Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial infection of the pulp and root canal system leads to the recruitment of immunocompetent cells in the periapex and stimulates inflammatory cell responses to produce a variety of inflammatory mediators. Cytokines, reactive oxygen intermediates, and reactive nitrogen intermediates are frequently found at sites of acute inflammation. In this study, we measured the levels of interleukin (IL)-8 and nitric oxide (NO) in the periapical exudate (PE) from human periapical lesions and investigated the association of these mediators with the clinical symptoms of periapical periodontitis. PE samples were collected from root canals during routine endodontic treatments. The IL-8 concentration was measured by the enzyme-linked immunosorbent assay, and the NO level was measured as nitrite/nitrate concentration assayed by the Griess reaction. Detectable levels of IL-8 and nitrite/nitrate were found in 24 and 19 of 27 PE-samples, respectively. Although PE-IL-8 and nitrite/nitrate concentration showed a broad range, a significantly positive correlation was found between both mediators. Also, significantly higher IL-8 levels were found in PE from lesions that had painful symptoms at the sampling visit. However, there was no relationship between elevated NO levels and clinical symptoms. These results suggest that the up-regulation of IL-8 may have a critical role in the development of the symptoms of periapical disease.
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PMID:Production of interleukin-8 and nitric oxide in human periapical lesions. 1177 82

Staphylococcus aureus alpha-toxin is a pore-forming bacterial exotoxin that has been implicated as a significant virulence factor in human staphylococcal diseases. In primary cultures of rat pneumocyte type II cells and the human A549 alveolar epithelial cell line, purified alpha-toxin provoked rapid-onset phosphatidylinositol (PtdIns) hydrolysis as well as liberation of nitric oxide and the prostanoids PGE(2), PGI(2), and thromboxane A(2). In addition, sustained upregulation of proinflammatory interleukin (IL)-8 mRNA expression and protein secretion occurred. "Priming" with low-dose IL-1beta markedly enhanced the IL-8 response to alpha-toxin, which was then accompanied by IL-6 appearance. The cytokine response was blocked by the intracellular Ca(2+)-chelating reagent 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, the protein kinase C inhibitor bis-indolyl maleimide I, as well as two independent inhibitors of nuclear factor-kappaB activation, pyrrolidine dithiocarbamate and caffeic acid phenethyl ester. We conclude that alveolar epithelial cells are highly reactive target cells of staphylococcal alpha-toxin. alpha-Toxin pore-associated transmembrane Ca(2+) flux and PtdIns hydrolysis-related signaling with downstream activation of protein kinase C and nuclear translocation of nuclear factor-kappaB are suggested to represent important underlying mechanisms. Such reactivity of the alveolar epithelial cells may be relevant for pathogenic sequelae in staphylococcal lung disease.
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PMID:Mediator generation and signaling events in alveolar epithelial cells attacked by S. aureus alpha-toxin. 1179 25

The effect of inhaled nitric oxide (NO) on inflammatory process in acute lung injury (ALI) is unclear. The aims of this study were to 1) examine whether inhaled NO affects the biochemical lung injury parameters and cellular inflammatory responses and 2) determine the effect of inhaled NO on the activation of nuclear factor-kappa B (NF-kappa B) in lipopolysaccharide (LPS)-induced ALI. Compared with saline controls, rabbits treated intravenously with LPS showed increases in total protein and lactate dehydrogenase in the bronchoalveolar lavage (BAL) fluid, indicating ALI. LPS-treated animals with NO inhalation (LPS-NO) showed significant decreases in these parameters. Neutrophil numbers in the BAL fluid, the activity of reactive oxygen species in BAL cells, and the levels of interleukin (IL)-1 beta and IL-8 in alveolar macrophages were increased in LPS-treated animals. In contrast, neutrophil numbers and these cellular activities were substantially decreased in LPS-NO animals, compared with LPS-treated animals. NF-kappa B activation in alveolar macrophages from LPS-treated animals was also markedly increased, whereas this activity was effectively blocked in LPS-NO animals. These results suggest that inhaled NO attenuates LPS-induced ALI and pulmonary inflammation. This attenuation may be associated with the inhibition of NF-kappa B activation.
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PMID:Inhaled nitric oxide attenuates acute lung injury via inhibition of nuclear factor-kappa B and inflammation. 1179 94

