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)

The NaCl content of airway surface fluid is believed to be of central importance in lung pathology. To test whether the Na+ concentration could influence the inflammatory response in human bronchial epithelial cells (BECs), we investigated the interleukin (IL)-8 and RANTES expression in BECs exposed to an isotonic sea-water derived low Na+ (ISW) saline compared to isotonic 0.9% NaCl saline. Exposure of BECs to ISW saline caused a significant decrease in IL-8 and RANTES gene expression and protein production as compared to that observed with 0.9% NaCl saline. Furthermore, we observed a concomitant reduction of phosphorylated IkappaBalpha associated with a marked inhibition of NF-kappaB-DNA binding activity in BECs exposed to ISW saline as compared to 0.9% NaCl saline. These findings support a new role for Na+ in the pathogenesis of airway inflammatory disorders. Therapies targeted at lowering Na+ level in airway epithelium may be beneficial in treating inflammatory lung diseases.
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PMID:Reduction of chemokine IL-8 and RANTES expression in human bronchial epithelial cells by a sea-water derived saline through inhibited nuclear factor-kappaB activation. 1295 Oct 51

Permissive hypercapnia because of reduced tidal volume is associated with improved survival in lung injury, whereas therapeutic hypercapnia-deliberate elevation of arterial Pco2-protects against in vivo reperfusion injury and injury produced by severe lung stretch. No published studies to date have examined the effects of CO2 on in vivo models of neonatal lung injury. We used an established in vivo rabbit model of surfactant depletion to investigate whether therapeutic hypercapnia would improve oxygenation and protect against ventilator-induced lung injury. Animals were randomized to injurious (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O) or protective ventilatory strategy (tidal volume, 5 mL/kg; positive end-expiratory pressure, 12.5 cm H2O), and to receive either control conditions or therapeutic hypercapnia (fraction of inspired CO2, 0.12). Oxygenation (alveolar-arterial O2 difference, arterial Po2), lung injury (alveolar-capillary protein leak, impairment of static compliance), and selected bronchoalveolar lavage and plasma cytokines (IL-8, growth-related oncogene, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha) were measured. Injurious ventilation resulted in a large alveolar-arterial O2 gradient, elevated peak airway pressure, increased protein leak, and impaired lung compliance. Therapeutic hypercapnia did not affect any of these outcomes. Tumor necrosis factor-alpha was not increased by mechanical stretch in any of the groups. Therapeutic hypercapnia abolished the stretch-induced increase in bronchoalveolar lavage monocyte chemoattractant protein-1, but did not affect any of the other mediators studied. Therapeutic hypercapnia may attenuate the impairment in oxygenation and inhibit certain cytokines. Because hypercapnia inhibits certain cytokines but does not alter lung injury, the pathogenic role of these cytokines in lung injury is questionable.
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PMID:Therapeutic hypercapnia is not protective in the in vivo surfactant-depleted rabbit lung. 1456 81

Exposure to ambient air pollution particles causes greater health effects in individuals with preexisting inflammatory lung diseases. To model inflammatory priming in vitro, HTB54 lung epithelial cells were pretreated with tumor necrosis factor-alpha (TNF-alpha) and then exposed to a panel of environmental particles, including concentrated ambient particles (CAPs). TNF-alpha priming significantly enhanced interleukin (IL)-8 secretion in response to CAPs and other urban air particles in HTB54 cells. Enhancement was seen with whole CAP suspensions as well as with its separate water-soluble and -insoluble components. Treating CAP suspensions with 20 microM deferoxamine or 2 mM dimethylthiourea attenuated the enhancement, indicating that transition metals and oxidative stress participate in the CAPs-dependent IL-8 response of primed cells. Because activated neutrophils are also present in diseased lungs and are sources of additional oxidative stress on epithelial cells, primed HTB54 cells were cocultured with activated neutrophils. Wild-type neutrophils markedly enhanced IL-8 release to CAPs in primed HTB54 cells, an effect substantially diminished when neutrophils from NADPH knockout mice were used. Cytokine priming and interactions with activated neutrophils can amplify lung epithelial inflammatory responses to ambient air particles.
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PMID:Particle-epithelial interaction: effect of priming and bystander neutrophils on interleukin-8 release. 1463 Jun 11

