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)

NF-IL6 was originally identified as a DNA-binding protein responsible for IL-1-stimulated IL-6 induction. Direct cloning of NF-IL6 revealed its homology with C/EBP. C/EBP is expressed in liver and adipose tissues and is supposed to regulate several hepatocyte- and adipocyte-specific genes. In contrast, NF-IL6 is suppressed in normal tissues, but is rapidly and drastically induced by LPS or inflammatory cytokines such as IL-1, TNF, and IL-6. NF-IL6 can also bind to the regulatory region of various genes including IL-8, G-CSF, IL-1 and immunoglobulin genes. Furthermore, NF-IL6 is shown to be identical to IL-6DBP, a DNA-binding protein responsible for IL-6-mediated induction in acute-phase proteins, demonstrating that NF-IL6 is responsible for the genes regulated by IL-6. These results indicate that NF-IL6 may be a pleiotropic mediator of many inducible genes involved in acute, immune, and inflammatory responses, like NFkB. In this regard, it is noteworthy that both an NF-IL6 binding site and an NFkB binding site are present in the inducible genes such as IL-6, IL-8, and several acute-phase genes. On the other hand, accumulating evidence has revealed that overproduction of IL-6 may be responsible for the pathogenesis and/or several symptoms of a variety of diseases, including autoimmune diseases, malignancies, and viral diseases. At present, the molecular mechanisms of abnormal expression of the IL-6 gene are not known. Recently it has become evident that interplays between viral proteins and cellular proteins play an important role in viral oncogenesis and infection. The fact that NF-IL6 binds to the enhancer core sequences of various viruses strongly suggests a possible relationship of virus infection and IL-6 expression. In fact some evidence (Mahe et al. 1991, Spergel et al. 1992) indicates that NF-IL6 may interact with viral gene enhancers or viral products, although there are no definite data about the involvement of NF-IL6 in viral pathogenesis. Future studies will be required to clarify whether or not the interplay between NF-IL6 and viral infection is responsible for deregulation of the IL-6 gene.
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PMID:IL-6 and NF-IL6 in acute-phase response and viral infection. 138 Apr 88

To determine the role of the airway epithelial cell in mediating virus-induced inflammation, we infected primary cultures of human airway epithelial cells with human influenza type A/Port Chalmers/72 (H3N2). After two days, the medium was collected for measurement of the chemotactic cytokine interleukin-8 by enzyme-linked immunosorbent assay. The RNA was extracted from the cells for analysis of interleukin-8 mRNA by Northern blot analysis. Interleukin-8 production was more than doubled by viral infection, while interleukin-8 mRNA was increased four-fold. Thus induction of interleukin-8 gene expression in virus-infected airway epithelium may be an important early step leading to virus-induced airway inflammation.
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PMID:Influenza virus A infection induces interleukin-8 gene expression in human airway epithelial cells. 151 5

Human alveolar macrophages (AM) are susceptible to infection with respiratory syncytial virus (RSV), but the infection is abortive after the initial cycles of virus replication. We have investigated if RSV infection of AM results in the production of cytokines TNF, IL-6, and IL-8, all of which may modulate inflammatory and immune responses to the virus, as well as may directly protect respiratory epithelial cells against spread of infection. Within 1 h after interaction with RSV, increased mRNA levels were found for all three cytokines. Peak expression of the mRNAs occurred at 3 to 6 h. The virus most effectively induced TNF mRNA expression greater than IL-6 mRNA greater than IL-8 mRNA, as compared to cytokine mRNA expression induced by bacterial endotoxin. Inactivated virus was almost as effective as live virus in inducing and maintaining increased IL-6 and IL-8 mRNA over 16 h, whereas live infectious RSV was necessary for maintaining TNF mRNA expression over the same time. Protein concentrations of the different cytokines in the supernatants of infected AM reflected the increased levels of mRNA in the cells. Despite the high levels of cytokines with possible antiviral activity (TNF and IL-6) in the AM supernatants, neither supernatants nor rTNF when added to bronchial epithelial cells protected them from infection with RSV. However, TNF, IL-1, and RSV, but not IL-6, induced IL-8 and IL-6 mRNA expression by the bronchial epithelial cells suggesting that cytokines produced by RSV-infected AM may be more important in modulating the inflammatory response in infection than directly interfering with virus infection/replication of airway epithelium.
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PMID:Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophages. 175 1

