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)

IL-8 belongs to the family of chemotactic cytokines and may play an important role in the inflammatory response. In the current studies, a murine mAb (DM/C7) to human rIL-8 was found to have protective effects in inflammatory lung injury in rats. DM/C7 was nonreactive with the rat cytokine-induced neutrophil chemoattractant peptide. In vivo, DM/C7 blocked the glycogen-induced accumulation of neutrophils in rats and was highly protective against lung and dermal vascular injury after deposition of IgG immune complexes. The latter model of injury has recently been shown to be E-selectin dependent. The protective effects of DM/C7 correlated with reduced tissue accumulation of neutrophils, as measured by myeloperoxidase content. DM/C7 reacted with an epitope expressed by TNF-alpha-stimulated rat pulmonary artery endothelial cells and with the pulmonary vascular endothelium after intrapulmonary deposition of IgG immune complexes. In the model of IgG immune complex-induced lung injury, the protective effects of DM/C7 were abolished by prior absorption of the antibody with human rIL-8. Polyclonal antibody to cytokine-induced neutrophil chemoattractant peptide failed to protect against IgG immune complex-induced vascular injury even though this antibody blocked the in vitro chemotactic activity of cytokine-induced neutrophil chemoattractant. In the model of rapidly developing lung injury due to systemic activation of C after infusion of cobra venom factor, DM/C7 was not protective. As well, in the neutrophil-independent model of IgA immune complex-induced lung injury, treatment with DM/C7 was not protective. These data indicate that in inflammatory lung injury that is linked to E-selectin-dependent recruitment of neutrophils in rats, antibody to human IL-8 also blocks recruitment of neutrophils and thereby affords protection against lung injury. The data suggest the presence of an IL-8-like product in this model of lung injury.
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PMID:Inhibition of lung inflammatory reactions in rats by an anti-human IL-8 antibody. 839 May 38

The CD45RO+ population of lymphocytes from human blood contains a higher proportion of locomotor cells than the CD45RA+ population. Direct from blood there were few locomotor lymphocytes (< 15%), but, among these, a higher proportion of CD45RO+ than of CD45RA+ cells responded to the chemotactic stimuli, foetal calf serum (FCS) and interleukin-2 (IL-2) in polarization assays. Likewise, after overnight culture, a higher proportion of CD45RO+ cells responded to IL-8. Culture for 24-72 hr in activators such as anti-CD3, purified protein derivative (PPD), phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) or in an allogeneic mixed leucocyte reaction (AMLR) increased the proportion of locomotor lymphocytes to 20-60%, and the CD45RO+ subset showed proportionately more polarized cells than the CD45RA+ subset after culture with all the above activators. Preferential migration of CD45RO+ cells into collagen gels was also seen after culture in antigenic stimuli (PPD or AMLR) but not with polyclonal activators (alpha CD3 or Con A). Double labelling showed that, within the CD4+ and CD8+ subsets, antigen-stimulated CD45RO+ T cells invaded collagen gels in higher proportions than CD45RA+ T cells. Clustering of lymphocytes with accessory cells is an essential prerequisite for locomotion and, after culture in alpha CD3, CD45RO+ lymphocytes were found preferentially in clusters with monocytes. In all of the above populations, CD45RO+ lymphocytes were larger in size. These findings suggest that, not only selective adhesion to vascular endothelium as reported earlier, but also selective locomotion recruits CD45RO+ lymphocytes into sites of inflammation.
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PMID:Locomotor responses of human CD45 lymphocyte subsets: preferential locomotion of CD45RO+ lymphocytes in response to attractants and mitogens. 843 7

