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)

High concentrations of oxygen, indispensable for the treatment of severe hypoxemia from neonatal as well as adult respiratory distress syndrome, increase the risk of oxygen toxicity. Biochemical mechanisms are lipid peroxidation, protein sulfhydryl oxidation, enzyme inactivation, and DNA damage. Recent reports suggest that cytokines might be involved in free radical injury as well as in adaptive response to hyperoxic injury. However, actual signal transduction pathways involving cytokines have not yet been clarified. In this study we exposed cultured human umbilical vein endothelial cells (HUVECs) to either ambient air or 100% oxygen, and compared for the rate of DNA synthesis ([3H]thymidine uptake) at different time points up to 72 h. After exposing the cells to each treatment condition, we extracted RNA, constructed complementary DNA using reverse transcriptase, amplified the specific DNA segments of cytokines by polymerase chain reaction (PCR), and used the PCR products for gel electrophoresis to examine the bands which signified mRNA levels of corresponding cytokines. There was a significant decrease in the rate of DNA synthesis as early as 24 h. The mRNA expression of IL-1 beta and TNFa seemed less influenced by hyperoxia, while IL-8 and TGF beta showed marked increase in mRNA levels at 6 h of 100% oxygen exposure.
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PMID:Hyperoxia influences mRNA expression of cytokines in cultured human umbilical vein endothelial cells. 952 79

TNF-alpha is implicated in the initiation of cytokine cascades in various inflammatory settings. To assess the interactions of multiple cytokines at the level of inflammatory effector cells, we examined the effects of TNF-alpha on the expression of two IL-8Rs (CXCR1 and CXCR2) on polymorphonuclear leukocytes (PMNs). TNF-alpha decreased the surface expression of CXCR2 in a dose- and time-dependent manner. In contrast, CXCR1 expression was not affected by TNF-alpha. The release of CXCR2 into the supernatant of TNF-alpha-treated PMNs was detected by immunoblotting and immuno-slot-blot analyses, suggesting that the down-regulation of CXCR2 was caused mainly by shedding from the cell surface. The CXCR2 down-regulation was inhibited by PMSF and aprotinin, supporting the hypothesis that the shedding was mediated by serine protease(s). The intracellular Ca2+ mobilization and chemotaxis in response to IL-8 were suppressed by the pretreatment of PMNs with TNF-alpha, indicating that the decrease in CXCR2 was reflected in the decreased functional responses to IL-8. In contrast, the O2- release, which is mediated by CXCR1, was not suppressed by TNF-alpha. The treatment of whole blood with TNF-alpha also caused a significant reduction in CXCR2 and markedly suppressed intracellular Ca2+ mobilization and chemotaxis in response to IL-8, while enhancing the O2- release. These findings suggest that TNF-alpha down-regulates CXCR2 expression on PMNs and modulates IL-8-induced biologic responses, leading to the intravascular retention of PMNs with an enhanced production of reactive oxygen metabolites.
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PMID:Down-regulation of CXCR2 expression on human polymorphonuclear leukocytes by TNF-alpha. 957 58

Interleukin-8 (IL-8) is a peptide which induces not only chemotaxis of neutrophils but also the release of reactive oxygen metabolites from the neutrophils. There are few reports which clarify the relationships between IL-8 and mucosal infiltration of neutrophils or reactive oxygen metabolites produced by neutrophils in the colonic mucosa of ulcerative colitis (UC). Biopsy specimens of colonic mucosa obtained from 26 patients with active UC and 21 patients with inactive UC were studied in order to clarify the relationships among the inflammation factors in UC. Levels of IL-8 and myeloperoxidase in organ culture media of the biopsy specimens from active UC (measured by ELISA and EIA) were significantly higher than those from inactive UC and controls. Reactive oxygen metabolites of biopsy specimens in active UC (measured by luminol-dependent chemiluminescence) were also markedly increased compared to those in inactive UC and controls. The levels of IL-8 were closely correlated to luminol-dependent chemiluminescence or myeloperoxidase levels. However, the levels of IL-8 and myeloperoxidase did not correlate with the grades of activity on colonoendoscopic findings. These findings suggest that IL-8 may play a role in the pathophysiology of UC but it does not define the endoscopic activity grades of UC.
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PMID:Correlations between interleukin-8, and myeloperoxidase or luminol-dependent chemiluminescence in inflamed mucosa of ulcerative colitis. 961 52