The imidazoquinolineamine derivative 1-(2-methyl propyl)-1H-imidazole [4,5-c]quinoline-4-amine (imiquimod) has been shown to induce alpha interferon (IFN-alpha) synthesis both in vivo and in peripheral blood mononuclear cells in vitro. In this study, we show that, in these cells, imiquimod induces expression of several IFNA genes (IFNA1, IFNA2, IFNA5, IFNA6, and IFNA8) as well as the IFNB gene. Imiquimod also induced the expression of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha genes. Expression of all these genes was transient, independent of cellular protein synthesis, and inhibited in the presence of tyrosine kinase and protein kinase C inhibitors. Infection with Sendai virus led to expression of a similar set of cytokine genes and several of the IFNA genes. Imiquimod stimulates binding of several induction-specific nuclear complexes: (i) the NF-kappa B-specific complexes binding to the kappa B enhancer present in the promoters of all cytokine genes, but not in IFNA genes, and (ii) the complex(es) binding to the A4F1 site, 5'-GTAAAGAAAGT-3', conserved in the inducible element of IFNA genes. These results indicate that imiquimod, similar to viral infection, stimulates expression of a large number of cytokine genes, including IFN-alpha/beta, and that the signal transduction pathway induced by both of these stimuli requires tyrosine kinase and protein kinase activity.
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PMID:Stimulation of interferon and cytokine gene expression by imiquimod and stimulation by Sendai virus utilize similar signal transduction pathways. 753 79

Rhinovirus infections cause over one third of all colds and are a contributing factor to exacerbations of asthma. To gain insights into the early biochemical events that occur in infected epithelial cells, we develop, for the first time, a model in which a pure respiratory epithelial cell population can be routinely infected by rhinovirus. Viral infection was confirmed by demonstrating that viral titers of supernatants and lysates from infected cell increased with time and by PCR. Infection by rhinovirus 14 was inhibited by homotypic antiserum and by antibodies to intercellular adhesion molecule-1 (ICAM-1), the receptor for this virus. Susceptibility of epithelial cells to infection by rhinovirus 14 (but not rhinovirus 2, an ICAM-1 independent strain) can be increased by preexposure of cells to TNF alpha, whereas IFN gamma reduces susceptibility to infection by both rhinovirus strains. Rhinovirus infection per se does not markedly alter ICAM-1 expression on epithelial cells. Finally, we demonstrate that rhinovirus infection induced increased production of IL-8, IL-6, and GM-CSF from epithelial cells. Production of IL-8 correlated with viral replication during the first 24 h after infection. This model should provide useful insights into the pathogenesis of rhinovirus infections.
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PMID:Infection of a human respiratory epithelial cell line with rhinovirus. Induction of cytokine release and modulation of susceptibility to infection by cytokine exposure. 761 27

Interleukin-8 (IL-8) is a proinflammatory cytokine released at sites of tissue damage by various cell types. One important function of IL-8 is to recruit neutrophils into sites of inflammation and to activate their biological activity. Stromal keratitis induced by herpes simplex virus type 1 (HSV-1) is characterized by an initial infiltration of neutrophils. This study was carried out to determine whether cells resident in the cornea synthesize IL-8 after virus infection. Pure cultures of epithelial cells and keratocytes established from human corneas were infected with HSV-1, and the medium overlying the cells was subsequently assayed for IL-8 by an enzyme-linked immunosorbent assay. Cytokine mRNA levels in cell lysates were monitored by Northern (RNA) blot analysis. It was found that virus infection of keratocyte cultures led to the synthesis of IL-8-specific mRNA with more than 30 ng of IL-8 made per 10(6) cells. Neither UV-inactivated virus nor virus-free filtrates collected from HSV-1-infected keratocytes could induce IL-8 protein or mRNA, suggesting that viral gene expression was needed for induction of IL-8 gene expression. Unlike keratocytes, HSV-1-infected epithelial cells failed to synthesize IL-8 protein or mRNA. However, these cells readily produced both molecules following tumor necrosis factor alpha stimulation. HSV-1 had similar titers in both cell types. Thus, the failure to induce IL-8 synthesis was not due to an inability of the virus to replicate in epithelial cells. The capacity of HSV-1-infected corneal keratocytes to synthesize IL-8 suggests that these cells can contribute to the induction of the acute inflammatory response seen in herpes stromal keratitis.
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PMID:Induction of interleukin-8 gene expression is associated with herpes simplex virus infection of human corneal keratocytes but not human corneal epithelial cells. 768 2