Dichloroacetic acid (DCA) is a drinking water contaminant, a therapeutic agent, and a rodent carcinogen. Glutathione transferase zeta (GSTZ1-1) catalyzes the biotransformation of a range of alpha-haloalkanoates and the cis-trans isomerization of maleylacetoacetate. GSTZ1-1 catalyzes the bioactivation of fluorine-lacking dihaloacetates to S-(alpha-halocarboxymethyl)glutathione, a reactive intermediate that covalently modifies and inactivates the enzyme or is hydrolyzed to glyoxylate. The purpose of this study was to examine the GSTZ1-1-catalyzed bioactivation of DCA, including the reaction of DCA-derived glyoxylate with amino acid nucleophiles and the characterization of the structures and kinetics of adduct formation by LC/MS. The binding of [1-(14)C]DCA-derived label to bovine serum albumin required both GSTZ1-1 and GSH, whereas the binding to dialyzed rat liver cytosolic protein was increased in the presence of GSH. Studies with model peptides (antiflammin-2 and IL-8 inhibitor) indicated that glyoxylate, rather than S-(alpha-chlorocarboxymethyl)glutathione, was the reactive species that modified amino acid nucleophiles. Both addition (+74 Da) and addition-elimination (+56 Da) adducts of glyoxylic acid were observed. Addition adducts (+74 Da) could not be characterized completely by mass spectrometry, whereas addition-elimination adducts (+56 Da) were characterized as 2-carboxy-4-imidazolidinones. 2-Carboxy-4-imidazolidinones were formed by the rapid equilibrium reaction of glyoxylate with the N-terminal amino group of antiflammin-2 to give an intermediate carbinolamine (K(eq) = 0.63 mM(-1)), which slowly eliminated water to give an intermediate imine (k(2) = 0.067 hour(-1)), which rapidly cyclized to give the 2-carboxy-4-imidazolidinone. Glucose 6-phosphate dehydrogenase was inactivated partially by glyoxylate when reactants were reduced with sodium borodeuteride, which may indicate that glyoxylate reacts with selective lysine epsilon-amino groups. The results of the present study demonstrate that GSTZ1-1 catalyzes the bioactivation of DCA to the reactive metabolite glyoxylate. The reaction of glyoxylate with cellular macromolecules may be associated with the multiorgan toxicity of DCA.
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PMID:Glutathione transferase zeta-catalyzed bioactivation of dichloroacetic acid: reaction of glyoxylate with amino acid nucleophiles. 1514 22

Dendrimers are hyperbranched macromolecules that can be chemically synthesized to have precise structural characteristics. We used anionic, polyamidoamine, generation 3.5 dendrimers to make novel water-soluble conjugates of D(+)-glucosamine and D(+)-glucosamine 6-sulfate with immuno-modulatory and antiangiogenic properties respectively. Dendrimer glucosamine inhibited Toll-like receptor 4-mediated lipopolysaccharide induced synthesis of pro-inflammatory chemokines (MIP-1 alpha, MIP-1 beta, IL-8) and cytokines (TNF-alpha, IL-1 beta, IL-6) from human dendritic cells and macrophages but allowed upregulation of the costimulatory molecules CD25, CD80, CD83 and CD86. Dendrimer glucosamine 6-sulfate blocked fibroblast growth factor-2 mediated endothelial cell proliferation and neoangiogenesis in human Matrigel and placental angiogenesis assays. When dendrimer glucosamine and dendrimer glucosamine 6-sulfate were used together in a validated and clinically relevant rabbit model of scar tissue formation after glaucoma filtration surgery, they increased the long-term success of the surgery from 30% to 80% (P = 0.029). We conclude that synthetically engineered macromolecules such as the dendrimers described here can be tailored to have defined immuno-modulatory and antiangiogenic properties, and they can be used synergistically to prevent scar tissue formation.
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PMID:Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation. 1525 95

Mast cells are known to play an active role as effector cells in allergic inflammation and in diverse immunological and pathological processes. Activated mast cell-derived pro-inflammatory cytokines are important pathologic factors of progression of allergic inflammation. In this study, we investigated whether pro-inflammatory cytokines (TNF-alpha and IL-8) can be induced by calcium stimulation in HMC-1 cells, and high molecular weight water-soluble chitosan (WSC) can inhibit the production of these cytokines. We provided evidence that the secretion of TNF-alpha and IL-8 from HMC-1 cells was induced by Ca2+-ionophore A23187 or Ca2+-ATPase inhibitor TSG. Treatment of WSC (10 microg/ml) prior to stimulation with calcium agonists significantly blocked the secretion of TNF-alpha by 65.1% for A23187 and 87.7% for TSG. IL-8 secretion in response to A23187 or TSG was inhibited by 49.2% for A23187 and 34.1% for TSG, respectively, compared to absence of WSC. These results suggest that WSC has potential regulatory effects on allergic inflammatory diseases by down-modulating Ca2+-induced mast cell activation.
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PMID:Inhibitory effect of water-soluble chitosan on TNF-alpha and IL-8 secretion from HMC-1 cells. 1551 73

Acute respiratory distress syndrome (ARDS) in newborns and young infants is linked with an inflammatory response of the lungs which affects the capillary-alveolar permeability, epithelial integrity and type I and II pneumocyte function. Abundant extravascular lung water with a high protein content inactivates surfactant together with the enzymatic action of polymorphonuclear leukocytes (PMNL). We asked if a decrease in extravascular lung water and a reduction in lung infiltration with PMNL could be achieved by surfactant administration (Curosurf) within 6 h of mechanical ventilation when given in a newborn piglet model of repeated airway lavage. Improvements in gas exchange and lung mechanics were predominantly caused by resorption of extravascular lung water rather than by the reopening of alveolar atelectases. PMNL were significantly reduced in the bronchoalveolar lavage fluid after 6 h of mechanical ventilation. However, acute phase cytokines (IL-6, TNF-alpha) remained unchanged, except for IL-8 which increased after administration of surfactant. We conclude that the decrease in extravascular lung water and in infiltration with PMNL following surfactant administration is accomplished within 6 h through mechanisms different from attenuation of pro-inflammatory cytokines. Surfactant treatment for newborn and infant ARDS might therefore improve fluid overload and atelectasis and reduce PMNL infiltration.
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PMID:Surfactant reduces extravascular lung water and invasion of polymorphonuclear leukocytes into the lung in a piglet model of airway lavage. 1564 55

