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)

In order to elucidate the role of inflammatory cytokines in the central nervous system (CNS), we examined whether IL and TNF-alpha induce cells in the CNS to produce two newly identified leucocyte chemo-attractants, IL-8 and monocyte chemotactic and activating factor (MCAF). Several human astrocytoma and glioblastoma cell lines expressed high levels of IL-8 and MCAF mRNA in vitro upon stimulation with IL-1 and TNF-alpha. In particular, an astrocytoma cell line U373MG subclone responded markedly to IL-1 with high expression levels of IL-8 and MCAF mRNA as well as IL-6 mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-1 and appeared as early as 30 min to 1 hr after IL-1 stimulation, confirming that these are early inducible genes. The production of IL-8 and MCAF in the U373MG cell culture supernatants was confirmed by a competitive radioimmunoassay (RIA) as well as chemotactic activities on human neutrophils and monocytes. IL-1-induced IL-8 and MCAF mRNA expression appeared to occur at least at the transcriptional level as revealed by a nuclear run-off assay. Moreover, IL-1 treatment increased the half-life of IL-8 and MCAF mRNA markedly, suggesting that increased mRNA stability was also responsible for the enhanced gene transcription. These data suggest that IL-1 and TNF-alpha induce astrocytes to produce IL-8 and MCAF transcriptionally and post-transcriptionally, both of which may be responsible for leucocytosis seen in inflammation of the CNS.
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PMID:IL-1 and TNF-alpha induction of IL-8 and monocyte chemotactic and activating factor (MCAF) mRNA expression in a human astrocytoma cell line. 193 74

Based on observations of fluctuations in progenitors for inflammatory cells during allergic responses, we have proposed that a primary determinant of allergic inflammation involves microenvironmental influences on hemopoietic cell differentiation and phenotype; in addition, as a corollary of this, inflammatory cell burden is proposed as an important indicator of the severity and pattern of the inflammatory process in allergy. The studies outlined here focus on the effects of epithelial-cell- and fibroblast-derived cytokines on granulocytic and monocytic cell differentiation and activation in models involving allergic reactions in the upper and lower airways. Pure cultures of nasal or bronchial epithelial cells or fibroblasts are observed to give rise to cytokines important in inducing the differentiation of basophils, eosinophils, neutrophils and monocyte/macrophages. Gene expression, production and secretion of granulocyte/macrophage-colony-stimulating factor, interleukin-6 (IL-6) and IL-8 can be demonstrated in vitro and in vivo. Up-regulation of gene expression and production of these cytokines, which are important in inducing basophil, eosinophil and neutrophil/macrophage differentiation in several assays, is seen with IL-1 and the neuropeptide substance P; conversely, inhibition of cytokine production by structural cells is observed after pretreatment with corticosteroids in vitro, paralleling in vivo effects. Other modulatory effects also examined include: antiallergic compounds, which may affect posttranscriptional events in cytokine production, and heavy metal ions, which can also induce changes in gene expression. Structural-cell-derived extracellular matrices appear also to be important both in mast cell differentiation and in macrophage cytokine gene expression, both of which potentially feedback upon chronic allergic inflammatory processes, leading to their perpetuation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structural cell-derived cytokines in allergic inflammation. 193 66

