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)

Uptake of [14C]-azithromycin into THP-1 human monocytes was determined at pH 7.4, 6.8 or 5.5 over 4-log antibiotic concentrations for 24 h under a number of conditions. Stimulation of cells was with bacteria, latex beads, lipopolysaccharide (LPS), or zymogen A. Subcellular organelle disposition was determined after isolation by ultracentrifugation or sucrose gradients. Hydrolytic enzyme activities and mediators of intracellular inflammation (IL-1, IL-6, IL-8, and TNFalpha) were assessed. Azithromycin uptake into human THP-1 monocytes was initially linear achieving approximately 2% of the extracellular concentration. At pH 7.4, uptake was both passive- and carrier-mediated, but as the pH became more acidic, the uptake was exclusively passive. The intracellular concentration was not pH-dependent over 24 h. Uptake was dependent upon temperature but not the presence of foetal calf serum. Intracellular disposition in zymogen A-stimulated and unstimulated cells was throughout all compartments of the cell, but was higher in the nucleus and cell sap. Phagosomes of stimulated cells contained higher level of the antibiotic. Efflux from THP-1 monocytes was complete between 3 and 4 h. After 1 h treatment with zymogen A, THP-1 monocytes demonstrated an increase in intracellular acidity, protein kinase C, SOD and NAG activities, and NO, H(2)O(2), TNFalpha and IL-1 release over the 1st h. After 2-4 h the pH became alkaline, activities of NADPH reductase, NAG and cathepsin were reduced, and the release of NO, H(2)O(2), TNFalpha and IL-6 were suppressed. Protein synthesis and killing of the bacteria was evident in bacteria kept in monocyte-free medium and those phagocytized by the THP-1 monocytes moderately at 2 h, but more significantly at 24 h. The early killing of the bacteria appears to be a cidal mechanism whereas later, a standard bacteriostatic mechanism was evident. Nevertheless, suppression of these chemical mediators and hydrolytic enzyme activities would reduce the infection and the spread to adjacent areas.
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PMID:Disposition and intracellular activity of azithromycin in human THP-1 acute monocytes. 1243 70

Epidemiological studies have shown an increase in the number of hospital admissions for respiratory diseases in association with high concentrations of particulate matter smaller than 10 micro m (PM(10)). Diesel exhaust particles (DEP) are important components of PM(10). This study was designed to test the effect of DEP on the release of cytokines from alveolar macrophages (AMs). Human and murine AMs were exposed to DEP for 24 hours, and the concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). DEP (10 micro g/mL) suppressed the spontaneous release of TNF-alpha and IL-6 from murine AMs (P<.05). This suppression was not seen with exposure to carbon particles. Soluble components of DEP had a similar suppressive effect, suggesting that the chemical composition of DEP is responsible for the suppression. Lipopolysaccharide (LPS)- or IFN-gamma-induced TNF-alpha and IL-6 production by murine AMs were suppressed by DEP in a dose-dependent manner (P<.05). DEP also inhibited LPS-stimulated production of TNF-alpha, IL-6, and IL-8 from human AMs (P<.05). Pretreatment of AMs with superoxide dismutase (SOD) (300 IU/mL) prevented the suppressive effect of DEP on AM cytokine production (P<.05). The authors conclude that DEP exposure suppressed the release of cytokines from AMs, and speculate that this suppression could impair normal host defenses.
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PMID:Suppressive effects of diesel exhaust particles on cytokine release from human and murine alveolar macrophages. 1263 27