Previously, we described the inhibition of proinflammatory mediators such as nitric oxide, tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E2 by taurine chloramine (Tau-Cl) in activated rodent macrophages. We also demonstrated that Tau-Cl suppressed superoxide anion, IL-6, and IL-8 production in activated human polymorphonuclear leukocytes separated from peripheral blood. In these studies, we report the effect of Tau-Cl on lymphocyte proliferation and the production of cytokines by activated human peripheral blood mononuclear leukocytes. Adherent and nonadherent leukocytes were activated using lipopolysaccharide (LPS) and phytohemagglutinin (PHA), respectively, in the presence or absence of Tau-Cl. Tau-Cl significantly suppressed lymphocyte proliferation as measured by tritiated (3H) thymidine. Production of IL-6, IL-8, and IL-2 in PHA-activated nonadherent leukocytes was inhibited by Tau-Cl. The production of IL-1beta, IL-6, and IL-8 was also decreased in LPS-activated adherent monocytes by Tau-Cl. These data demonstrate that the ability of Tau-Cl to modulate the immune response is not species specific and extends to human leukocytes.
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PMID:Taurine chloramine inhibits lymphocyte proliferation and decreases cytokine production in activated human leukocytes. 1184 60

Suberoylanilide hydroxamic acid (SAHA) is a hydroxamic acid-containing hybrid polar molecule; SAHA specifically binds to and inhibits the activity of histone deacetylase. Although SAHA, like other inhibitors of histone deacetylase, exhibits antitumor effects by increasing expression of genes regulating tumor survival, we found that SAHA reduces the production of proinflammatory cytokines in vivo and in vitro. A single oral administration of SAHA to mice dose-dependently reduced circulating TNF-alpha, IL-1-beta, IL-6, and IFN-gamma induced by lipopolysaccharide (LPS). Administration of SAHA also reduced hepatic cellular injury in mice following i.v. injection of Con A. SAHA inhibited nitric oxide release in mouse macrophages stimulated by the combination of TNF-alpha plus IFN-gamma. Human peripheral blood mononuclear cells stimulated with LPS in the presence of SAHA released less TNF-alpha, IL-1-beta, IL-12, and IFN-gamma (50% reduction at 100-200 nM). The production of IFN-gamma stimulated by IL-18 plus IL-12 was also inhibited by SAHA (85% at 200 nM). However, SAHA did not affect LPS-induced synthesis of the IL-1-beta precursor, the IL-1 receptor antagonist, or the chemokine IL-8. In addition, IFN-gamma induced by anti-CD3 was not suppressed by SAHA. Steady-state mRNA levels for LPS-induced TNF-alpha and IFN-gamma in peripheral blood mononuclear cells were markedly decreased, whereas IL-8 and IL-1-beta mRNA levels were unaffected. Because SAHA exhibits antiinflammatory properties in vivo and in vitro, inhibitors of histone deacetylase may stimulate the expression of genes that control the synthesis of cytokines and nitric oxide or hyperacetylate other targets.
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PMID:The antitumor histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits antiinflammatory properties via suppression of cytokines. 1186 42

