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)

Granulocyte colony-stimulating factor (G-CSF) was administered at a dose of 7.5 or 10 micrograms/kg s.c. once daily for 6d (days 1-6) to two groups consisting of eight and six healthy volunteers. The administration of G-CSF resulted in a rapid decrease in neutrophil counts and serum levels of the secondary granule protein, human neutrophil lipocalin (HNL) after 30 min, followed by a recovery and gradual increase within 180 min. The number of circulating neutrophils and plasma and serum levels of neutrophil secondary granule proteins were dramatically elevated on day 2 (1 d after the administration of G-CSF) and stayed so until day 7. The plasma levels of HNL and lactoferrin (LF) showed a biphasic pattern with peaks at day 2 and days 5-7, and remained highly elevated at day 12. The serum levels of HNL and LF increased rapidly (about 8-fold and 6-fold, respectively) on day 2 and stayed elevated until day 7, subsequently returning to baseline levels. At day 5, neutrophil release induced in vitro by f-MLP was significantly enhanced. The cellular contents of HNL and LF were reduced to about 50% of levels before G-CSF administration at day 5. The release of lactoferrin and HNL, but not of myeloperoxidase (MPO), was slightly enhanced after preincubation of isolated normal neutrophils with G-CSF in vitro, but no obvious release of these proteins was observed with G-CSF alone. The administration of G-CSF resulted in a dramatic increase in the alkaline phosphatase (AP) activity in the plasma membrane, with maximal activity occurring at day 5. Furthermore, during administration of G-CSF, TNF-alpha in plasma increased about 25-fold. TNF-alpha started to rise at day 2 and peaked at day 6. After discontinuation of G-CSF the levels of TNF-alpha gradually decreased. The elevated levels of TNF-alpha (tumour necrosis factor-alpha) were temporally correlated to the other signs of neutrophil activation. GM-CSF and IL-8, however, were not detected in plasma. Our data suggest that G-CSF affects the neutrophils not only directly but also indirectly by the induction of the production of other cytokines such as TNF-alpha.
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PMID:The effect of granulocyte colony-stimulating factor (G-CSF) on the degranulation of secondary granule proteins from human neutrophils in vivo may be indirect. 865 73

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.
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PMID:[Antioxidant and anti-inflammatory protection of vascular endothelial cells by new synthetic mimics of glutathione peroxidase]. 867 32

Exposure of healthy subjects to ozone is associated with increases in cellular and biochemical markers of inflammation in bronchoalveolar lavage fluid. To determine if analysis of induced sputum might similarly reveal the pulmonary inflammatory effects of ozone exposure, we performed cellular and biochemical analysis of induced sputum collected 4 hr after air and ozone (0.4 ppm for 2 hr) exposures from 10 healthy subjects (age 30.0 +/- 5.0 years; 5 females) in a randomized crossover study in which exposures were separated by 2 weeks. We found that the total number of nonsquamous cells was significantly higher after ozone exposure than after air exposure (7.4 vs 3.9 x 10(5)/ml, P < 0.05) as was the percentage of the nonsquamous cells that were neutrophils (80.0 +/- 7.0% vs 51.0 +/- 20.0%, P < 0.05) and the levels of myeloperoxidase in the sputum fluid phase (1.6 +/- 0.6 vs 1.3 +/- 0.6 microg/ml, P < 0.05). In addition, IL-6 and IL-8 levels were higher after ozone than after air exposures, but not significantly so (44.5 +/- 32.4 pg/ml vs 26.8 +/- 30.7 pg/ml, P = 0.11; 1.5 +/- 0.5 ng/ml vs 1.1 +/- 0.6 ng/ml, P = 0.09). Mucin-like glycoprotein levels were also not significantly different between exposures (1.6 +/- 0.9 mg/ml vs 1.3 +/- 1.0 mg/ml, P = 0.26). We conclude that analysis of induced sputum is a useful noninvasive method for studying the pulmonary response to ozone exposure in healthy subjects.
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PMID:Analysis of induced sputum after air and ozone exposures in healthy subjects. 867 83

