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)

It was shown previously that leukoregulin (LR), a T cell-derived cytokine with unique antitumor properties, modulates fibroblast functions in vitro, including prostaglandin production, matrix synthesis, and protease gene expression. Here, we have focused on the ability of LR to modulate IL-8 gene expression in human dermal fibroblasts. Using a specific ELISA, we demonstrated a dose-dependent enhancement of IL-8 production by LR, accompanied by a parallel elevation of the corresponding mRNA levels, as measured by Northern hybridizations. Maximum accumulation of IL-8 mRNA was observed after 6 h of incubation with LR, and the elevation persisted over 24 h. Inhibition of protein synthesis by cycloheximide resulted in superinduction of IL-8 mRNAs by LR. Dexamethasone, all-trans-retinoic acid, and TGF-beta 1 failed to counteract the effect of LR on IL-8 gene expression. Transient cell transfections with an IL-8 promoter/CAT reporter gene construct showed a dose-dependent enhancement of the promoter activity by LR, suggesting transcriptional regulation. Gel shift assays with oligonucleotides containing the consensus NF-kappa B binding sequences of the IL-8 and Ig kappa light chain genes showed enhanced binding activity in nuclear extracts from cells incubated with LR. Transient transfection experiments using a NF-kappa B/SV2 promoter-CAT reporter gene construct showed enhanced CAT activity by LR. Taken together, these data suggest that LR may up-regulate IL-8 gene expression by activation of the binding of NF-kappa B to the corresponding cis-acting element in the IL-8 promoter. Our results demonstrate that LR, together with IL-1 and TNF-alpha, could participate in the recruitment of neutrophils to the sites of inflammation by induction of IL-8 production in fibroblasts.
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PMID:Leukoregulin, a T cell-derived cytokine, induces IL-8 gene expression and secretion in human skin fibroblasts. Demonstration and secretion in human skin fibroblasts. Demonstration of enhanced NF-kappa B binding and NF-kappa B-driven promoter activity. 140 24

IL-8 is produced by a wide variety of cells in response to polyclonal mitogens and cytokines. Northern blotting analysis revealed that IL-1, TNF and PMA could induce rapid expression of IL-8 mRNA in the absence of new protein synthesis. Nuclear run-off assays using different cell types demonstrated that IL-8 mRNA expression could at least be partly due to the activation of transcription. Cloning and determination of the entire sequence of IL-8 genomic DNA enabled us to explore the functional significance of the 5'-flanking enhancer region of the IL-8 gene by employing CAT assays. The results indicated that the region spanning from -94 to -71 bp is minimally sufficient for conferring responsiveness to IL-1, TNF and PMA. Further analysis using point-mutations revealed that this region consisted of two distinct cis-elements; one being the potential binding site for NFkB-like and the other for a C/EBP-like factor. These results suggested that all three stimuli, IL-1/TNF/PMA, modulate the identical combination of nuclear factors possibly by phosphorylation. We previously reported that these three stimuli activated the same serine protein kinase which phosphorylates identical 65 kDa and 74 kDa cytosol proteins in human PBMC. This IL-1/TNF/PMA-activated protein kinase is distinct from protein kinase A, protein kinase C or casein kinase in substrate specificity; in Ca and phospholipid dependency; in cyclic nucleotide dependency; and sensitivity to protein kinase inhibitors. Taken collectively, IL-1/TNF/PMA may activate a common serine protein kinase and this protein kinase may in turn directly or indirectly modulate several nuclear factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of human interleukin 8 gene expression and binding of several other members of the intercrine family to receptors for interleukin-8. 175 77

During the chemotactic migration of human neutrophilic granulocytes towards the chemotactic factors f-Met-Leu-Phe, C5a, leukotriene B4 (LTB4), monocyte-derived chemotaxin (MOC/IL-8) and platelet-activating factor (PAF) in Boyden chambers, the production of superoxide anion and hydrogen peroxide was measured by superoxide dismutase-inhibitable cytochrome C reduction and oxidation of p-OH-phenylacetic acid, respectively. With the exception of 10(-6) M PAF, none of the factors at optimal chemotactic concentrations induced the production of O2- or H2O2 in amounts significantly different from neutrophilic granulocytes migrating at random. At 20-50 times the optimal chemotactic concentration some O2- and H2O2 production was observed with f-Met-Leu-Phe, C5a and LTB4, but not with MOC/IL-8. Superoxide dismutase, catalase or a combination of the two added to both compartments of the Boyden chambers did not affect the random or chemotactic migration towards any of the chemotactic factors. The results suggest that chemotactic migration and the production of reactive oxygen metabolites by human neutrophilic granulocytes are unrelated events.
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PMID:Production of superoxide anion and hydrogen peroxide by human neutrophilic granulocytes during chemotactic migration towards f-Met-Leu-Phe, C5a, leukotriene B4, monocyte-derived chemotaxin/IL-8 and platelet-activating factor. 196 31

