Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-8 (IL-8) priming was studied in neutrophils to examine its dependency on altered calcium fluxes and for similarity to lipopolysaccharide (LPS). IL-8 caused a rapid rise in [Ca2+]i that returned to baseline values by 20 min. Peak [Ca2+]i transients in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) were unaltered in IL-8-primed compared with unprimed cells. In comparison to LPS and tumor necrosis factor (TNF), IL-8 was a much weaker priming agent as measured by either O2- or H2O2 production. Despite their large disparity in potency, IL-8 and LPS printing were additive using fMLP, a receptor-dependent stimulator, and synergistic using the post-receptor, protein kinase C activator, phorbol 12-myristate 13-acetate (PMA) to trigger the respiratory burst. In contrast, IL-8 and TNF priming were synergistic for fMLP (P = 0.05), but completely nonadditive when PMA was used as the neutrophil stimulant (P = 0.05 for subadditivity). Thus, lasting alterations in [Ca2+]i are not a necessary characteristic of IL-8-primed cells. IL-8 and LPS appear to prime by non-overlapping pathways, whereas IL-8 and TNF appear to share mechanisms distal to protein kinase C activation. IL-8 and LPS may independently contribute to neutrophil-mediated host defense or injury by priming through distinct pathways.
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PMID:Interleukin-8 priming of human neutrophils is not associated with persistently altered calcium fluxes but is additive with lipopolysaccharide. 976 32

In addition to their damaging effects, reactive oxygen intermediates exert a regulatory role on gene expression and cell apoptosis. In this study, we evaluated the effects of oxidative stress on human dendritic cells (DC), a cell type which is critical for the initiation of the immune response. For this purpose, we tested the effects of H2O2 on DC derived from adherent peripheral blood mononuclear cells cultured in the presence of granulocyte-macrophage colony-stimulating factor and IL-4. Despite a moderate increase of DC apoptosis in the presence of H2O2, we observed that H2O2 stimulated the production of IL-8 and TFN-alpha by DC in a dose-dependent manner. The induction of cytokine synthesis was found to depend on the oxidative properties of H2O2 as it was inhibited by the addition of catalase, and to require de novo protein synthesis as it was not observed in the presence of cycloheximide. These data suggest that DC could contribute to innate immunity through an enhanced production of inflammatory cytokines in response to oxidative stress.
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PMID:Oxidative stress up-regulates IL-8 and TNF-alpha synthesis by human dendritic cells. 984 32

A direct correlation has been reported between the severity of symptoms associated with rhinovirus infection and the concentration of interleukin-8 in nasal secretions. The purpose of these studies was to examine the mechanism of rhinovirus-induced IL-8 elaboration. Rhinovirus infection induced oxidative stress in Beas-2b cells and the concentration of H2O2 in supernatant media from rhinovirus challenged cells was 12.5 +/- 6.1 microM 1 h after challenge compared to 0.7 +/- 0.3 microM in supernatant from control cells. N-acetyl cysteine inhibited RV-induced NF-kappaB activation and IL-8 elaboration. IL-8 concentrations were 36 +/- 2 pg/ml and 10 +/- 1 pg/ml 6 h after virus challenge in untreated and NAC-treated (30 mM NAC) cells, respectively. Despite the effects of NAC on IL-8 elaboration and NF-kappaB activation, RV stimulated increases in supernatant H2O2 were not altered by NAC. These data suggest that RV stimulation of IL-8 in respiratory epithelium is mediated through production of oxidative species and the subsequent activation of NF-kappaB.
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PMID:The role of oxidative stress in rhinovirus induced elaboration of IL-8 by respiratory epithelial cells. 989 38

The promoters of the IL-8, MCP-1, and RANTES genes contain binding sites for the redox-responsive transcription factors AP-1 and NF-kappaB, which have been shown to be important for their expression. In this overview, we present evidence from our laboratories that the stimulus-specific regulation of these chemokines by the reactive oxidant H2O2, the proinflammatory cytokine TNF-alpha, and respiratory syncytial virus (RSV) is mediated in a cell type-specific manner involving different patterns of AP-1 and NF-kappaB binding activity. Our results demonstrate that H2O2 induction of IL-8 gene expression is linked with the selective binding of AP-1 to the IL-8 promoter, whereas TNF-alpha and RSV induction of IL-8 correlates with the activation of NF-kappaB binding. We propose that the differential activation and binding of inducible transcription factors to the promoter regions of chemokine genes provides a critical regulatory mechanism by which the CXC and CC chemokines can be selectively expressed in a cell type-specific and stimulus-specific manner. Such a regulatory mechanism of differential chemokine expression could critically influence the site-specific recruitment of distinct subsets of leukocytes to sites of inflammation and injury.
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PMID:Stimulus-specific regulation of chemokine expression involves differential activation of the redox-responsive transcription factors AP-1 and NF-kappaB. 1008 May 30