Numerous cytokines are present within inflammatory foci. Interleukin-1 (IL-1) and tumour necrosis factor (TNF) play a major role in coordinating mechanisms which command inflammation. Upon their action, many different cells produce lipidic mediators, proteolytic enzymes, and free radicals, all directly responsible for the noxious effects observed. IL-1 and TNF exert cytotoxic effects on vascular endothelium, cartilage, bone and muscle. Such cytokines as interferon-gamma, IL-3 or granulocyte-macrophage colony stimulating factor amplify the inflammatory response by increasing the production of IL-1 and TNF. The latest trigger the release of chemokines such as IL-8 and macrophage chemoattractant protein-1, the chemotactic activity of which participates in the recruitment of leukocytes within the foci of inflammation. IL-6, abounds in inflammatory processes and induces the production by hepatocytes of acute phase proteins. The same applies to IL-1, TNF, IL-11, the leucocyte inhibitory factor, and the transforming growth factor-beta. The later also processes a number of anti-inflammatory activities and, like IL-4, IL-10 and IL-13, can inhibit IL-1 and TNF production. Such property has also been mentioned for interferon-alpha. These anti-inflammatory cytokines can also counteract some of the IL-1 and TNF activities such as those reported during the coagulation process. Furthermore, these anti-inflammatory cytokines can induce the production of the IL-1 receptor antagonist which prevents the activities initiated by IL-1. Soluble TNF receptors, released during inflammation, are the direct inhibitors for TNF. Glucocorticoids, produced following a cascade of events initiated by IL-1, TNF and IL-6, involving the neuroendocrine axis, also inhibit proinflammatory cytokine productions. The concept of "cytokine network" therefore, perfectly illustrates the participation of these mediators in inflammation mechanisms.
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PMID:[Cytokines in inflammation]. 856 67

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.
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PMID:Transforming growth factor-beta 1 inhibits the production of IL-8 and the transmigration of neutrophils through activated endothelium. 868 38

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.
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PMID:Control of endothelial leukocyte adhesion molecules by fatty acids. 872 95

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.
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PMID:Adenosine inhibits cytokine release and expression of adhesion molecules by activated human endothelial cells. 877 15

Lyme disease is caused by infection with Borrelia burgdorferi, and is characterized by bacterial persistence and inflammation in a number of host tissues. B. burgdorferi outer surface lipoproteins possess cytokine stimulatory properties that may be responsible for localized inflammation. B. burgdorferi presence is correlated with severity of disease, and the pathology of many tissues, particularly the arthritic joint, is consistent with localized cytokine production. Spirochete invasion of tissues requires interaction with and penetration of vascular endothelium, suggesting endothelial cells may participate in the inflammation of Lyme disease. In this study, outer surface protein A (OspA), a model B. burgdorferi lipoprotein, was found to be a potent stimulant of nuclear factor-kappa B (NF-kappa B) nuclear translocation in human endothelial cells, resulting in nuclear levels similar to those seen in response to known inflammatory mediators. Only the lipid-modified OspA had activity, and activity was not due to contamination with LPS. Nuclear NF-kappa B was detectable within 15 min, suggesting that OspA directly mediates NF-kappa B nuclear translocation. OspA also rapidly up-regulated endothelial cell production of several proteins whose transcription is dependent on NF-kappa B: the cytokine IL-6; the chemokine IL-8; and the adhesion molecules E-selectin, VCAM-1, and ICAM-1. The adhesion molecules were functional, as demonstrated by enhanced binding of neutrophils to OspA-stimulated endothelial monolayers. These data suggest that OspA may initiate synthesis of many proteins essential for localized inflammation via the direct activation of NF-kappa B-dependent transcription. These observations suggest that the interaction of B. burgdorferi lipoproteins with the endothelium may directly induce the inflammation responsible for the symptoms of Lyme disease.
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PMID:Borrelia burgdorferi outer membrane protein A induces nuclear translocation of nuclear factor-kappa B and inflammatory activation in human endothelial cells. 890 37