The aim of this study was to determine whether polymorphonuclear neutrophils (PMN) can modify the immune response in HIV cases. Supernatants of PMN (PMNS) from 33 HIV-infected patients (16 with lymphoadenopathy syndrome, 17 with AIDS-related complex) were tested for their influence on the functional activity of lymphocytes and monocytes from 6 healthy donors. PMNS from another 6 healthy donors comprised a control group. It was found that PMNS from HIV-infected patients, but not from healthy donors, induced suppression of lymphocyte proliferative response and down-regulation of CD8 receptor expression on lymphocytes. Decrease of NK-cell cytotoxicity in the presence of PMNS from HIV-infected patients was the same as that from healthy donors. PMNS did not influence the production of anti-HIV antibody by lymphocytes from HIV-infected patients, as well as non-specific IgG by lymphocytes from healthy donors. PMNS effect on functional activity of lymphocytes was blocked completely after treatment of PMN by catalase and superoxide dismutase. At the same time PMNS from HIV-infected patients but not from healthy donors induced increased production of TNF-alpha by monocytes and up-regulation of monocyte phagocytosis. These effects were independent of catalase and superoxide dismutase and were not abrogated by antibody against IL-1, IL-8, TNF-alpha, IFN-gamma or IFN-alpha.
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PMID:Modification of lymphocyte and monocyte functional activity by polymorphonuclear neutrophils in HIV infection. 846 29

Two distinct receptors for the neutrophil chemoattractant IL-8 have been cloned, designated IL-8RA and -B. Both receptors are abundantly expressed on unstimulated mature neutrophils. To understand the tissue-specific expression and to identify gene-regulatory elements we have cloned, sequenced and characterized both human IL-8R genes, IL-8RA and -B. The open reading frames and 3'-untranslated regions were entirely encoded by a single exon. The promoters of both IL-8R-genes appeared to be very similar: A non-classical TATA-box and a GC-rich 5'-flanking region was identified immediately upstream of the transcription start site. These minimal promoters were sufficient to generate constitutive activity in CAT-expression assays. A G-CSF responsive element was mapped within the first 118 nucleotides upstream of the transcription start site of the IL-8RB gene. Expression analyses of additional upstream regions suggested that both IL-8R-promoters are negatively controlled by silencer elements, which could be counteracted by stimulation with G-CSF.
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PMID:Promoter analysis of the human interleukin-8 receptor genes, IL-8RA and IL-8RB. 853 Jan 63

To understand the pathogenesis of vasculitides, we analyzed how cytokine stimulation of HUVEC in vitro activates the cytotoxic capacity of polymorphonuclear (PMN) granulocytes. IL-1beta, IFN-gamma, or TNF-alpha caused highly significant dose and time-dependent HUVEC injury. TNF-alpha-treated HUVEC activated the PMN by means of phospholipase C-related event, since coincubations conferred PMN to react with a rise of cytosolic calcium concentrations, [Ca2+]i. Ab blockade of ICAM-1 on HUVEC inhibited 50 to 70% of the injury induced by these cytokines, whereas a mAb to E-selectin reduced 45 to 65% of IL-1beta- and TNF-alpha-, but not IFN-gamma-induced cytotoxicity. The role of nitric oxide (NO) was of significance since injury induced by each cytokine was reduced by 60 to 87% by specific NO-synthase inhibitors, as well as by scavenging extracellular NO by oxyhemoglobin. In contrast, injury induced by TNF-alpha was inhibited by neither superoxide dismutase or catalase, alpha1-antitrypsin, alpha2-macroglobulin, nor the platelet-activating factor receptor antagonist WEB-2086. Moreover, PMN from a patient with chronic granulomatous disease were fully capable of mediating cytotoxicity. The possibility that IL-8, produced by HUVEC in response to TNF-alpha, mediated activation of PMN was not corroborated since addition of an IL-8-blocking mAb did not modify HUVEC injury. Nonetheless, the IL-8 mAb (but not WEB-2086) blocked the rise of [Ca2+]i. Thus, in this in vitro model of vasculitis, the effect of IL-1beta, IFN-gamma, and TNF-alpha as promotors of cytokine-mediated neutrophil-dependent injury to HUVEC is a process dependent on expression of adhesion molecules and probably associated with NO produced in the system.
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PMID:Cytokine-induced neutrophil-mediated injury of human endothelial cells. 921 11