Fine particles in the air have been associated with increased mortality and morbidity. Particulate air pollution is a complex mixture which varies by region and includes a number of components including residual oil fly ash (ROFA), a byproduct of power plant and industry fuel-oil combustion. Human airway epithelial cells exposed to ROFA release inflammatory cytokines including interleukin (IL)-6, IL-8, and tumor necrosis factor. Expression of these genes is dependent upon pretranscriptional binding of cis regulatory elements, including nuclear factor kappaB (NF-kappaB). To investigate the role of NF-kappaB in the particulate-induced IL-6 response, we exposed human airway epithelial cells (BEAS-2B) to ROFA in vitro. ROFA stimulated a time- and dose-dependent increase in IL-6 messenger RNA (mRNA), which was preceded by the activation of nuclear proteins binding to the NF-kappaB sequence motif in the IL-6 promoter. Transient transfection of BEAS-2B cells with the 5' promoter region of the IL-6 gene linked to a luciferase reporter gene confirmed that NF-kappaB binding is necessary for the transcription of IL-6 mRNA. The IL-6 response was inhibited by the metal chelator deferoxamine and the free radical scavenger N-acetyl-L-cysteine, suggesting that the activation of NF-kappaB may be mediated through reactive oxygen intermediates generated by transition metals found in ROFA. Activation of NF-kappaB may therefore be a critical first step in the inflammatory cascade following exposure to particles generated by oil combustion.
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PMID:Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-kappaB activation. 965 Nov 85

Accumulating data from a number of laboratories have recently indicated that the response of transcription factor NF-kappaB to alterations in the redox homeostasis of cells may play an important role in modulating immune function. The activation of NF-kappaB has been recognized to regulate a number of genes necessary for normal T cell responses including IL-2, IL-6, IL-8, and several T cell surface receptors. Diminished NF-kappaB activity has been shown to occur in T cells with aging, suggesting that impaired activation of NF-kappaB might occur during cellular senescence. In addition, aberrancies in NF-kappaB activity have been implicated in the immunopathogenesis of diseases involving immune or inflammatory processes such as atherosclerosis and HIV-1 infection. The role of H2O2 and other reactive oxygen species (ROS) as an integratory secondary messenger for divergent T cell signals has been complicated by the fact that various T cell lines and peripheral blood T cells differ markedly in the levels of NF-kappaB activation induced by oxidant stress. Additionally, proposed pathways of NF-kappaB activation have been based on indirect evidence provided by experiments which used antioxidants to inhibit active NF-kappaB formation. Further, complete activation of T cells requires at least two signals, one that stimulates an increase in intracellular calcium and one that stimulates enzymatic processes including kinases. Similarly, substantial evidence indicates that full activation of NF-kappaB requires dual signals. The ability of H2O2 or other ROS to induce T cell signals and functional responses by these two mechanisms is reviewed and the specific response of NF-kappaB to redox changes in T cells is examined. Data are also presented to suggest that the redox regulation in NF-kappaB activation may be relevant to immune-related diseases and to aging.
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PMID:Redox signals and NF-kappaB activation in T cells. 968 Jan 81

TNF is produced by monocytes/macrophages in response to endotoxin, which may lead to septic shock. TNF stimulates neutrophil adherence, degranulation, and superoxide production, but inhibits neutrophil migration. A mitigating anti-inflammatory effect can be experimentally induced in septic shock by TNF blockers, such as pentoxifylline, and is also suggested for treatment with hrG-CSF. With regard to the combination of pentoxifylline and hrG-CSF, the purpose of this investigation was to explore whether and in what way the effects of hrG-CSF and pentoxifylline interact with each other in neutrophils. To this end, we studied the effects of pentoxifylline on TNF- and G-CSF-induced modulation of neutrophil chemotaxis and O2 release. TNF and G-CSF decreased directed migration of neutrophils to FMLP or IL-8. High-dose pentoxifylline (1 mM) was able to counteract the effect of TNF but not that of G-CSF on neutrophil migration. In the presence of pentoxifylline, TNF and G-CSF were unable to stimulate respiratory burst. In contrast, pre-exposure of cells to pentoxifylline followed by washing increased the priming effect of TNF or hrG-CSF on neutrophil respiratory burst activity. The methylxanthine derivative by itself showed no effect on spontaneous and fMLP-stimulated O2 release by neutrophils. Stimulation of neutrophil respiratory burst by pentoxifylline may not be detectable in the presence of pentoxifylline due to its known oxygen-radical scavenging function. Results suggest that by blocking the inflammatory action of TNF on neutrophils, pentoxifylline may diminish endothelial cell damage caused by inhibited neutrophil chemotaxis. On the other hand, since transiently present pentoxifylline may enhance the respiratory burst activity of TNF- or hrG-CSF-primed neutrophils, concomitant administration of pentoxifylline and hrG-CSF to patients with SIRS/sepsis might diminish beneficial effects of the latter and additional deleterious effects might occur.
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PMID:Pentoxifylline differentially regulates migration and respiratory burst activity of the neutrophil. 970 61