Oral treponemes are well-known as causative agents of periodontal diseases; however, the details have not been fully clarified. Here, we examined the effects of Treponema medium glycoconjugate on the activation of human gingival fibroblasts using phenol-water extracts from Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum subsp. nucleatum, and Actinobacillus actinomycetemcomitans. The phenol-water extracts activated human gingival fibroblasts to mediate IL-8 production, as well as IL-8 mRNA expression, phosphorylation of p38 mitogen-activated protein kinase, and expression of intercellular adhesion molecule-1. T. medium glycoconjugate exhibited no activation of human gingival fibroblasts, while phenol-water extract-induced activation of human gingival fibroblasts was clearly inhibited by T. medium glycoconjugate. Furthermore, binding of biotinylated phenol-water extracts to CD14 in the presence of LPS-binding protein was blocked with T. medium glycoconjugate. These results suggest that T. medium glycoconjugate has an inhibitory effect on host cell activation by periodontopathic bacteria caused by binding to CD14- and LPS-binding protein.
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PMID:Treponema medium glycoconjugate inhibits activation of human gingival fibroblasts stimulated with phenol-water extracts of periodontopathic bacteria. 1584 Jul 83

In acute liver failure (ALF), detoxification capacity of liver cells is reduced and a variety of cytokines, immune modulators, and toxic substances are accumulating. Multiple organ failure in ALF has been associated with increased blood cytokine levels. We have used a blood purification system, molecular adsorbent recirculating system (MARS), which is based on removal of both protein bound and water-soluble substances and toxins in liver failure. In this study, we measured the effect of MARS therapy on plasma cytokine levels in 49 patients with ALF. Interleukin 6 (IL-6), IL-8, IL-10 and tumor necrosis factor (TNF)alfa were determined immediately before and after the first MARS therapy and after the last session using enzyme-linked immunosorbent assays. The overall survival of these ALF patients was 82% at 6 months; the native liver recovered in 26 cases, and 14 were successfully transplanted. All three interleukins were increased before the MARS treatment but only anti-inflammatory IL-10 was reduced significantly during therapy, which in this setting could be interpreted as a positive effect. We were not able to show constant decreases in proinflammatory cytokines, but only transient effects on IL-8 and IL-6. Surprisingly TNFalfa level was normal and did not change during therapy. In theory, MARS albumin dialysis may remove toxic substances from the blood circulation and thereby improve the possibilities of the liver to recover; however, of the measured cytokines only IL-10 decreased significantly.
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PMID:The effect of albumin dialysis on cytokine levels in acute liver failure and need for liver transplantation. 1584 31

Adjuvants induce the expression of a number of genes in dendritic cells (DCs), which facilitate effective antigen-presentation and cytokine/chemokine liberation. It has been accepted that the toll-like receptor (TLR) family governs the adjuvant activity in DCs. An adjuvant with a long history is mycobacteria in an oil-in-water emulsion, namely Freund's complete adjuvant. Since the active center for the adjuvancy in mycobacteria is the cell-wall skeleton (CWS), we used the bacillus Calmette-Guerin cell-wall skeleton (BCG-CWS) to test DC maturation by GeneChip analysis. We identified the genes supporting an efficient DC response and output. Approximately 2000 genes were up-regulated by BCG-CWS stimulation. BCG-CWS-, peptidoglycan (PGN)- and lipopolysaccharide (LPS)-stimulation generally up-regulated some gene clusters including genes for inflammatory cytokines (TNF, IL1alpha, IL1beta, IL6, IL12 p40, IL23 p19, etc.), chemokines (CCL20, IL8, etc.), cell adhesion molecules (ICAM-1, etc.), apoptosis-related proteins (GADD45B, BCL2A1, etc.), metabolic enzymes (PTGS2, SOD2, etc.) and miscellaneous proteins (EHD1, TNFAIP6, etc.). LPS-stimulation, but not BCG-CWS- or PGN-stimulation, up-regulated the interferon-inducible antiviral proteins, including IFIT1, IFIT2, IFIT4, CXCL10, ISG15, OASL, IFITM1 and MX1. We also found that the BCG-CWS- or PGN-stimulation up-regulated CXCL5, MMP1, etc. We discussed their properties in association with TLRs and recently discovered TLR adapters.
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PMID:Gene-inducing program of human dendritic cells in response to BCG cell-wall skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy. 1586 Feb 29


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