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)

Cells of the synovial microenvironment may recruit neutrophils (PMN) and lymphocytes into synovial fluid, as well as lymphocytes into the synovial tissues, of arthritic patients. We have investigated the production of the chemotactic cytokine IL-8 by using sera, synovial fluid, synovial tissue, and macrophages and fibroblasts isolated from synovial tissues from 75 arthritic patients. IL-8 levels were higher in synovial fluid from rheumatoid (RA) patients (mean +/- SE, 14.37 +/- 5.8 ng/ml), compared with synovial fluid from osteoarthritis patients (0.135 +/- 17 ng/ml) (p less than 0.05) or from patients with other arthritides (5.52 +/- 5.11 ng/ml). IL-8 from RA sera was 8.44 +/- 2.33 ng/ml, compared with nondetectable levels found in normal sera. IL-8 levels from RA sera and synovial fluid were strongly positively correlated (r = 0.96, p less than 0.05). Moreover, RA synovial fluid chemotactic activity for PMN in these fluids was inhibited 40 +/- 5% upon incubation with neutralizing polyclonal antibody to IL-8. Synovial tissue fibroblasts released only small amounts of constitutive IL-8 but could be induced to produce IL-8 by stimulation with either IL-1 beta, TNF-alpha, or LPS. In contrast, unlike normal PBMC or alveolar macrophages, macrophages isolated from RA synovial tissue constitutively expressed both IL-8 mRNA and antigenic IL-8. RA synovial macrophage IL-8 expression was not augmented by incubation with either LPS, TNF-alpha, or IL-1 beta. Immunohistochemical analysis of synovial tissue showed that a greater percentage of RA macrophages than osteoarthritis macrophages reacted with anti-IL-8. Whereas macrophages were the predominant cell for immunolocalization of IL-8, less than 5% of synovial tissue fibroblasts were positive for immunolocalized IL-8. These results suggest that macrophage-derived IL-8 may play an important role in the recruitment of PMN in synovial inflammation associated with RA.
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PMID:Synovial tissue macrophage as a source of the chemotactic cytokine IL-8. 191 55

Gelatinases (type IV collagenases) produced by normal peripheral blood leukocytes were studied by the use of a substrate conversion assay. When monocytes were stimulated with IL-1 beta discrete amounts of a 85-kDa gelatinase were detected. This type of gelatinase comigrated with a phorbol ester-inducible metalloproteinase from human tumor cells. The levels of induction of the monocytic enzyme after stimulation with IL-1, double-stranded RNA, LPS, and mitogens paralleled those of the secondary cytokine IL-6. When peripheral blood neutrophils were stimulated with IL-8 or PMA significant amounts of a 91-kDa neutrophil gelatinase were released, whereas with IL-1 beta no effect was observed. Both neutrophil and monocyte gelatinases cross-reacted in immunoprecipitation experiments with tumor cell-derived gelatinases. Further evidence for structural similarity between the IL-1-inducible monocytic (85 kDa) and the IL-8-regulated neutrophilic (91 kDa) gelatinases was obtained after purification of the proteins to homogeneity: both gelatinases possessed an identical amino terminal amino acid sequence and appeared as truncated forms of gelatinase from tumor cells. Synovial fluids of arthritic joints contained extremely high concentrations of the 91-kDa gelatinase. The concentrations of this type of gelatinase were correlated with the titers of the marker cytokine IL-6. The controlled production and activity of leukocyte-derived gelatinase may play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. In the arthritis patient this enzyme might contribute to the pathogenesis of joint destruction and might constitute a useful marker of disease status.
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PMID:Cytokine-mediated regulation of human leukocyte gelatinases and role in arthritis. 193 76

The cytokine NAP-1/IL-8 is produced by a variety of different cells in response to inflammatory stimuli and elicits several biological responses from PMN. Experiments presented here demonstrate that PMN exposed to NAP-1/IL-8 expressed increased amounts of CD11b/CD18, as well as CD11c/CD18 and CR1, on their cell surface, while expression of Fc gamma RIII and HLA-A,B,C remained essentially unchanged. Increased CD11b/CD18 and CD11c/CD18 appears to correspond with the release of specific granules by NAP-1/IL-8. NAP-1/IL-8 was also a potent stimulator of several of the binding activities of CD11b/CD18. Ligation of EC3bi by CD11b/CD18 was rapidly enhanced by NAP-1/IL-8, but phagocytosis of the ligated particles was not induced by the agonist. In addition, enhanced binding of EC3bi was observed in the absence of an increase in receptor expression as shown with PMN cytoplasts. NAP-1/IL-8 promoted additional adhesive interactions between CD11b/CD18 and the biosynthetic precursor of LPS, lipid IVa, fibrinogen, and endothelial cells, suggesting that NAP-1/IL-8 may promote leukocyte adhesion in vivo that could lead to recruitment of PMN to sites of tissue inflammation.
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PMID:Neutrophil-activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils. 196 19