The aim of the present study was to determine the efficacy of a new combination regimen including an antioxidant, a proton pump inhibitor, and antibiotics against Helicobacter pylori and to document the changes of oxidative stress and cytokines involved in H. pylori-associated gastric inflammation. From 57 patients with endoscopically diagnosed gastric and/or duodenal ulcers associated with H. pylori infection five gastric antral biopsy specimens were taken for the diagnosis of H. pylori and for the experimental measures. The patients were then treated either with lansoprazole 30 mg + amoxicillin 1.5 g (LA group; 21 patients) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg (LAM group; 36 patients) for two weeks. Four weeks after the initiation of treatment, the patients were endoscoped again and biopsy specimens were obtained. Mucosal malondialdehyde (MDA) levels; myeloperoxidase (MPO) activities; superoxide dismutase; catalase; glutathione peroxidase; cytokines IL-1, IL-6, TNF-alpha; and chemokines IL-8, GRO-alpha, RANTES (regulated on activation normal T expressed and secreted) were measured. Using paraffin-embedded tissue sections, in situ terminal deoxyribonucleotide transferase (TdT) mediated dUTP nick end labeling (TUNEL) for apoptosis and immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Two weeks of treatment with the LA regimen resulted in 57.4% eradication rates of H. pylori, whereas two weeks of treatment with the LAM regimen resulted in 75.0% eradication rates. Eradication rates between these two groups were statistically significantly different (P < 0.05). Mucosal MDA levels and MPO activities were significantly lower in the LAM group than the LA group. Mucosal levels of cytokines IL-1, IL-6, and TNF-alpha and of chemokines IL-8, GRO-alpha, and RANTES were all significantly decreased after the treatment of H. pylori, especially so in the LAM group. The apoptotic index and iNOS score were significantly reduced after the eradication of H. pylori. The addition of an antioxidative drug to the eradication regimen against H. pylori has advantages either in augmenting the eradication rates of H. pylori or in decreasing the oxidative stress and cytokines levels generated by H. pylori infection.
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PMID:Augmented eradication rates of Helicobacter pylori by new combination therapy with lansoprazole, amoxicillin, and rebamipide. 951 12

Inflammatory mediators, including cytokines and chemokines, are associated with the pathology of chronic liver disease. Interleukin-8 (IL-8) in humans and macrophage inflammatory protein-2 (MIP-2) in rodents, both members of the C-X-C family of chemokines, are particularly potent neutrophil attractants and have been implicated in chronic liver diseases. In the liver, cytokine secretion is usually associated with non-parenchymal cells, particularly Kupffer cells. In the present studies, chemokine gene expression and secretion were investigated in hepatocytes treated with various stimulators. Using human Hep G2 cells, it was demonstrated that, in contrast to lipopolysaccharides (LPS), both tumor necrosis factor-alpha (TNF-beta) and H2O2 are potent inducers of IL-8, presumably acting via protein kinase C (PKC)-dependent pathways. MIP-2 expression occurred in freshly isolated rat hepatocytes following treatment with TNF-alpha, LPS, and to a lesser degree, H2O2. Both IL-8 and MIP-2 secretion were inhibited, although to varying degrees, by such antioxidants as TMTU, DMSO, catalase, and N-acetylcysteine. Furthermore, in vitro TNF-alpha neutralization experiments and transfection of Hep G2 cells with an IL-8 construct confirmed that TNF-alpha and H2O2 directly stimulate IL-8 secretion. RT-PCR analyses indicated that chemokine secretion induced by these agents operates via increased gene expression. Furthermore, a variety of cytokine genes were found to be expressed by hepatocytes, including MCP-1, cytokine-induced neutrophil chemoattractant (CINC), and IL-6. Taken together, these studies indicate that hepatocytes respond to biologically relevant levels of common activators, including H2O2, to produce cytokines and chemokines that contribute to pathophysiologic and repair processes in the liver.
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PMID:Cytokine expression in hepatocytes: role of oxidant stress. 972 45

