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)

DNA binding activity of NF-kappa B and AP-1 were examined in neutrophils stimulated with LPS purified from P. gingivalis, a major pathogenic bacteria of periodontitis lesion. Porphyromonas gingivalis LPS enhanced the activity reaching a peak at a concentration of 500 ng/ml in the absence of serum. The NF-kappa B activation stimulated with 10 ng/ml of P. gingivalis LPS was suppressed approximately 44% by treatment of neutrophils with anti-CD14 antibody under the presence of serum. Increase in the steady-state IL-8 mRNA level was concomitantly observed by stimulation of neutrophils with 500 ng/ml of P. gingivalis LPS under the absence of serum. These results indicate that P. gingivalis LPS activates NF-kappa B and AP-1 in both serum-dependent and -independent manners, followed by increased IL-8 transcription in neutrophils, and suggested a role for P. gingivalis LPS in IL-8 synthesis by neutrophils in inflamed gingiva and GCF.
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PMID:Activation of transcription factors and IL-8 expression in neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis. 960 13

The observations that several types of viruses induced interleukin (IL)-8 production prompted us to investigate the interrelationship between IL-8 and cytomegalovirus (CMV) infection. CMV infection caused IL-8 production in a human monocytic cell line, THP-1, in dose- and time-dependent manners. Moreover, CMV induced IL-8 gene expression by concurrently activating transcription factors, NF-kappaB and AP-1. Furthermore, CMV infection of human fibroblast cell lines increased gene expression of a specific receptor for IL-8, CXCR1. IL-8 in turn enhanced CMV replication in a human embryonic fibroblast, MRC-5, in dose- and time-dependent manners. Augmented replication eventually culminated in the increased production of infectious CMV virions. Moreover, IL-8 can attenuate the antiviral activity of interferon (IFN), particularly that of alpha-type against picornaviruses such as encephalomyocarditis virus and poliovirus. The inhibitory effects were associated with reduced 2',5'-A oligoadenylate synthetase activity. These results would imply that CMV can induce IL-8, which can augment CMV replication directly and indirectly by counteracting antiviral activity of IFN.
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PMID:Potential involvement of IL-8 in the pathogenesis of human cytomegalovirus infection. 966 76

The health effect of atmospheric pollution is causing increasing public concern. Several controlled human-exposure studies have clearly. shown that oxidant pollutants, including ozone, nitrogen dioxide, and diesel exhaust, induce an acute inflammatory response in human airways. The main component of this response involves the influx of polymorphonuclear leukocytes (PMN) and is mediated via the upregulation of transcription factors NF-kappa B, AP-1, and NF-IL6; leukocyte-endothelial adhesion molecules, and chemokine secretion, including IL-8 and Gro-alpha. The results of recent studies also suggest that short-term exposure to ozone leads to neurogenic inflammation by causing damage to the bronchial epithelium and stimulating subepithelial sensory nerves to release substance P. In addition, such exposures lead to the consumption of endogenous antioxidants that are present in the airway lining fluid. Studies in asthmatics have shown that oxidant pollutants, including ozone and nitrogen dioxide, induce PMN influx in the airways and potentiate responses to inhaled aero-allergens. This article will review various studies addressing the toxicological mechanisms underlying oxidant pollutant-induced airways injury.
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PMID:Toxicological mechanisms underlying oxidant pollutant-induced airway injury. 971 22

The transactivator protein, Tax, from the human T-cell leukemia virus type I (HTLV-I) transactivates both viral and cellular genes. Previously, we had shown that interleukin 8 (IL-8) is constitutively expressed in HTLV-I-infected cells and in cells transiently expressing Tax. We show here that the IL-8 promoter is Tax responsive in Jurkat T cells. Furthermore, using several deletion and mutated plasmids of the 5'-flanking regulatory region of the IL-8 gene linked to the luciferase gene as a reporter and mutant tax gene expression vectors, we have established that both AP-1 at -126 to -120 and nuclear factor (NF)-kappaB-like cis-element at -80 to -71 are essential and sufficient for the induction of the IL-8 gene by HTLV-I Tax. In addition, overexpression of the dominant-negative mutants of NF-kappaB inhibitor molecules, IkappaBalpha and IkappaBbeta, abolished the Tax-induced activation of IL-8 gene. Gel mobility shift assays detected proteins specifically binding to the AP-1 and NF-kappaB-like sites in Tax-expressing T-cell lines infected with HTLV-I. Similarly, the nuclear translocation of proteins specifically bound to these two motifs was shown in JPX-9 cells, a subclone of Jurkat cells, carrying the Tax sequences under the control of an inducible promoter. Taken together, these results suggest that the cooperation of transcription factors NF-kappaB and AP-1 is essential for transactivation of IL-8 gene by HTLV-I Tax.
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PMID:Human T-cell leukemia virus type I Tax transactivates human interleukin 8 gene through acting concurrently on AP-1 and nuclear factor-kappaB-like sites. 973 13