The aim of this work was to study the induction and secretion of interleukin 8 (IL-8) and some oxidative stress parameters after ethanol (EtOH), acetaldehyde (Ac) or lipopolysaccharide (LPS) treatment on HepG2 cells. Cells were treated with 50 mM EtOH, 175 &mgr;M Ac or 1 &mgr;g/ml of LPS. IL-8 induction and secretion were determined in the presence of the toxics, and the effect of antioxidants N-acetyl-L-cysteine and 1,1,3,3-tetramethyl-2-thiourea was evaluated. Further, the effect of adding polyclonal anti-human tumor necrosis factor alpha (TNF-alpha) and H(2)O(2) was studied, and catalase, superoxide dismutase and glutathione peroxidase activities were determined. Lipid peroxidation increased significantly only in Ac-treated cells. All toxics failed to decrease significantly the intracellular levels of reduced GSH. Catalase activity was diminished in all treatments, while other enzyme activities did not present changes. No change in peroxide production was found with any treatment. IL-8 secretion increased in Ac (41%) and in LPS (38%)-treated cells. Antioxidant and anti-TNF-alpha treatments decreased IL-8 secretion. H(2)O(2) (0.25 mM)-treated cells increased IL-8 secretion. IL-8 reverse transcriptase-polymerase chain reaction results correlated with secretion values. Our results show that Ac and LPS treatment produced an increased IL-8 induction and secretion. Oxidative stress and TNF-alpha are mediators in IL-8 response. This observation suggests that in the in vivo liver, the mechanism of ethanol-induced IL-8 production requires ethanol metabolism, and hepatocytes do not require the interaction among different populations of liver cells to respond.
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PMID:Interleukin 8 response and oxidative stress in HepG2 cells treated with ethanol, acetaldehyde or lipopolysaccharide. 1280 41

To characterize the role of intestinal epithelial cells in mucosal host defense, we have examined endogenous antioxidant reactivity and inflammatory response in Caco-2 cell line. When differentiated Caco-2 cells were incubated with iron/ascorbate for 1-24 h, they exhibited increased malondialdehyde levels and decreased polyunsaturated fatty acid proportion in favor of saturated fatty acids. These modifications were accompanied with alterations in membrane fluidity and permeability. The oxidative stress did not induce changes in the antioxidant enzyme activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione transferase, or in cellular glutathione content. However, iron/ascorbate-mediated lipid peroxidation promoted inhibitor-kappaB degradation and NF-kappaB activation, as well as gave rise to IL-8, cyclooxygenase-2, and ICAM-1. These results support the importance of oxidant/antioxidant balance in the epithelial cell inflammatory response.
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PMID:Inflammatory reaction without endogenous antioxidant response in Caco-2 cells exposed to iron/ascorbate-mediated lipid peroxidation. 1284 21

We have examined the effects of various antioxidants and inhibitors of redox-sensitive signal transduction pathways on induction of interleukin 8 (IL-8) gene by NO in monocytic U937 cells. We have observed that nitrosoglutathione or another NO-generating compound spermine NONOate caused significant accumulation of IL-8 mRNA. Pretreatment of cells with pyrrolidine dithiocarbamate or with antioxidants, which scavenge hydroxyl radical, dimethyl sulfoxide (DMSO), or dimetylthiourea (DMTU) completely abrogated NO-dependent induction of IL-8 gene expression. The transcriptional activation of IL-8 gene was not affected by sodium formate or sodium salicylate, suggesting that suppression of the IL-8 gene induction is specific to the class of hydroxyl radical scavenger used. Furthermore, we have shown that IL-8 induction was not inhibited by catalase and the iron chelator deferoxamine, indicating that the inhibitory actions of DMSO and DMTU are not related to scavenging of reactive oxygen species produced from hydrogen peroxide in the iron-catalyzed reactions. Finally, we have not observed any significant inhibition of NO-dependent IL-8 gene induction by superoxide scavengers such as N-acetyl cysteine, uric acid, and superoxide dismutase. Therefore, it seems likely that in U937 cells, hydroxyl radicals or species with reactivity similar to hydroxyl radicals contribute to NO-mediated IL-8 gene induction.
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PMID:Redox modulation of NO-dependent induction of interleukin 8 gene in monocytic U937 cells. 1290 50