An excess of the proinflammatory substance IL-18 is present in joints of patients with rheumatoid arthritis (RA), and expression of IL-18 receptor (IL-18R) regulates IL-18 bioactivity in various cell types. We examined the expression of IL-18R alpha-chain and beta-chain and the biologic effects of IL-18 in fibroblast-like synoviocytes (FLS) after long-term culture. The presence of both IL-18R chains was a prerequisite for IL-18 signal transduction in FLS. However, all FLS cultures studied were either resistant or barely responsive to IL-18 stimulation as regards cell proliferation, expression of adhesion molecules ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and the release of interstitial collagenase and stromelysin, IL-6 and IL-8, prostaglandin E2, or nitric oxide. We conclude that the presence of macrophages or IL-18R+ T cells that can respond directly to IL-18 is essential for the proinflammatory effects of IL-18 in synovitis in RA.
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PMID:Expression of interleukin-18 receptor in fibroblast-like synoviocytes. 1187 50

Gastric Helicobacter pylori infection may lead to multifocal atrophic corpus gastritis associated with loss of epithelial cells as well as glandular structures. The current work investigated H. pylori effects on cell death of isolated, nontransformed rat parietal cells (PC). Highly enriched rat PC (>97%) were isolated from gastric mucosa and cultured in serum-free medium over 24 h. The cells were cocultured over 8 h with cytotoxin-associated immunodominant protein (cagA)(+)/vacuolating toxin (vacA)(+) or with cagA(-)/vacA(-) H. pylori laboratory strains and also with H. pylori mutants deleted in several genes of the cag pathogenicity island. Staphylococcus aureus or Campylobacter jejuni were used as controls. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and electron microscopy. Interleukin (IL)-8 and cytokine-induced neutrophil chemoattractant (CINC)-1 secretion was measured by ELISA. Activation of nuclear factor-kappaB (NF-kappaB) was studied in nuclear extracts of PC by electrophoretic mobility shift assay. Apoptosis of PC was induced in a concentration- and time-dependent manner by cagA(+)/vacA(+) H. pylori strains but not by cagA(-)/vacA(-) negative strains or by the cagE knockout mutant. S. aureus and C. jejuni had no effect. PC showed no IL-8 or CINC-1 secretion on exposure to cagA(+)/vacA(+) H. pylori. cagA(+)/vacA(+) strains induced activation of NF-kappaB complexes in nuclear extracts of PC, which were composed of p65 and p50 subunits. No significant stimulation of NF-kappaB activation was detected by incubation of PC with the cagE knockout mutant. Preincubation of PC with antisense but not missense oligodeoxynucleotides against the p65 subunit significantly reduced DNA binding to the kappaB recognition sequence. The p65 oligonucleotides as well as the proteasome inhibitor N-CBZ-isoleucin-glutamin-(o-t-butyl-)-alanin-leucin and the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine completely prevented PC apoptosis induced by cagA(+)/vacA(+) strains. In summary, cagE presence appears to be essential for H. pylori-induced apoptosis of gastric parietal cells, and this effect is dependent on the activation of NF-kappaB and production of nitric oxide.
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PMID:Helicobacter pylori induces apoptosis of rat gastric parietal cells. 1212 77

Dengue virus (DV) primarily infects blood monocytes (MO) and tissue macrophages (M phi). We have shown in the present study that DV can productively infect primary human MO/M phi regardless of the stage of cell differentiation. After DV infection, the in vitro-differentiated MO/M phi secreted multiple innate cytokines and chemokines, including tumor necrosis factor alpha, alpha interferon (IFN-alpha), interleukin-1 beta (IL-1 beta), IL-8, IL-12, MIP-1 alpha, and RANTES but not IL-6, IL-15, or nitric oxide. Secretion of these mediators was highlighted by distinct magnitude, onset, kinetics, duration, and induction potential. A chemokine-to-cytokine hierarchy was noted in the magnitude and induction potential of secretion, and a chemokine-to-cytokine-to-chemokine/Th1 cytokine cascade could be seen in the production kinetics. Furthermore, we found that terminally differentiated MO/M phi cultured for more than 45 days could support productive DV infection and produce innate cytokines and chemokines, indicating that these mature cells were functionally competent in the context of a viral infection. In addition, DV replication in primary differentiated human MO/M phi was enhanced and prolonged in the presence of lipopolysaccharide (LPS), and LPS-mediated synergistic production of IFN-alpha could be seen in DV-infected MO/M phi. The secretion of innate cytokines and chemokines by differentiated MO/M phi suggests that regional accumulation of these mediators may occur in various tissues to which DV has disseminated and may thus result in local inflammation. The LPS-mediated enhancement of virus replication and synergistic IFN-alpha production suggests that concurrent bacterial infection may modulate cytokine-mediated disease progression during DV infection.
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PMID:Activation of terminally differentiated human monocytes/macrophages by dengue virus: productive infection, hierarchical production of innate cytokines and chemokines, and the synergistic effect of lipopolysaccharide. 1220 65

