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)

To understand how neutrophils are recruited to the lung in pneumococcal pneumonia, the ability of pneumococcal components to elicit the chemokine interleukin (IL)-8 from monolayers of cultured human type II cells was assessed. Heat-killed clinical and laboratory strains of Streptococcus pneumoniae and secreted proteins from exponentially growing pneumococci elicited significant quantities of IL-8 from A549 cells. All strains that elicited IL-8 production secreted a protein ( approximately 90 kDa) that comigrated on SDS-PAGE with a C3-binding protein previously identified in S. pneumoniae. As little as 7 pmol of the purified 90-kDa protein readily elicited levels of IL-8 production equivalent to those obtained with 1 U of IL-1alpha. Supernatant proteins and heat-killed cells of an isogenic mutant that failed to produce the C3-binding protein elicited significantly less IL-8 than did supernatant proteins or heat-killed cells of the parent strain. These results implicate the C3-binding protein of S. pneumoniae in a novel pathway of pulmonary inflammation.
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PMID:A pneumococcal protein that elicits interleukin-8 from pulmonary epithelial cells. 1076 64

Sulfite exposure can induce inflammatory responses characterized by an influx of neutrophils into the airways leading to lung malfunctions. Studies focusing on sodium sulfite (Na(2)SO(3))/neutrophil interactions have shown that this chemical possesses proinflammatory properties based on its ability to induce a respiratory burst. Information regarding how this chemical could alter other neutrophil responses/functions as well as its role on immature promyelocytic cells is currently lacking in the literature. In this study, we report that Na(2)SO(3) can induce tyrosine phosphorylation events in human neutrophils but not in both HL-60 and HL-60 + DMSO. As a positive control, GM-CSF was found to induce tyrosine phosphorylation of a particular protein of 120-130 kDa in both HL-60 and HL-60 + DMSO cells testifying that these cells were responsive. In addition, we report that Na(2)SO(3) does not alter neutrophil phagocytosis and that this chemical increases the release of the proinflammatory cytokine IL-8 but not TNF-alpha. Paradoxically, we found that Na(2)SO(3) acts as a potent inhibitor of de novo neutrophil protein synthesis in a concentration-dependent fashion (0.1, 1, or 10 mM) as assessed by SDS-PAGE from metabolically [(35)S]-labeled cells. In contrast to mature neutrophils, we found that Na(2)SO(3) does not modulate de novo protein synthesis in HL-60 cells treated with low concentrations (0. 1 or 1 mM) and that this pollutant was toxic at 10 mM as judged by a drastic decrease of total protein content stained with Coomassie blue. We conclude that Na(2)SO(3) can activate human neutrophils and that its proinflammatory potential is further supported by its ability to increase IL-8 production. In addition, our results clearly indicate that HL-60 and HL-60 + DMSO respond differently than mature human neutrophils to the inflammatory pollutant Na(2)SO(3). Extrapolation of data obtained with HL-60 (and/or HL-60 + DMSO) to neutrophils should be taken with caution. Our data obtained with Na(2)SO(3) are an example.
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PMID:Activation of human neutrophils by the air pollutant sodium sulfite (Na(2)SO(3)): comparison with immature promyelocytic HL-60 and DMSO-differentiated HL-60 cells reveals that Na(2)SO(3) is a neutrophil but not a HL-60 cell agonist. 1090 Jan 60