Much effort has been directed toward elucidating the host response to sepsis and inflammation, resulting in the definition of a cascade of endogenous mediators that direct metabolic and immunological responses. Here we report that IL-8, a novel cytokine produced by a variety of cells in vitro in response to stimulation with bacterial LPS and the proinflammatory cytokines, appears in the circulation of primates in vivo during septic shock, sublethal endotoxemia, and after the administration of IL-1 alpha. The magnitude of the IL-8 response correlates with the severity of the insult, and levels of IL-8 peak relatively late, after those of TNF-alpha and IL-1 beta, and simultaneously with those of IL-6. IL-8 has been primarily defined as a selective activator and chemoattractant of neutrophils, and we demonstrate that after LPS or IL-1 alpha infusion, circulating neutrophil numbers rapidly recover from an initial neutropenia while IL-8 concentrations are maximal, supporting the hypothesis that IL-8 influences circulating leukocyte populations in vivo. We conclude that IL-8 is another participant in the cytokine cascade elicited by sepsis and inflammation and, as such, may play a significant role in host defense and disease.
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PMID:IL-8 in septic shock, endotoxemia, and after IL-1 administration. 202 76

NF-IL6 is a nuclear factor that specifically binds to an IL1-responsive element in the IL-6 gene. In this study the gene encoding NF-IL6 has been cloned by direct screening of a lambda gt11 library using NF-IL6 binding sequence as a ligand. The full-length cDNA encoded a 345 amino acid protein with a potential leucine zipper structure and revealed a high degree of homology to a liver-specific transcriptional factor, C/EBP, at the C-terminal portion. The bacterial fusion protein bound to the CCAAT homology as well as the viral enhancer core sequences as in the case of C/EBP. Recombinant NF-IL6 activated the human IL-6 promoter in a sequence-specific manner. Southern blot analysis demonstrated the high-degree conservation of the NF-IL6 gene through evolution and the existence of several other related genes sharing the DNA-binding domain. NF-IL6 mRNA was normally not expressed, but induced by the stimulation with either LPS, IL-1 or IL-6. Interestingly, NF-IL6 was shown to bind to the regulatory regions for various acute-phase protein genes and several other cytokine genes such as TNF, IL-8 and G-CSF, implying that NF-IL6 has a role in regulation not only for the IL-6 gene but also for several other genes involved in acute-phase reaction, inflammation and hemopoiesis.
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PMID:A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. 211 87

The liver participates in inflammation via the elaboration of acute phase proteins from hepatocytes in response to IL-1, TNF-alpha, and IL-6/INF-beta 2/hepatocyte-stimulating factor. In addition, some inflammatory states of the liver are characterized by leukocyte infiltrates. Here we demonstrate that human hepatocyte lines are capable of expressing mRNA and biologic activity for a neutrophil chemotactic factor (NCF)/IL-8 in response to the inflammatory mediators IL-1 alpha, IL-1 beta, and TNF. Two human hepatoma cell lines (SK-Hep and Hep-G2) displayed a time- and dose-dependent increase in steady state levels of NCF/IL-8 mRNA and secretion of chemotactic activity in response to TNF and IL-1. Neutralizing antibody to NCF/IL-8 inhibited hepatocyte-derived chemotactic activity by 88%. In contrast to IL-1 and TNF, hepatocytes did not respond to LPS or IL-6 within the time and dose parameters used above. Although the expression of NCF/IL-8 mRNA (1.8 kb) was first detectable between 1 and 2 h poststimulation, significant chemotactic bioactivity was not observed until about 4 h. Heat-inactivated (100 degrees C, 30 min) cytokine failed to induced NCF/IL-8 mRNA synthesis, and cotreatment of cells with cytokine and cycloheximide super-induced NCF/IL-8 mRNA while inhibiting production of bioactivity. Thus, NCF/IL-8 expression is a primary induction phenomenon. Our data demonstrate the stimulus specific induction of NCF/IL-8 in hepatocytes and suggest that cytokine cell-to-cell communication circuits may be important in neutrophil-mediated inflammatory processes in the liver.
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PMID:Cytokine-induced gene expression of a neutrophil chemotactic factor/IL-8 in human hepatocytes. 215 28