Interleukin-8 (IL-8) may play an important role in Helicobacter pylori infection-associated chronic active gastritis and peptic ulcer disease in human. We have recently reported that a gastric cancer cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori. Moreover, H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription. In this study, we evaluated the effect of rebamipide, an antigastritis and antiulcer agent, on H. pylori-induced IL-8 production. Rebamipide inhibited the production of IL-8 in several gastric cancer cell lines infected with H. pylori. In addition, rebamipide suppressed H. pylori-induced IL-8 gene expression at the transcriptional level as revealed by northern blotting analysis and luciferase activity in cells that were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44). Furthermore, rebamipide significantly suppressed the NF-kappaB activation by H. pylori infection. These results suggest that rebamipide may protect against the mucosal inflammation associated with H. pylori infection through inhibition of a proinflammatory cytokine, IL-8.
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PMID:Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori-stimulated gastric cancer cell lines. 975 46

Paclitaxel (Taxol) is a novel anti-cancer drug that has shown efficacy toward several malignant tumors, particularly ovarian tumors. We reported previously that paclitaxel can induce interleukin (IL)-8 promoter activation in subgroups of ovarian cancer through the activation of both AP-1 and nuclear factor kappaB. Further analysis of paclitaxel analogs indicates that the degree of IL-8 induction by analysis correlates with the extent of cell death; however, IL-8 itself is not the cause of cell death. This suggests that pathways that lead to IL-8 and cell death may overlap, although IL-8 per se does not kill tumor cells. To decipher the upstream signals for paclitaxel-induced transcriptional activation and cell death, we studied the involvement of protein kinases that lead to the activation of AP-1, specifically the c-Jun NH2-terminal kinase (JNK1), p38, and the extracellular signal-regulated kinase 1 (ERK1). The role of IkappaB in paclitaxel-induced cell death was also analyzed. Paclitaxel activated JNK, and to a lesser degree p38, but not ERK1. Paclitaxel-induced IL-8 promoter activation was inhibited by dominant-inhibitory mutants of JNK, p38, and the super-repressor form of IkappaBalpha, but not by dominant-inhibitory forms of ERK1. Dominant-inhibitory mutants of JNK1 also greatly reduced paclitaxel-induced cell death, and the kinetics of JNK induction was closely followed by DNA fragmentation. These results indicate (i) that paclitaxel activates the JNK signaling pathway and (ii) that JNK activation is a common point of paclitaxel-induced gene induction and cell death.
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PMID:Paclitaxel (Taxol)-induced gene expression and cell death are both mediated by the activation of c-Jun NH2-terminal kinase (JNK/SAPK). 977 47