This study investigated whether soluble paracrine factors mediated Salmonella-induced IL-8 expression in polarized model intestinal epithelia. We found that the basolateral media of model epithelia that had been apically infected with Salmonella typhimurium for a short period (10 minutes) could activate IL-8 secretion in virgin model epithelia, demonstrating that a proinflammatory factor (PIF) was indeed present. Initial characterization found that PIF was a heat-stable protein with a molecular mass of about 50 kDa that acts on the basolateral, but not apical, surface of model intestinal epithelia to elicit IL-8 secretion. PIF was not present in the media of model epithelia stimulated with other inducers of IL-8 secretion (TNF-alpha or carbachol) but was present in S. typhimurium supernatants, indicating PIF is of bacterial origin. PIF was purified from bacterial culture supernatants by anion/cation exchange chromatography and SDS-PAGE and found by using microsequencing to be the protein flagellin. In support of this finding, flagellin-deficient S. typhimurium mutants did not secrete detectable levels of PIF (i.e., a bioactivity that induced IL-8 secretion when placed basolaterally on model epithelia). Furthermore, viable flagellin-deficient mutant organisms (fliC/fljB and flhD) failed to elicit IL-8 secretion when added apically to model intestinal epithelia. These findings indicate that translocation of flagellin across epithelia, subsequent to apical epithelial-S. typhimurium interaction, is likely a major means of activating a mucosal inflammatory response.
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PMID:Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. 1113 75

Feline peripheral blood mononuclear cells (PBMC)-derived chemotactic factor induced by egg white derivatives (EWD) treatment was analyzed at the protein and messenger ribonucleic acid (mRNA) level. EWD itself was not active chemotactic for feline peripheral blood polymorphonuclear cells (PMN). But chemotaxis of PMN was enhanced by either culture supernatant from PBMC treated with EWD or human recombinant (hr) interleukin (IL)-8. Both hr IL-8 and the culture supernatant from PBMC treated with EWD yielded a distinct band, molecular weight of 6-8kDa, in sodium-dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with 15% loading gel. Therefore, to identify this chemotactic factor, culture supernatant from PBMC treated with EWD was partially purified by anion exchange chromatography on diethylaminoethyl (DEAE)-Sepharose CL-6B and concentrated by ultrafiltration. Only the fraction, which was eluted with 0.3M NaCl, showed a high concentration of total protein and also enhanced the chemotactic activity of PMN. This activity was thereafter designated as eluate. The chemotactic activity of eluate was inhibited by anti-hr IL-8 polyclonal antibody (pAb). A single protein band with 6-8kDa was shown in both the eluate and hr IL-8 when analyzed by SDS-PAGE and Western blotting using anti-hr IL-8 pAb, suggesting that the chemotactic factor for feline PMN is IL-8, 6-8kDa, produced by PBMC treated with EWD. The physicochemical characteristics of eluate were stable in heated (60-100 degrees C), acid (pH 3.0), and alkaline (pH 9.0) conditions. The eluate under these conditions also showed a distinct band in molecular weight of 6-8kDa in SDS-PAGE and Western blotting and was very active in chemotactic activity of PMN.IL-8 mRNA gene expression on feline PBMC was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) assay using a series of oligonucleotides, each 22 mer, derived from feline IL-8. Feline IL-8 mRNA showed low level in 3-h incubation without EWD, but it was increased in a dose-dependent manner by addition of EWD. Following EWD (10 microg/ml) treatment, IL-8 mRNA expression was rapidly increased up to 6h and decreased by 12h although it was not expressed in freshly prepared PBMC. This study strongly suggested that immunoenhancing effect of EWD on chemotactic response of PMN is mediated by feline IL-8, 6-8kDa, produced by PBMC stimulated with EWD. In addition, the expression of feline IL-8 mRNA on PBMC is increased when stimulated with EWD.
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PMID:Feline interleukin-8 expression in peripheral blood mononuclear cells induced by egg white derivatives. 1194 29

Although intravenous immunoglobulins (IVIG) and other plasma therapeutics have had a relatively good safety record, improved methods for viral clearance are constantly being evaluated and incorporated into new manufacturing processes. Gamma irradiation has been used routinely to assure sterility of healthcare products and medical devices, but it has not been applied successfully as a viral inactivation method for biologics. We examine whether virucidal doses of gamma irradiation (50 kGy) can be delivered to a manufacturing intermediate form of IVIG, a fractionated plasma paste, with negligible effect on structural and functional integrity of purified IgG product. Immunoglobulins from paste were examined for radiation-induced damage by SDS-PAGE and ELISAs utilizing viral antigens specific for rubella, CMV and mumps. Fc domain integrity was assessed by immunoblotting, quantitatively comparing the binding of irradiated and non-irradiated materials to cell surface Fcgamma receptors, and by employing quantitative RT-PCR to study the kinetics of accumulation of mRNA for the immune modulatory cytokines IL-1alpha, IL-1beta, IL-4, IL-8, IFNgamma, and TNFalpha. The results demonstrate that Fab and Fc domains of IVIG remain essentially intact and functional after gamma irradiation to virucidal doses, suggesting that this method could be used to enhance the safety of IVIG products.
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PMID:Functional integrity of intravenous immunoglobulin following irradiation with a virucidal dose of gamma radiation. 1545 88

