesion molecules, the ECM may play a pivotal role in determining repair or ongoing tissue injury. Ongoing changes at the microvasculature and basement membrane may result in an increase of local and circulating cytokines and adhesion molecules, which increase the risk of subsequent early allograft rejection. Furthermore, the increase in sTNF-RII, E-selectin, and laminin during reperfusion was predictive of subsequent development of acute allograft rejection. These observations may be of value for further strategies to decrease reperfusion injury and prevent early allograft rejection.
...
PMID:The release of cytokines, adhesion molecules, and extracellular matrix parameters during and after reperfusion in human liver transplantation. 890 Mar 13

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>