Within the gastroduodenal mucosa Helicobacter pylori infection stimulates local production of a range of proinflammatory and immunoregulatory cytokines, neutrophil infiltration, specific T- and B-cell responses and the development of gastric lymphoid follicles. Following bacterial eradication this mucosal inflammatory response resolves. Infiltrating neutrophils are likely to be one of the major mediators of mucosal damage. Neutrophil activation, including reactive oxygen metabolite production and the release of myeloperoxidase, will be induced directly by bacterial factors and indirectly through products of complement activation, bioactive lipids and host-derived cytokines. Interleukin-8, and related peptides of the chemokine family secreted by gastric epithelial cells, are likely to be important host mediators inducing neutrophil migration to sites of infection. Epithelial IL-8 is upregulated by TNF-alpha and IL-1 and directly by H. pylori strains expressing the CagA phenotype. The extent of mucosal injury may reflect bacterial density, the variability of different strains of H. pylori to induce chemokine expression in epithelial cells and the oxidative burst in neutrophils. Recent evidence from in vivo and in vitro studies shows that CagA+ VacA+ strains of H. pylori are associated with enhanced inflammatory responses and mucosal damage. Defining the specific bacterial mediators of mucosal inflammation will be important in elucidating the role of H. pylori in the pathogenesis of gastroduodenal disease.
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PMID:Gastric mucosal inflammatory responses to Helicobacter pylori. 873 Feb 57

A fusion protein was generated by genetic engineering which combined a Fab fragment of a monoclonal antibody directed to the human epidermal growth factor receptor with the biologically active N-terminally truncated 2-72 amino acid form of the human chemokine IL-8. The Fab IL-8 fusion protein was expressed in E. coli and antibody binding and IL-8 activity were determined. Our data indicate that the N-terminus of IL-8 remains functional for receptor interaction. The fusion protein showed specific binding to IL-8 receptors, induced IL-8 mediated chemotactic activity, and the release of MPO activity. However, N-terminal fusion of IL-8 to the carboxyl terminus of the Fab fragment resulted in reduced binding to IL-8 receptors and consequently to reduced biologic activity of IL-8. The affinity of the antibody arm for EGF-R was improved when compared to a monovalent Fab. Fusion proteins as described herein may represent improved therapeutics for cancer therapy based on their potential to selectively increase and prolong cytokine concentration in the tumour. Since chemokines such as IL-8 recruit effector cells and stimulate effector cell function in situ, a lymphocyte-independent anti-tumour activity followed by tumour-specific immunity could be proposed.
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PMID:A fusion protein of IL-8 and a Fab antibody fragments binds to IL-8 receptors and induces neutrophil activation. 883 36

Acute poststreptococcal glomerulonephritis (APSGN) is characterized by diffuse glomerular hypercellularity, primarily as a result of accumulation of neutrophils (exudative glomerulonephritis), increase in intrinsic glomerular cells, and transient pathological mesangial matrix expansion. Cytokines and growth factors are supposed to play an important role as mediators of inflammation and as progression factors in various renal disorders. Interleukin-8 is a recently described cytokine, defined as a selective activator and chemoattractant of polymorphonuclear leukocytes (PMNL) and transforming growth factor (TGF)-beta plays a central role in the accumulation of pathological extracellular matrix in glomerulonephritis. This study analyzed the biopsies of ten patients with APSGN, using immunohistochemistry (avidin-biotin complex/horseradish peroxidase method) using monoclonal antibodies anti-IL-8, anti-TGF-beta 1, beta 2, beta 3. Controls consisted of non-immune mouse serum, or anti-TGF-beta preabsorbed with human recombinant TGF-beta. Compared with normal renal tissue, and minimal change disease, an increased glomerular IL-8 and TGF-beta staining was observed in all of the biopsies. Furthermore, in one patient, we observed a weak deposit of TGF-beta in tubulointerstitium. Immunoreactive IL-8 and TGF-beta in glomeruli was correlated with light microscopic and clinical features. There was a significant association (P < 0.05), between IL-8 glomerular immunoreactivity and neutrophil infiltration and between TGF-beta glomerular staining and mesangial matrix expansion. Otherwise, there was no correlation with the mesangial cellularity. It was concluded that increased protein expression of IL-8 and TGF-beta are observed in APSGN and may play a role in the acute glomerular inflammation.
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PMID:Immunohistochemical localization of IL-8 and TGF-beta in streptococcal glomerulonephritis. 904 42

Although interleukin (IL)-8 is well known as a chemotactic agent for neutrophil migration in vitro, the relationship between IL-8 activity and the degree of neutrophil infiltration in gastric mucosa is still unclear. In the present study, we investigated IL-8 and myeloperoxidase activity, a marker of neutrophil infiltration, in gastric antral mucosa using biopsy samples in 23 patients with no gastric lesions. The results indicate that there is a good correlation between IL-8 and myeloperoxidase activity (y = 0.173x + 13.9; r = 0.49, P < 0.01). Furthermore, IL-8 and myeloperoxidase activity are significantly higher in Helicobacter pylori-positive patients than in H. pylori-negative patients. In conclusion, an increase of IL-8 activity in the gastric mucosa causes increased neutrophil infiltration in human gastric mucosa and H. pylori infection accelerates these reactions in the mucosa.
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PMID:Relationship between interleukin-8 levels and myeloperoxidase activity in human gastric mucosa. 908 10