The outer membrane proteins of Moraxella catarrhalis, a bacterial pathogen which causes disease in both children and adults, play an important role in its phenotypic properties. However, their proinflammatory potential with regard to respiratory epithelium and macrophages is unclear. To this end, we examined the cytokine- and mediator-inducing capacity of a heat-killed wild-type M. catarrhalis strain and a nonautoagglutinating mutant as well as their outer membrane proteins and secretory/excretory products using the A549 respiratory epithelial cell line. The outer membrane proteins and secretory/excretory products from both isolates as well as the heat-killed bacteria all induced interleukin (IL)-6, IL-8 and prostaglandin E2, but not IL-1beta, from the A549 cell line in a dose- and time-dependent manner. Heat-killed bacteria and secretory/excretory products stimulated the release of IL-1beta, IL-6, IL-8 and prostaglandin E2 from human monocyte-derived macrophages. Both heat-killed isolates also stimulated nuclear translocation and transactivation of nuclear factor-kappaB. The heat-killed wild-type autoagglutinating isolate induced significantly greater amounts of IL-6 and IL-8 from A549 cells than the nonautoagglutinating mutant compared with the monocyte-derived macrophages but no significant differences in the amounts induced by the two strains were observed. These differences were also evident when the respiratory cell line was stimulated with outer membrane proteins as well as in the degree of nuclear factor-kappaB transactivation. There was little difference in the stimulatory activity of the secretory/excretory products. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analyses revealed some differences in the outer membrane proteins and secretory excretory products between the two isolates. Combined, these data show that M. catarrhalis secretory excretory products and outer membrane proteins are associated with the induction of inflammatory responses in both respiratory epithelium and macrophages.
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PMID:Moraxella catarrhalis stimulates the release of proinflammatory cytokines and prostaglandin E from human respiratory epithelial cells and monocyte-derived macrophages. 1648 1

We showed recently that contact of human vaginal epithelial cells (VECs) by Trichomonas vaginalis and incubation with trichomonad proteins in conditioned medium induced expression of VEC genes. We performed 2-D SDS-PAGE followed by MALDI-TOF to identify the major secreted proteins. Based on protein abundance and separation of spots in 2-D gels, 32 major secreted proteins were examined, which gave 19 proteins with accession numbers. These proteins included known secreted cysteine proteinases. In addition, other secreted proteins were enzymes of carbohydrate metabolism, adhesin protein AP65, heat shock proteins, thioredoxin reductase and coronins. We confirmed that the secreted trichomonad proteins induced expression of VEC genes, including interleukin 8 (IL-8), COX-2 and fibronectin. Purified AP65 added to VECs had a pronounced effect only on IL-8 gene expression, which was inhibited in the presence of 12G4 monoclonal antibody to AP65. Moreover, AP65 expressed episomally within epithelial cells was found to enhance the expression of IL-8 and COX-2. This may be the first report of analysis of the secreted proteins of T. vaginalis and of the host epithelial cell response to these proteins and to the prominent adhesin AP65.
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PMID:The proteins secreted by Trichomonas vaginalis and vaginal epithelial cell response to secreted and episomally expressed AP65. 1759 Jan 65