The function of vascular endothelial cells is to adjust blood vessel tonus, which contributes to maintaining homeostasis within blood vessels. However, inflammatory cytokines are produced in response to invasion by stimulating vascular endothelial cells and sometimes lead to shock or multiple organ failure. In the present study, we assessed cytokines in sepsis and septic shock, and various factors that are said to have a damaging effect on vascular endothelium. Endotoxin was measured by endotoxin-specific methods. Tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 8 (IL-8) were measured by enzyme-linked immunosorbent assay (ELISA). Endothelin-I was measured by radioimmunoassay (RIA). Nitric oxide was measured as metabolites of nitrite and nitrate oxides (NOx) by a method based on the Griess method. Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGF 1 alpha) were both measured by RIA. All of the factors except endotoxin were significantly higher in the septic shock group than in the non-shock group and significantly higher in the non-survivor group than in the survivor group. Significant correlations were also found between endothelin-1 and NOx and between TXB2 and PG1 alpha. Significant correlations were also found between TNF-alpha and IL-6, endothelin-1, NOx and TXB2, but no significant correlations were detected between any of them and endotoxin. In serious diseases such as septic shock, the vascular endothelial constricting factors, endothelin and TXB2, and the blood vessel relaxing factors NOx and PGF1 alpha increase almost simultaneously. This suggests that the body's regulating mechanisms are disrupted in these serious conditions. The results of this study also suggest that inflammatory cytokines may be involved in stimulating the production of these factors.
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PMID:Functional modification of vascular endothelial cells by cytokines during septic shock. 894 12

There is increasing interest in the role of blood polymorphonuclear leukocytes (PMNs) in the pathogenesis of sickle cell crisis. We studied the adherence of PMNs from 18 sickle cell patients in crisis, 25 out of crisis, and 43 healthy subjects (controls) to monolayers of human umbilical cord endothelium that were either untreated or pretreated with tumor necrosis factor alpha (TNFalpha). Overall, the PMNs from patients in crisis were more adherent than control PMNs to untreated endothelial monolayers (mean 53% increase; P < .001) and TNFalpha-treated monolayers (mean 41% increase; P < .002). Increased adhesiveness was not associated with an abnormal expression of CD11a, CD11b, CD11c, CD18, CD62L, or CD15. There was an increase in the number of PMNs expressing CD64 in patients in crisis (median value, 44%) compared with patients out of crisis (median, 21%; P = .025) and controls (median, 6.5%; P < .001). Sera from patients in crisis had normal levels of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-gamma, TNFalpha, interleukin-1 (IL-1), IL-6, or IL-8 and did not modify the adherence of PMNs or their expression of CD64. Only IFN-gamma induced CD64 expression on PMNs, but this effect was not associated with enhanced binding to endothelium. Because PMNs bound to endothelial monolayers were CD64(+) and CD64-enriched PMNs were 7 times more adherent to endothelial monolayers than CD64-depleted PMNs, it is likely that CD64 is a marker of adherent PMNs. Two of the three anti-CD64 antibodies used in our antibody blocking studies (clones 32.2 and 197) partially inhibited the binding of sickle cell PMNs to untreated endothelium (mean inhibitions of 33% [P = .01] and 21% [P = .03], respectively), whereas only one (clone 197) inhibited binding to TNFalpha-treated endothelium (mean inhibition, 29%; P = . 004). In some patients with sickle cell disease, an enhanced PMN adhesion to vascular endothelium could contribute to the vascular occlusion that characterizes the acute crisis of the disease.
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PMID:Blood polymorphonuclear leukocytes from the majority of sickle cell patients in the crisis phase of the disease show enhanced adhesion to vascular endothelium and increased expression of CD64. 941 94

Our study aims to determine whether anti-dsDNA exerts any effect on the gene expression of IL-8 or TGF-beta in cultured HUVEC. Both cytokines have angiogenic effect on endothelial cells. IgG was purified from 19 patients with SLE and from 19 healthy controls. Anti-dsDNA-depleted polyclonal IgG was also prepared from serum IgG of lupus patients by affinity chromatography with DNA cellulose column. Compared with either control IgG or anti-dsDNA-dep-IgG, HUVEC incubated with anti-dsDNA-containing-IgG expressed higher levels of IL-8 mRNA (p = 0.0001) and TGF-beta 1 mRNA (p = 0.0014). We demonstrated a significant increase in the percentage of cells with fragmented DNA in HUVEC incubated with anti-dsDNA-containing-IgG compared with those incubated with anti-dsDNA-dep-IgG, supporting the notion that anti-dsDNA may exert a direct apoptotic effect on cultured endothelial cells. Our study provides in vitro evidence that anti-dsDNA could play an important pathogenetic role in inducing inflammatory injury of vascular endothelium in SLE.
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PMID:Effect of anti-DNA autoantibodies on the gene expression of interleukin 8, transforming growth factor-beta, and nitric oxide synthase in cultured endothelial cells. 943 8

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