Neutrophil infiltration is a major feature in the pathogenesis of the common cold, and respiratory viral infection is the major cause of asthma exacerbations. The factors regulating the neutrophil influx are unknown. Interleukin-8 (IL-8) is a potent neutrophil chemoattractant, which has been implicated in several inflammatory diseases. In this study, we investigated the presence of IL-8 chemokine in the nasal aspirates of asthmatic children (n = 12) in whom asthma was precipitated by proven viral infection. There were increased IL-8 levels in nasal aspirates from children during the virus-induced asthma exacerbations compared with samples from the same children when they had been asymptomatic for 2 wk (medians 863 and < 20 pg/ml, respectively, p < 0.01). Biological relevance was shown in that IL-8 levels correlate with increased nasal aspirate neutrophil myeloperoxidase levels and there was also a correlation between myeloperoxidase levels and upper respiratory symptom severity. Furthermore, we purified IL-8 from these samples, and demonstrated biological neutrophil chemotactic activity. These are the first in vivo data to suggest an important role for IL-8 in neutrophil influx in proven upper respiratory viral infection associated with asthma exacerbations. We suggest that IL-8 might provide a target for therapeutic intervention in virus-induced respiratory diseases.
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PMID:Role of nasal interleukin-8 in neutrophil recruitment and activation in children with virus-induced asthma. 910 80

The C-X-C chemokines of the IL-8 family possess potent chemotactic activity for neutrophils, but their in vivo role in inflammatory responses is not well understood. In the IgG immune complex-induced model of acute lung inflammatory injury in the rat we have evaluated the roles of two rat chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC). Both mRNA and protein for MIP-2 and CINC appeared in a time-dependent manner after initiation of IgG immune complex deposition in lung. There exists a 69% homology between the amino acid sequences for these proteins, and we found cross-reactivity between polyclonal Abs raised to these chemokines. By purifying the blocking Abs using double affinity methods (with Ag-immobilized beads), this cross-reactivity was removed. Individually, anti-MIP-2 and anti-CINC Ab significantly reduced lung injury (as measured by 125I-labeled albumin leakage from the pulmonary vasculature) and reduced neutrophil accumulation in the lung (as determined by myeloperoxidase (MPO content) and neutrophil counts in bronchoalveolar lavage (BAL) fluids); however, no change in TNF-alpha levels in BAL fluids was found. Chemotactic activity in BAL fluids collected 2 h after injury from animals undergoing immune complex deposition could be shown to be chiefly due to the combined contributions of MIP-2 (39%), CINC (28%), and C5a (21%). When either MIP-2 or CINC was blocked in vivo, up-regulation of Mac-1 expression on neutrophils obtained from BAL fluids was significantly reduced. These data suggest that, in the model studied, both MIP-2 and CINC contribute significantly to the influx of neutrophils and their activation.
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PMID:Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury. 912 Mar 5

Although circulating levels of interleukin 8 (IL-8), a potent pro-inflammatory chemokine, and many other inflammatory mediators increase in response to cardiopulmonary bypass, only a small proportion of patients develop a clinically significant systemic inflammatory response. The natural mechanisms that control the inflammatory response are poorly understood. To investigate the role of IL-8 in a human inflammatory model, 15 adult patients undergoing cardiopulmonary bypass for elective coronary artery bypass grafting were studied. Following reperfusion, plasma IL-8 levels increased significantly from 58 pg/mL (pre-bypass) and 66 pg/mL (after 20 min of bypass) to 98 pg/mL (p = .02 and .04, respectively), but this was accompanied by a concomitant threefold decrease in the IL-8 binding affinity of circulating neutrophils (Dissociation constant (KL) post-reperfusion/KL pre-bypass = 3.2; KL post-reperfusion/KL after 20 min of bypass = 2.8). IL-8-triggered release of myeloperoxidase and elastase by peripheral blood neutrophils ex vivo was also down-regulated following reperfusion. There were no significant changes in beta 2 integrin expression or inositol polyphosphate metabolism of peripheral blood neutrophils. These changes in receptor affinity and neutrophil responsiveness to IL-8 may represent an important in vivo regulatory mechanism which serves to prevent excessive tissue injury from inflammatory triggers.
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PMID:Desensitization of the inflammatory response in humans: changes in response to cardiopulmonary bypass. 937 61

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