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequently diagnosed cancers. It is believed that tumor production of various immune suppressive mediators contributes to massively impaired immune functions, but the underlying signal transduction pathways are mostly unknown. Phosphorylation levels of MAP (mitogen-activated protein) kinase p38 were analyzed in permanent cell lines as well as in solid tumor tissue of HNSCC using flow cytometry and SDS-PAGE. Cytokine secretion was determined using the Cytometric Bead Array Flex Set system. MAP kinase p38 was shown to be activated in HNSCC by phorbol 12-myristate 13-acetate. Activation of p38 led to decreased cell proliferation and increased secretion of cytokines IL-6 and IL-8 in HNSCC. Our data provide novel insights into the origin of the HNSCC microenvironment. A better understanding of these molecular mechanisms in HNSCC is essential for novel drug development and improvement of the clinical perspective of this tumor type.
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PMID:Increased cytokine secretion in head and neck cancer upon p38 mitogen-activated protein kinase activation. 1798 98

The mitochondrial anti-viral signaling protein (MAVS), also known as CARDIF, IPS-1, KIAA1271 and VISA, is a mitochondria associated protein that regulates type I interferon production through coordinated activation of NF-kappaB and IRF3. The N-terminal CARD domain of MAVS interacts with RIGI helicase of upcapped RNA detection and the putative TRAF2 and TRAF6 binding motifs modulate protein interaction for NF-kappaB activation. MAVS is encoded by a single gene composed of 6 exons but is generally detected as multiple protein bands after separation by SDS-PAGE. In an effort to identify MAVS variants with diverse biological functions, we isolated three splicing variants and named them MAVS 1a (exon 2 deletion), 1b (exon 3 deletion) and 1c (exon 6 deletion), respectively. MAVS 1a and 1b, due to a frame shift by exon deletion, encode 131 and 124 aa residues, respectively. Except the first 39 aa residues encoded by exon 1, MAVS 1a does not share sequence homology with known proteins, it instead contains a putative TRAF2-binding motif and interacts with TRAF2 and RIP1. MAVS 1b shares the first 97 residues with wt MAVS and 27 aa residues of unknown protein. Unlike MAVS that activates both NF-kappaB and IRF3 pathways, expression of MAVS 1b selectively activates an IFNbeta but not an IL8 promoter. MAVS 1b interacts with RIP1 and FADD and exhibits anti-viral activity against VSV infection. This study uncovers MAVS splicing variants of diverse biological function.
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PMID:Identification of MAVS splicing variants that interfere with RIGI/MAVS pathway signaling. 1820 45

Dendritic cells (DCs), efficient-antigen presenting cells play an important role in initiating and regulating immune responses. DC maturation following exposure to nickel or DNCB induced an up-regulation of phenotypic markers and inflammatory cytokine secretion. Early intracellular mechanisms involved in DC maturation required to be precise. To address this purpose, DCs derived from human monocytes were treated with sensitizers (nickel, DNCB or thimerosal) in comparison with an irritant (SDS). Our data confirming the up-regulation of CD86, CD54 and cytokine secretion (IL-8 and TNFalpha) induced by sensitizers but not by SDS, signalling transduction involved in DC maturation was investigated using these chemicals. Kinase activity measurement was assessed using two new sensitive procedures (Facetrade mark and CBA) requiring few cells. SDS did not induce changes in signalling pathways whereas NiSO(4), DNCB and thimerosal markedly activated p38 MAPK and JNK, in contrast Erk1/2 phosphorylation was completely inhibited by DNCB or thimerosal and only activated by nickel. A pre-treatment with p38 MAPK inhibitor (SB203580) suppressed Erk1/2 inhibition induced by DNCB or thimerosal demonstrating a direct interaction between p38 MAPK and Erk1/2. A pre-treatment with an antioxidant, N-acetyl-L-cysteine (NAC) markedly reduced Erk1/2 inhibition and p38 MAPK phosphorylation induced by DNCB and thimerosal, suggesting a direct activation of p38 MAPK via an oxidative stress and a regulation of MAPK signalling pathways depending on chemicals. Because of a high sensitivity of kinase activity measurements, these procedures will be suitable for weak or moderate sensitizer screening.
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PMID:Characterization of early events involved in human dendritic cell maturation induced by sensitizers: cross talk between MAPK signalling pathways. 1849 91


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