The lung is susceptive to excess oxidants from inhaled air and marginated large portion of circulating leukocytes. Oxygen radicals generated from sequestrated leukocytes injure endothelial cells to increase permeability. Excessively generated oxidants in the mitochondria, such as in ischemia-reperfusion injury, changes mitochondrial function and cause Ca++ leak from the organelle, which leads to induction of apoptosis. Reactive oxygen intermediates induce some cytokine gene expression such as IL-8. Hydrogen peroxide activates phospholipase C and the subsequent signal transduction pathways resulting in change of cytoskeletal configuration and cell shape. It is expected that understanding of contribution of oxidant-antioxidant imbalance in lung diseases may develop new strategy of 'antioxidant' therapies.
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PMID:[Lung tissue injury caused by oxidant-antioxidant imbalance]. 1049 95

We used flow cytometry to analyze the expression of adhesion molecules and the oxidative burst of whole-blood polymorphonuclear neutrophils (PMN) from 26 patients with periodontitis. Three different clinical entities were studied: adult periodontitis (AP), localized juvenile periodontitis (LJP), and rapidly progressive periodontitis (RPP). Unstimulated PMN from the patients showed reduced Lewis x, sialyl-Lewis x, and L-selectin expression relative to those from healthy control subjects. These alterations were present whatever the severity of periodontal disease. However, PMN from RPP patients showed increased basal H2O2 production and decreased L-selectin shedding. These latter impairments, which correlated with increased IL-8 plasma levels, could contribute to initial vascular damage. In addition, decreased IL-8 priming of H2O2 production by PMN from RPP patients could account for a lower bactericidal capacity of PMN, leading to the large number of bacteria in the subgingival region of RPP patients. Soluble L-selectin plasma levels were also decreased in the RPP group, indicating more severe or diffuse endothelial damage. These abnormalities were not found in the patients with less destructive forms of periodontitis (AP and LJP). Porphyromonas gingivalis, a bacterial pathogen known to increase IL-8 production by PMN, was found in the periodontal pockets of RPP patients only. These results show links among PMN abnormalities, the clinical form of periodontitis, and the gingival bacterial flora.
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PMID:Neutrophil dysfunctions, IL-8, and soluble L-selectin plasma levels in rapidly progressive versus adult and localized juvenile periodontitis: variations according to disease severity and microbial flora. 1052 6

Macrolides have therapeutic benefits on chronic inflammatory airway diseases. Thus, macrolides are supposed to have variable biological effects apart from antimicrobial activity. Neutrophil adherence and influx with oxidants and cytokines production implicates involvement in airway inflammation. To investigate whether erythromycin (EM) affects neutrophil activity in vitro, lipopolysaccharide (LPS)-treated neutrophils were continuously incubated for 4 h in the absence or presence of increasing doses of EM from 1 microg ml(-1) to 100 microg ml(-1) in the last 2 h. Leukocyte adhesion molecules Mac-1 and intracellular H2O2(DCFH) were determined by flowcytometric assay. IL-8 and TNFalpha in supernatant was measured by ELISA method. The expression of Mac-1 and mean intracellular DCF fluorescence intensity (DCFH) of neutrophils significantly increased after stimulation with LPS. Pretreatment with EM significantly decreased LPS induced Mac-1 expression on neutrophils compared with LPS stimulation only. EM alone (100 microg ml(-1)) also decreased Mac-1 expression on neutrophils. EM significantly reduced the LPS-increased DCFH. EM alone (100 microg ml(-1)) also caused a decrease in DCFH. Increasing doses of EM also significantly decreased the IL-8 released by LPS-stimulated neutrophils. In conclusion, EM exerts a direct effect on the neutrophils by downregulating the expression of beta2-integrin on neutrophils, thus leading to a decrease in the intracellular H2O2, as well as the production of IL-8. Our conclusion provides an explanation for the clinical efficacy of erythromycin in neutrophil-mediated airway inflammation.
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PMID:Erythromycin inhibits beta2-integrins (CD11b/CD18) expression, interleukin-8 release and intracellular oxidative metabolism in neutrophils. 1092 36