Heavy metal ions can be released by corroding metallic implants into the surrounding tissue. When they enter blood vessels some of them are carried by proteins like albumin and can be taken up by endothelial cells lining the vessels. To study their involvement in the inflammatory response we investigated heavy metal ion induced effects in cultured human vascular endothelial cells (HUVECs). NiCl2 and CoCl2 upregulate, especially in concentrations of 1 mM, the expression of adhesion molecules (e.g., E-selectin and intercellular adhesion molecule-1), as well as the cytokines IL-6 and IL-8, as shown by enzyme immunoassay and Northern blot analysis. In addition, possible signal transduction mechanisms were elucidated. The HUVECs were treated with various selective inhibitory drugs followed by the incubation of metal ions before measuring the expression of the above-mentioned endothelial factors. Two protein kinase inhibitors (H-7 and H-8) strongly repressed Ni2+ and Co2+ enhanced expression, as did the phospholipase A2 inhibitor quinacrine. Other selective inhibitors of protein kinases C or A, or cGMP-dependent protein kinases, as well as calcium antagonists like 1,2-bis(2-aminophenoxy)ethan-N,N,N',N'-tetraacetic acid and 3,4,5-trimethoxybenzosaure 8-(diethylamino)-octylester and inhibitors of receptor mediated endocytosis (primary amines), had no influence. We showed that NiCl2 and CoCl2 activate the translocation of the transcription factor nuclear factor (NF)-kappaB into the cell nucleus and enhance its binding to a NF-kappaB consensus sequence as shown by mobility shift analysis. Furthermore, we demonstrated the activation of AP-1. Despite the repression of heavy metal induced adhesion molecule synthesis, we did not detect any inhibition of NF-kappaB translocation by H-7 or H-8. Therefore, it must be concluded that heavy metal ions like Ni2+ and Co2+ activate two or more signal transduction pathways in endothelial cells. We clearly showed that there is one pathway in which H-7 and H-8 sensitive protein kinases are involved and a second pathway leading to NF-kappaB activation, which is insensitive to H-7 and H-8. Our results demonstrate that heavy metal ions induce mechanisms of gene activation in endothelial cells as do proinflammatory mediators, indicating that corroding metal ion containing biomaterials can provoke inflammatory reactions by known, as well as by yet unknown, intracellular signaling pathways.
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PMID:Mechanisms of cell activation by heavy metal ions. 1088 Jan

Oxygen deprivation is an important biological feature of tumor growth. We previously showed that in glioma, anoxia increases expression of IL-8, a chemokine and angiogenic factor. Here, we analysed for the first time the biochemical mechanisms inducing the IL-8 gene upon anoxia in glioma cells, and showed that they differ from those inducing the VEGF gene. Both genes are induced in biologically and genetically heterogenous glioblastoma cell lines (LN-229, LN-Z308, U87MG, T98G), whereas, in gliosarcoma cells (D247MG), only the VEGF gene is induced. The kinetics of IL-8 and VEGF mRNA inductions differ in these cells and reoxygenation experiments showed that the induction is due to the anoxic stress per se. Furthermore, in LN-229 and LN-Z308 cell lines actinomycin D, DRB and nuclear run-on experiments showed that anoxia stimulates increased transcription of both genes. Electromobility shift assays show increased protein binding to the AP-1 site on the IL-8 promoter following anoxia treatment. Finally, in situ hybridization on glioblastoma sections shows that the in vivo expression patterns of IL-8 and VEGF genes overlap, but are not identical. Since intratumoral augmentation of IL-8 and VEGF secretion, following microenvironmental decreases in oxygen pressure, may promote angiogenesis, further definition of these pathways is essential to appropriately target them for antitumoral therapy.
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PMID:Regulation of interleukin-8 expression by reduced oxygen pressure in human glioblastoma. 1005 Aug 81

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

Extensively oxidized low density lipoprotein (ox-LDL), a modulator of atherogenesis, down-regulates the lipopolysaccharide (LPS)-induced activation of transcription factor NF-kappaB. We investigated whether 4-hydroxynonenal (HNE), a prominent aldehyde component of ox-LDL, represents one of the inhibitory substances. NF-kappaB activation by stimuli such as LPS, interleukin (IL)-1beta, and phorbol ester, but not tumor necrosis factor (TNF), was reversibly inhibited by HNE in a dose-dependent manner in human monocytic cells, whereas AP-1 binding was unaffected. Using similar HNE concentrations, LPS-induced kappaB- and TNF or IL-8 promoter-dependent transcription was prevented. Furthermore, pretreatment with HNE suppressed TNF production but not lactate dehydrogenase levels. Under these conditions the binding of LPS to monocytic cells was not significantly affected. However, induced proteolysis of the inhibitory proteins IkappaB-alpha, IkappaB-beta, and, at a later time point, IkappaB-epsilon was prevented. This is not due to inhibition of the proteasome, the major proteolytic activities of which remain unaffected, but rather to a specific prevention of the activation-dependent phosphorylation of IkappaB-alpha. This is the first report which demonstrates that HNE specifically inhibits the NF-kappaB/Rel system. Down-modulation of NF-kappaB-regulated gene expression may contribute at certain stages of atherosclerosis to low levels of chronic inflammation and may also be involved in other inflammatory/degenerative diseases.
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PMID:4-Hydroxynonenal prevents NF-kappaB activation and tumor necrosis factor expression by inhibiting IkappaB phosphorylation and subsequent proteolysis. 1020 70

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