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

Ozone is one of the most common air pollutants humans routinely inhale. We have previously shown that in vitro ozone exposure induces the DNA-binding activities of NF-kappaB and NF-IL6 as well as the expression of interleukin 8 in respiratory epithelial cells. In this study, we investigated intracellular signaling steps mediating ozone-induced inflammatory mediator release. A549 cells, a type II like alveolar epithelial cell line, were exposed in vitro to air or 0.1 ppm of ozone in the presence of several kinase inhibitors. Exposure to ozone increased interleukin 8 expression and transcription factor activities in a protein tyrosine kinase (PTK)-dependent and protein kinase A (PKA)-dependent, yet protein kinase C (PKC)-independent, manner. Furthermore, ozone-induced PTK and PKA activities but failed to induce PKC activity. In addition, our results suggest that ozone-induced PTK and PKA activities were reactive oxygen intermediate dependent and occurred in parallel, because specific inhibitors for PTK and PKA failed to block the other kinase's activity. These results indicate that PTK and PKA activities are early events in the signal transduction cascade mediating the ozone-induced activation of NF-kappaB and NF-IL6 as well as the release of interleukin 8.
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PMID:Induction of interleukin-8 by ozone is mediated by tyrosine kinase and protein kinase A, but not by protein kinase C. 976 28

Inflammatory response to Helicobacter pylori is characterized by infiltration of neutrophils, monocytes, and lymphocytes into the gastric mucosa. Interleukin-8 (IL-8), a prototype of the CXC-chemokine subfamily, may be a key modulator in inducing neutrophil migration and activation in H. pylori-infected gastric mucosa. IL-8 is produced by gastric epithelial cells in response to H. pylori infection, and IL-8 expression is induced by local production of proinflammatory cytokines and attachment of H. pylori organisms to the gastric epithelial cell surface. Multiple genes in the H. pylori cag pathogenicity island seem to be involved in inducing the epithelial IL-8 response to H. pylori attachment. Activation of the transcription factor, nuclear factor kappaB (NF-kappaB), is associated with this IL-8 response. Reactive oxygen intermediates whose production is increased in H. pylori-infected gastric mucosa may also modulate IL-8 expression in the gastric mucosa. Recent reports also suggest that the local production of CC-chemokines, another chemokine subfamily, is important in H. pylori-associated gastritis.
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PMID:Chemokine expression in Helicobacter pylori-infected gastric mucosa. 977 23

Inflammatory mediators include endotoxin (ETX), cytokines (interleukins [ILs], tumor necrosis factors [TNFs], and interferons), eicosanoids (prostaglandins and thromboxanes), reactive oxygen species (O2-, NO, and ONOO-), complements (C3 and C4), and stress hormones (catecholamine, cortisol, vasopressin, and growth hormone). These mediators work to maintain homeostasis under stressful conditions through a complex chain reaction or cascade that results in transient tissue damage known as the inflammatory response. The inflammatory response is decreased by a negative feedback system, which consists not only of the self-inhibitory action of ETX, TNF-alpha, IL-1, and IL-8, but also of the production of antiinflammatory mediators such as IL-4, -10, -11, and -13, TGF-beta, IL-Ra, and sTNFR. If excessive stress or a second attack of stress results in a higher level of inflammation-producing mediators than of inflammation-inhibiting mediators, tissue destruction occurs due to activation and infiltration of inflammatory cells or necrosis due to endothelial injury is seen, followed by disruption of homeostasis, organ dysfunction, and organ failure (multiple organ dysfunction syndrome [MODS] or multiple organ failure [MOF] induced by SIRS). In experimental liver dysfunction after 95% hepatectomy, massive apoptosis of hepatocytes is induced by prolonged hypercytokinemia, ONOO- production, decreased mitochondrial membrane potential of hepatocytes, and decreased Bc12 levels. On the other hand, if the antiinflammatory response is greater than the inflammatory response (CARS) a compromised state and refractory infection are seen, followed by progressive, irreversible organ dysfunction (MODS or MOF induced by CARS).
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PMID:[Inflammatory mediator and organ dysfunction syndrome]. 978 83


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