We have studied the oxidative status of 155 semen samples, 95 originating from healthy individuals and 60 from infertile patients, which were subdivided into two groups: (a) normozoospermic with genitourinary tract infection (GTI); and (b) with pathological spermiogram and GTI. Several phases of infection were observed: with bacterial presence only, bacteria and leukocytes, and leukocytes only, following the routine inflammatory pattern. Leukocyte numbers, bacterial strains, pro- and anti-oxidants, and selected pro-inflammatory cytokines (IL-1 beta, IL-6, IL-8 and TNF-alpha) were studied. Additionally, two oxido-sensitive indices were created (SOD/XO and CAT/XO) in order to follow particular phases of semen infection in two subgroups of patients. Different patterns of activities of pro- and anti-oxidant substances, as well as cytokines, were observed in the studied populations. It was reflected mainly by elevated XO activity in a group of patients with a pathological spermiogram while, in a group of patients with GTI and normozoospermia, xanthine oxidase was normal. In the latter group, oxido-sensitive indices were elevated in favour of anti-oxidants; similarly, this occurred with IL-6 levels in comparison to healthy controls. It appears therefore that normozoospermic semen recovers better after infection than pathological semen. Perhaps, IL-6 secretion might be helpful in the observed recovery?
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PMID:Male genital tract infection: an influence of leukocytes and bacteria on semen. 1528 87

Cultured human THP-1 monocytes were exposed to serial concentrations of gemifloxacin over 4 h after pre-stimulation with zymogen A for 1 h or Staphylococcus aureus for 2 h. The following parameters were assessed: pH, phagocytosis, c-AMP, NO, TNFalpha, IL-1, IL-6, IL-8 and H2O2 levels, enzyme activities of protein kinase C, NADPH oxidase, SOD, gluthathion reductase, NAG and cathepsin D as well as lipid peroxidation. The reversiblity of these changes was determined in the presence of known blockers of the phagocytic process. The effects of gemifloxacin on DNA synthesis and killing of S. aureus was assessed in bacteria alone and in those bacteria phagocytosed by THP-1 monocytes over 24 h. Gemifloxacin in stimulated THP-1 monocytes over the first 30 min caused an increase in c-AMP, NO, H2O2 and TNFalpha levels and protein kinase C, NADPH oxidase, glutathione reductase, NAG and cathepsin D activities. The pH became more acidic and phagocytosis was stimulated. These parameters were reversed at 1 h and continued to decline until 4 h. Lipid peroxidation was at the highest levels at 1 h and IL-8 levels at 2 h. DNA synthesis and bacterial growth were suppressed at 2 h in both S. aureus alone and bacteria phagocytosed by THP-1 monocytes. These effects were at a higher magnitude at 24 h. Gemifloxacin initiates a phagocyticidal effect of THP-1 monocytes at an early time of 30 min which plays a role in killing bacteria but a higher magnitude of killing of bacteria occurs later by a standard static mechanism. This early action of gemifloxacin should decrease the spread of infection and the inflammatory response since the tissue destruction process was attenuated at 4 h.
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PMID:In vitro anti-inflammatory effects and immunomodulation by gemifloxacin in stimulated human THP-1 monocytes. 1549 55

Gram-negative bacterial infection predisposes to the development of shock and acute lung injury with multiple organ dysfunction in the critically ill. Although overexpression of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta, IL-6, IL-8, and other mediators is causally implicated in the pathogenesis of shock and lung injury, the underlying mechanisms following cellular exposure to gram-negative endotoxin remain unclear. De novo generation of reactive oxygen species (ROS) by monocytes/macrophages in particular has been proposed as a pivotal regulatory mechanism by which enhanced transactivation of redox-sensitive genes culminates in augmented cytokine expression within the lower respiratory tract. Here we sought to characterize the mechanism of action of a synthetic, nonpeptide, low-molecular-weight, Mn-containing superoxide dismutase mimetic (SODm), M40403, in modulating E. coli lipopolysaccharide serotype 0111:B4 (LPS)-induced cytokine production by cultured rat alveolar macrophages. Intracellular superoxide (O2) ion generation was measured using hydroethidine (HE) dye, and the dose-dependent effects of M40403 on TNF-alpha and IL-6 biosynthesis by ELISAs. Upstream redox-sensitive signaling events involving the pleiotropic transcription factor NF-kappaB were determined in nuclear extracts by electrophoretic mobility shift assays (EMSAs) and p65 subunit Western blot. The levels of the cytosolic inhibitory protein IkappaB-alpha were also assessed by Western analysis. We found that M40403 potently suppressed the production of superoxide, TNF-alpha, and IL-6 in LPS-stimulated alveolar macrophages, suggesting a key role for superoxide in endotoxin-induced cytokine production in the distal air spaces. In addition, M40403 decreased E. coli LPS-induced activation of NF-kappaB, and this effect was associated with modest suppression of cytoplasmic IkappaB-alpha degradation. Together, these results suggest that removal of superoxide by M40403 inhibits endotoxin-induced production of TNF-alpha and IL-6 in alveolar macrophages by a mechanism involving suppression of redox-sensitive NF-kappaB transactivation or signaling.
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PMID:Superoxide potentiates NF-kappaB activation and modulates endotoxin-induced cytokine production in alveolar macrophages. 1566 36