Phagocytosis of Mycobacterium tuberculosis by human monocytes or macrophages is classically followed by granuloma formation in vivo. Granuloma are comprised of cells of the monocyte lineage together, in many instances, with antigen-specific T lymphocytes. Development of granuloma depends upon recruitment of both cell types, but recruitment of monocytes is pivotal as these cells secrete anti-mycobacterial cytokines and IL-8, a T cell chemoattractant. We have therefore investigated gene regulation of Monocyte Chemotactic Protein 1 (MCP-1), an important monocyte chemotactic cytokine, following phagocytosis of particulate material (latex beads and zymosan) and live M. tuberculosis by two human monocytic cell lines. In THP-1 cells and phenotypically more differentiated Mono Mac 6 cells, MCP-1 mRNA accumulation was first detectable by Northern analysis of 4 hours and increased over 24 hours. Magnitude and kinetics of MCP-1 gene expression was independent of the biochemical nature of the phagocytic stimulus, M. tuberculosis strain virulence or pre-treatment with anti-TNF. In contrast to the uniform effect of different phagocytic stimuli on MCP-1 gene expression, we have shown that M. tuberculosis but not latex or zymosan, increased IL-8 gene expression, a chemotactic agent for T cells. In additional experiments with THP-1 cells infected with human immunodeficiency virus (HIV), viral infection did not alter MCP-1 gene expression following phagocytosis. MCP-1 gene expression appears to be a conserved antigen-independent response of human monocytic cells which is activated following particulate phagocytosis. MCP-1 gene expression may thus be involved in recruitment of monocytes during granuloma formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phagocytosis of Mycobacterium tuberculosis or particulate stimuli by human monocytic cells induces equivalent monocyte chemotactic protein-1 gene expression. 768 73

Interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are important mediators of inflammation and immune response in human disease. To demonstrate their importance in pathophysiological processes in liver disease, we measured the circulating levels of IL-8 and GM-CSF in patients with hepatocellular carcinoma (HCC) and chronic active hepatitis (CAH). IL-8 and GM-CSF levels in serum samples were determined with highly specific and sensitive enzyme-linked immunosorbent assays. IL-8 levels were more elevated in serum samples of patients with HCC and CAH associated with hepatitis C virus infection than HCC and CAH associated with hepatitis B virus infection. However, in all patients with autoimmune CAH and in some patients with HCC and CAH, GM-CSF levels were elevated over the baseline levels measured in all of the normals, but this difference was not statistically significant for any group. We conclude that IL-8 and GM-CSF are increased in some patients with liver diseases, and as such they may play a significant role in host defense and disease.
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PMID:Interleukin-8 and granulocyte-macrophage colony-stimulating factor secretion in hepatocellular carcinoma and viral chronic active hepatitis. 785 12

Epithelial cells lining respiratory airways can participate in inflammation in a number of ways. They can act as target cells, responding to exposure to a variety of inflammatory mediators and cytokines by altering one or several of their functions, such as mucin secretion, ion transport, or ciliary beating. Aberrations in any of these functions can affect local inflammatory responses and compromise pulmonary defense. For example, oxidant stress can increase secretion of mucin and depress ciliary beating efficiency, thereby affecting the ability of the mucociliary system to clear potentially pathogenic microbial agents. Recent studies have indicated that airway epithelial cells also can act as "effector" cells, synthesizing and releasing cytokines, lipid mediators, and reactive oxygen species in response to a number of pathologically relevant stimuli, thereby contributing to inflammation. Many of these epithelial-derived substances can act locally, affecting both neighboring cells and tissues, or, via autocrine or paracrine mechanisms, affect structure and function of the epithelial cells themselves. Studies in our laboratories utilized cell cultures of both human and guinea pig tracheobronchial and nasal epithelial cells, and isolated human nasal epithelial cells, to investigate activity of respiratory epithelial cells in vitro as sources of cytokines and inflammatory mediators. Primary cultures of guinea pig and human tracheobronchial and nasal epithelial cells synthesize and secrete low levels of IL-6 and IL-8 constitutively. Production and release of these cytokines increases substantially after exposure to specific inflammatory stimuli, such as TNF or IL-1, and after viral infection.
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PMID:Interactions between respiratory epithelial cells and cytokines: relationships to lung inflammation. 803 Sep 84

Single binding sites for transcription factors NF-IL6 and NF-kappa B are present in the promoter of the interleukin (IL) 6 gene. Previous studies of internally deleted promoter mutants demonstrated that these two sites are important for the transcriptional regulation of this gene. In this report, we describe the synergistic activation of the IL-6 promoter by transcription factors NF-IL6 and NF-kappa B. Cotransfection of NF-IL6 with the NF-kappa B p65 subunit resulted in strong synergistic activation of an IL-6 promoter-reporter construct. Both the NF-IL6 and NF-kappa B binding sites in the IL-6 promoter were required for synergistic activation. Similar synergistic activation was observed in the IL-8 promoter, which also contains both NF-IL6 and NF-kappa B binding sites. Furthermore, we demonstrated that NF-IL6 and the NF-kappa B p65 subunit directly associated via the basic leucine-zipper domain of NF-IL6 and the Rel homology domain of p65. Since the promoters of many other genes involved in the inflammatory and acute-phase responses also contain binding sites for NF-IL6 and NF-kappa B, the cooperation between these two factors may have an important role in these responses. We also discuss the possible interplay between various viral gene products and these two factors in the process of viral infection and constitutive cytokine production.
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PMID:Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. 823 76


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