The skin protects our body by producing an efficient barrier membrane, the stratum corneum, from desiccation as well as from various damaging effects of environmental chemicals. Although the skin expresses various cytokines after barrier perturbation, exact cell types producing each cytokine have not been determined. Using a cell culture system, we analyzed the initial responses of various cutaneous cells to treatments simulating epicutaneous stimuli induced by a barrier perturbation of the skin in comparison with those caused by irritant or hapten exposure. We used cultured normal human epidermal keratinocytes (NHEK), human microvascular endothelial cells (HMVEC) and normal human dermal fibroblasts (NHDF). We treated them with the following chemicals and examined their cytokine mRNA levels 6 h later: high osmotic (0.5 molar) NaCl and hydrogen peroxide (H2O2), which simulate desiccation and exposure to high oxygen pressure, respectively, that may take place in vivo after perturbation of the barrier. In addition, we also studied their response to two representive haptens, nickel chloride (NiCl2) and dinitrochlorobenzene (DNCB), and an irritant, sodium dodecyl sulfate (SDS). We found that 0.5 M NaCl treatment increased mRNA levels of proinflammatory cytokines such as IL-1alpha, IL-6 and IL-8 as well as ICAM-1 in NHEK and IL-1alpha, IL-1beta and IL-6 mRNA levels in NHDF. In contrast, H2O2 treatment remarkably increased IL-10, GMCSF and ICAM-1 mRNA levels in NHEK, and IL-6 mRNA levels in HMVEC and NHDF. The exposure to haptens did not induce any remarkable increase in mRNA levels of the proinflammatory cytokines in NHEK. But NiCl2 increased IL-1alpha, IL-6 and IL-8 mRNA levels in HMVEC, while DNCB increased only their IL-6 mRNA levels. By contrast, SDS stimulated all the cell types to increase at least some of these proinflammatory cytokine mRNA levels. Our present data suggest that each skin component cell participates in inflammatory processes of the skin through its distinctive cytokine production profile when the skin barrier is compromized physically or chemically.
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PMID:Cytokine mRNA profiles in cultured human skin component cells exposed to various chemicals: a simulation model of epicutaneous stimuli induced by skin barrier perturbation in comparison with that due to exposure to haptens or irritant. 1137 23

We have documented the time-dependent production of chemotactic cytokine, i.e., IL-8, in the extracellular fluid of astrocyte-rich cultured rat cerebellar granule cells under acidified conditions. In this paper, the mechanism of this production was evaluated based on the production of hydrogen peroxide (H2O2). Significant and time-dependent increases of cytosolic H2O2 were detected under acidosis in astrocyte-rich cultured cell. Upon exposure to 10 microM H2O2, significant levels of IL-8 appeared in the extracellular fluid of astrocyte-rich cells, although an initial transient increase of IL-8 was also seen in the intracellular space. Concurrently, after H2O2 exposure cell injury and a delayed increase of cytosolic Ca2+ levels were detected in astrocyte-rich cells. However, in the absence of extracellular Ca2+, the cell injury and the increase of IL-8 production were significantly attenuated. A synergistic effect of cyclosporine A (an inhibitor of the Ca2+/calmodulin-regulated protein phosphatase) and trifluoperazine (an inhibitor of phospholipase A2) on the suppression of H2O2-induced IL-8 production was clearly evident. These results suggest that extracellular acidosis induced Ca2+-dependent H2O2 production, which in turn stimulated IL-8 expression. which is regulated by the cytosolic Ca2+ cascade. Thus, the production of IL-8 from glia cells may have a role in regulating in the process of cell injury.
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PMID:Hydrogen peroxide induced chemokine production in the glia-rich cultured cerebellar granule cells under acidosis. 1183 44

Epidemiological and animal studies have indicated that consumption of green tea and high vitamin E intake are associated with a reduced risk of developing certain forms of cancer. However, the inhibitory mechanism of green tea catechins and vitamin E in angiogenesis, an important process in tumor growth, has not been well established. In the present study, alpha-tocopherol and several major catechins of green tea (catechin, epicatechin, epicatechin gallate, epigallocatechin, and epigallocatechin gallate) were tested for their ability to inhibit tube formation in vitro using a model in which human microvascular endothelial cells were exposed to a constant rate of a physiologically low level of H2O2. In this model, the production of interleukin (IL)-8 by human microvascular endothelial cells at a low level of H2O2 was required for angiogenesis, as assessed by tube formation in three-dimensional gel in culture. Vitamin E (d-alpha-tocopherol, 40 microM) in the culture media significantly reduced IL-8 production and angiogenesis. Among the green tea catechins, epigallocatechin (0.5-1 microM) was the most effective in reducing IL-8 production and inhibiting angiogenesis. These results suggest that consumption of green tea catechins or supplemental intake of vitamin E may have preventive effects on tumor development, mediated, at least in part, through inhibition of angiogenesis via suppression of IL-8 production.
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PMID:Green tea catechins and vitamin E inhibit angiogenesis of human microvascular endothelial cells through suppression of IL-8 production. 1209 14


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