Motorcycle exhaust particles (MEP) are among the major air pollutants, especially in urban area of Taiwan. In our previous study, data showed that MEP induce proinflammatory and proallergic response profiles in BALB/c mice. Effects of MEP on interleukin (IL)-8 production in A549 human airway epithelial cells were further investigated in this study. It was found that MEP enhanced IL-8 protein and mRNA expression in human epithelial cells. Pretreatment with an NF-kappaB inhibitor (1 mM PDTC), extracellular signal-regulated kinase (ERK) inhibitor (50 microM PD98059), JNK inhibitor (25 microM SP600125), p38 inhibitor (2 microM SB203580), and three antioxidants (500 U/ml superoxide dismutase [SOD], 50 microM vitamin E, 10 mMN-acetylcysteine [NAC]) attenuated the MEP-induced increase in IL-8 production. Through further, direct detection of nuclear factor (NF)-kappaB activation in epithelial cells using immunoblotting of nuclear p65 and NF-kappaB reporter assay, data showed that MEP induced nuclear translocation of p65 and enhancement of NF-kappaB luciferase gene expression. MEP also induced activation of ERK, JNK, and p38 signaling pathways and produced an increase of oxidative stress in A549 cells. By using mitogen-activated protein kinase (MAPK) inhibitors and antioxidant, it was demonstrated that ERK inhibitor, JNK inhibitor, and antioxidants but not p38 inhibitor attenuated the MEP-induced increase in NF-kappaB reporter activity. In conclusion, evidence shows that filter-trapped particles emitted from unleaded gasoline-fueled, two-stroke motorcycle engines induce an increase in IL-8 production by activation of NF-kappaB in human airway epithelial cells.
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PMID:Motorcycle exhaust particles induce IL-8 production through NF-kappaB activation in human airway epithelial cells. 1607 65

Lung injury after asbestos exposure is associated with an oxidative stress that is catalyzed by iron in the fiber matrix, complexed to the surface, or both. We tested the hypothesis that the cellular response to asbestos includes the transport and sequestration of this iron through (1) generation of superoxide for ferrireduction, (2) up-regulation of divalent metal transporter-1 (DMT1) for intracellular transport of Fe2+, and (3) increased production of cellular ferritin where the metal is stored in a catalytically less reactive state. BEAS-2B cells with normal and elevated Cu,Zn superoxide dismutase (SOD) expression were employed for in vitro investigations. After exposure of these cells to asbestos, we demonstrated by fluorescence methodology a significantly increased generation of SOD with ferrireductive capacity. Fiber exposure also increased DMT1 protein and mRNA expression in the BEAS-2B cells. Incubation with asbestos elevated cellular iron and ferritin concentrations, and these responses were diminished in cells with an enhanced expression of SOD. Finally, fiber exposure increased supernatant concentrations of interleukin 8, but this inflammatory mediator was actually increased in cells with elevated SOD expression. We conclude that the response of respiratory epithelial cells to asbestos includes oxidant-mediated mechanisms to sequester catalytically active iron associated with the fiber.
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PMID:Oxidant generation promotes iron sequestration in BEAS-2B cells exposed to asbestos. 1627 61


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