Human dermal fibroblasts in culture secrete three protein-like neutrophil chemotactic factors, when stimulated either with human rIL-1 alpha or IL-1 beta; not, however, after incubation with LPS. These three fibroblast-derived neutrophil-activating proteins (FINAP) could be purified by subsequently performed reversed phase and size exclusion HPLC. By high resolution SDS-PAGE, all the proteins were shown to migrate with an Mr of 6,700 (alpha-FINAP), 3,600 (beta-FINAP), and 5,300 (gamma-FINAP). All purified cytokine preparations were found to be chemotactic for human neutrophils. In addition, all FINAP induced release of lysosomal enzymes in neutrophils. Deactivation of chemotaxin-elicitable enzyme release showed cross-desensitization of all FINAP with NAP-1/IL-8. Western blot analysis of alpha-FINAP by using mAb against neutrophil-activating protein (NAP)-1/IL-8 reveals immunologic cross-reactivity with NAP-1/IL-8. By amino-terminal amino acid sequence analysis alpha-FINAP could be identified as the 77-residue extended form of NAP-1/IL-8 containing the 79-residue form as a minor contaminant. Whereas beta-FINAP has been found to be a truncation product of alpha-FINAP, gamma-FINAP shows identity with authentic melanoma growth stimulatory activity with respect to retention time upon reversed phase HPLC, high resolution SDS-PAGE, and biologic properties, as well as amino-terminal amino acid sequence. These data show that human dermal fibroblasts may actively participate in inflammatory reactions by secretion of proinflammatory cytokines.
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PMID:IL-1 alpha or tumor necrosis factor-alpha stimulate release of three NAP-1/IL-8-related neutrophil chemotactic proteins in human dermal fibroblasts. 217 8

During the past three years great advances have been made in the chemistry and biology of chemoattractants for human leukocytes. Two chemoattractant cytokines have been isolated, sequenced and cloned, each with distinctive leukocyte attractant specificity. Monocyte chemoattractant protein 1 (MCP-1), the subject of this review by Edward Leonard and Teizo Yoshimura, is secreted by PHA-stimulated mononuclear cells and can be identified by northern blotting in response to LPS or PHA. It attracts monocytes but not neutrophils. In contrast, neutrophil attractant/activation protein (NAP-1) (also known as interleukin 8 (IL-8)) attracts and activates human neutrophils but it is not a chemoattractant for human monocytes. Based on amino acid sequence analysis, each of these attractants has been assigned to one of two distinct families of cytokines that are thought to participate in host defense and inflammatory responses.
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PMID:Human monocyte chemoattractant protein-1 (MCP-1). 218 47

Peripheral blood monocytes are important mediators of inflammation via the generation of various bioactive substances, including the recently isolated and cloned chemotactic peptide IL-8. Through cytokine networking, monocyte-derived cytokines are capable of inducing IL-8 expression from non-immune cells. IL-4, a B and T lymphocyte stimulatory factor, has recently been shown to inhibit monocyte/macrophage function, including the ability to suppress monocyte-generated cytokines. We describe the in vitro inhibition of IL-8 gene expression and synthesis from LPS, TNF, and IL-1 stimulated peripheral blood monocytes by IL-4. IL-4 suppressed IL-8 production from stimulated monocytes in a dose-dependent fashion, with partial suppression observed at IL-4 concentrations as low as 10 pg/ml. The IL-4-induced suppressive effects were observed even when IL-4 was administered 2 h post-LPS-stimulation. The IL-4-induced inhibition of IL-8 mRNA expression was dependent on protein synthesis, as the suppressive effects of IL-4 were significantly negated by the addition of cycloheximide. Our findings suggest that IL-4 may be an important endogenous regulator of inflammatory cell recruitment, and adds further support to the potential role of IL-4 as a down-regulator of monocyte immune function.
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PMID:IL-4 inhibits the expression of IL-8 from stimulated human monocytes. 220 Aug 23

Adherence of monocytes to endothelial cells or extracellular matrices is likely to play a critical role in triggering monocyte activation in extravascular sites of infection, chronic inflammatory disorders, tissue damage and neoplastic growth. We have constructed a cDNA library from monocytes adhered for 30 min on plastic and have screened it by differential hybridization for mRNA rapidly induced by adherence. Two of the cDNA isolated have been identified as IL-1 beta and superoxide dismutase. Sequence data from three other adherence specific clones demonstrates the presence of ATTTA mRNA instability sequences in their 3' untranslated regions signifying inflammation-associated genes. The deduced amino acid sequences indicate the presence of open reading frames with sequence homologies to a family of host defense cytokines, one of them being identified as IL-8. Of the 14 clones initially identified, 4 have been analyzed for induction of mRNA expression. Although 3 of the 4 clones were equally induced by PMA and LPS under nonadherent conditions, all 4 cDNA showed distinct patterns of induction with adherence to extracellular matrix components or endothelial cells. The deduced amino acid sequence homologies indicate that we have isolated cDNA that code for three unique gene products. These cDNA belong to a gene family of early host defense cytokines involved in inflammation and cell growth, but which are differentially regulated by adherence to different surfaces.
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PMID:Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair. 234 26


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