Nitric oxide and superoxide form the unstable compound, peroxynitrite, which can nitrate proteins and compromise function of proinflammatory cytokines at sites of inflammation. Reduced function of proinflammatory proteins such as IL-8, macrophage inflammatory protein-1alpha, and eotaxin suggest an anti-inflammatory effect of nitration. The effects of nitration on anti-inflammatory cytokines such as IL-10 are unknown. We hypothesized that peroxynitrite would modify the function of anti-inflammatory cytokines like IL-10. To test this hypothesis, the capacity of recombinant human IL-10 to inhibit production of human IL-1beta (IL-1) from LPS-stimulated human PBMC was evaluated. Human IL-10 was nitrated by incubation with peroxynitrite or by incubation with 3-morpholinosydnonimine, a peroxynitrite generator, for 2 h and then incubated with LPS-stimulated PBMC for 6 h, and IL-1 was measured in the culture supernatant fluids. Human IL-1 production was significantly lower in the peroxynitrite- or 3-morpholinosydnonimine-nitrated IL-10 group than in the IL-10 controls (p < 0.05, all comparisons). This finding demonstrates that although peroxynitrite inhibits proinflammatory cytokines, it may augment anti-inflammatory cytokines and further point to an important role for peroxynitrite in the regulation of inflammation.
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PMID:Enhanced activity of human IL-10 after nitration in reducing human IL-1 production by stimulated peripheral blood mononuclear cells. 1237 Mar 94

This study was designed to investigate the effects of rhein, the active metabolite of diacerhein, on the metabolic functions of human chondrocytes cultured in alginate beads. Enzymatically isolated osteoarthritic (OA) chondrocytes were cultured in alginate beads in a well-defined culture medium for 12 days. Rhein was tested in a range of concentrations comprised between 10(-7) and 4 x 10(-5)M, in the presence or absence of 10(-10)M IL-1beta. Interleukin (IL)-6 and -8, macrophage inflammatory protein (MIP-1beta), stromelysin-1 (MMP-3), aggrecan (AGG), tissue inhibitor of metalloproteinases-1 (TIMP-1), prostaglandin E(2) (PGE(2)) and nitric oxide (NO) productions were assayed. Cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) mRNA steady-state levels were also quantified. In the basal condition, 10(-5)M rhein increased by 46.5% the production of AGG, decreased by 17-30% the production of IL-6, MMP-3, NO and MIP-1beta but enhanced by 50% the production of PGE(2). IL-1beta increased IL-6, IL-8, MIP-1beta, NO, PGE(2) and MMP-3 productions, but inhibited AGG and TIMP-1 synthesis. Rhein partially reversed the effect of IL-1beta on TIMP-1 and NO production, had no effect on AGG, IL-6 and MIP-1beta production, but up-regulated the IL-1beta stimulated PGE(2) production. The COX-2 and iNOS mRNA levels and IL-8 production were not modified by rhein.Overall, these results contribute to explain the clinical efficiency of rhein and give new information on its mechanisms of action.
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PMID:Effects of rhein on human articular chondrocytes in alginate beads. 1252 30


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