Intracellular metabolism of chromium(VI) [Cr(VI)] may lead to oxidative stress and this may account for the ability of Cr(VI) to act as a complete carcinogen. Therefore, we examined the effects of Cr(VI) treatment on the expression of oxidative stress genes in normal human lung LL 24 cells and human lung adenocarcinoma A549 cells. RT-PCR and northern blot analyses were used to determine the steady-state mRNA levels of catalase, glutathione S-transferase, glutathione reductase, Cu/Zn- and Mn-superoxide dismutases, glutathione peroxidase, NAD(P)H:quinone oxidoreductase, heme oxygenase and interleukin 8 in control cells and cells treated with 5-200 microM of Cr(VI). We found that only expression of the heme oxygenase gene is strongly elevated under the treatment with Cr(VI), and only in normal human lung LL 24 cells. Our data showed that even in the absence of Cr(VI) treatment, the level of heme oxygenase gene expression is much higher in A549 cells than in LL 24 cells. As glutathione is believed to play a protective role in cells against different forms of oxidative stress, we studied the correlation between intracellular glutathione levels and the inducibility of the heme oxygenase gene after treatment of cells with Cr(VI). Our results demonstrate that glutathione levels are increased by 35 % of control values in LL 24 cells treated with Cr(VI). The data obtained indicate that heme oxygenase, known to be a stress-inducible gene, may be involved in cellular pathways critical to the carcinogenic activity of Cr(VI) in normal human lung cells. Intracellular glutathione levels and reactive oxygen species do not appear to be primarily responsible for the stress response, induced by Cr(VI) in the studied human cells.
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PMID:Effects of Cr(VI) on the expression of the oxidative stress genes in human lung cells. 974 36

The aim of the present study was to determine the efficacy of a new combination regimen including antioxidant, proton pump inhibitor, and antibiotics against Helicobacter pylori and to document the changes of oxidative stress and cytokines involved in H. pylori-associated gastritis. From each of 57 patients with endoscopically diagnosed gastric and/or duodenal ulcers associated with H. pylori infection, five gastric antral biopsy specimens were taken for the diagnosis of H. pylori and for experimental measures. The patients were then treated either with lansoprozole 30 mg + amoxicillin 1.5 g (LA group; 21 patients) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg (LAM group; 36 patients) for two weeks. Four weeks after the initiation of treatment, the patients were endoscoped again and biopsy specimens were obtained. Mucosal malondialdehyde (MDA) levels; myeloperoxidase (MPO) activities; superoxide dismutase; catalase; glutathione peroxidase; cytokines IL-1, IL-6, TNF-alpha; and chemokines IL-8, GRO-alpha, RANTES (regulated on activation normal T expressed and secreted) were measured. Using paraffin-embedded tissue sections, in situ terminal deoxyribonucleotide transferase (TdT) -mediated dUTP nick end labeling (TUNEL) for apoptosis and immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Two weeks of treatment with the LA regimen resulted in 57.4% eradication rates of H. pylori, whereas two weeks of treatment with the LAM regimen resulted in 75.0% eradication rates. Eradication rates between these two groups were statistically significantly different (P < 0.05). Mucosal MDA levels and MPO activities were significantly lower in the LAM group than the LA group. Mucosal levels of cytokines IL-1, IL-6, and TNF-alpha and of chemokines IL-8, GRO-alpha, and RANTES were all significantly decreased after the treatment of H. pylori, especially in the LAM-treated group. The apoptotic index and iNOS score were significantly reduced after the eradication of H. pylori. The addition of the antioxidative drug rebamipide to the eradication regimen against H. pylori has quantitative and qualitative advantages such as either augmenting the eradication rates of H. pylori or decreasing oxidative stress and cytokines levels generated by H. pylori infection.
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PMID:Quantitative and qualitative usefulness of rebamipide in eradication regimen of Helicobacter pylori. 975 49


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