The role of neutrophil chemoattractant receptors in neutrophil stimulation in vitro is well established, however, the precise mechanisms underlying local neutrophil accumulation at inflammatory sites in vivo have not been defined. A fundamental question that remains open is whether chemoattractants act on the endothelial cell or the neutrophil to initiate the process of neutrophil migration in vivo. To address this question we have investigated whether neutrophil accumulation in vivo can occur if chemoattractant receptor occupancy is uncoupled from neutrophil stimulation. For this purpose we have used pertussis toxin (PT) as the pharmacologic tool. We have investigated the effect of in vitro pretreatment of rabbit neutrophils with PT on their responses in vitro and on their accumulation in vivo. Pretreatment of rabbit neutrophils with PT inhibited FMLP- and C5a-, but not PMA- induced increases in CD18 expression, neutrophil adherence, and degranulation in vitro. This pretreatment procedure with PT inhibited the accumulation of radiolabeled neutrophils in vivo in response to intradermally injected FMLP, C5a, C5a des Arg, leukotriene B4, IL-8, and zymosan in rabbit skin. Further, in contrast to the in vitro results, PT inhibited the PMA-induced 111In-neutrophil accumulation in vivo. Interestingly, pretreatment of neutrophils with PT also inhibited accumulation in response to intradermally injected IL-1, despite the reports that IL-1 lacks neutrophil chemoattractant activity in vitro. Although the experimental techniques used cannot distinguish the different stages of neutrophil migration involved, these results suggest that the accumulation of neutrophils induced by local extravascular chemoattractants in vivo depends on a pertussis toxin-sensitive receptor operated event on the neutrophil itself. Further, PMA and IL-1 may release secondary chemoattractants in vivo.
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PMID:Evidence that a receptor-operated event on the neutrophil mediates neutrophil accumulation in vivo. Pretreatment of 111In-neutrophils with pertussis toxin in vitro inhibits their accumulation in vivo. 197

We report here that human synovial cells stimulated by interleukin-1 alpha and interleukin-1 beta express mRNA for both IL-8 (neutrophil chemotactic peptide) and monocyte chemotactic protein. IL-1 stimulated synovial cells from both osteoarthritis and rheumatoid arthritis patients exhibited similar mRNA expression of interleukin-8 and monocyte chemotactic protein. A capacity to produce factors selectively chemotactic for neutrophils, lymphocytes and monocytes provides a mechanism whereby synovial cells can facilitate inflammatory arthritis.
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PMID:Interleukin-1 induced gene expression of neutrophil activating protein (interleukin-8) and monocyte chemotactic peptide in human synovial cells. 199 47

Interleukin-8 (IL-8), a cytokine with neutrophil chemotactic and activating properties, is known to be stimulated by IL-1. Fischer rats are more resistant to inflammation than Lewis rats probably due to a higher corticosteroid stress response. To determine the role of IL-8 in ocular inflammation, the effect of intravitreal injection of IL-8 was compared with that of IL-1 in both Lewis and Fischer rats. The IL-8, IL-1 alpha, or sterile balanced salt solution (control) was injected into one eye of each animal. Both IL-8 and IL-1 alpha caused inflammation in the eye of both strains, as detected by leukocyte counts of the anterior chamber and histopathologic examination. The eyes of animals injected with a cytokine had significantly higher numbers of leukocytes compared with eyes of control animals. Histopathologic examination confirmed these findings. The IL-1 alpha induced inflammation more consistently and more severely than the most effective dose of IL-8. This finding agreed with the concept of IL-1 initiating a cascade of inflammatory mediators including IL-8, which acts more specifically on a smaller population of leukocytes. A contralateral response was observed in the uninjected eye of experimental and control animals. The contralateral response in animals receiving the cytokines was significantly greater than that in controls. Lewis rats show a higher inflammatory response to the injections than do the Fischer rats. These data suggest that IL-8 may be active as one component in neutrophil-mediated ocular inflammation.
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PMID:Ocular inflammation stimulated by intravitreal interleukin-8 and interleukin-1. 201 35

Expression of the cytokine gene gro, also known as melanoma growth stimulatory activity, is induced by inflammatory stimuli, including IL-1. To determine whether gro expression is regulated at a post-transcriptional level, the effect of IL-1 on gro mRNA stability was examined. Treatment of fibroblasts with IL-1 beta caused a dose-dependent induction of gro mRNA. When IL-1 was withdrawn, gro mRNA decayed rapidly with a half life of 1 hour. This decay occurred whether or not actinomycin D was added to block new transcription. In contrast, when IL-1 was present in the medium, the level of gro mRNA was stable over 8 hours following addition of actinomycin D. In addition, the stability of a related mRNA, IL-8, was found to be regulated by IL-1. To examine whether Northern results reflected expression of gro alpha, or of the closely related genes, gro beta and gro gamma, RNA samples were analyzed by PCR. All three genes were found to be induced by IL-1 and all mRNAs were stabilized in the presence of IL-1. Northern analysis revealed a minor species of gro mRNA which lacked poly(A). The pattern of expression of this RNA suggested that it was a decay intermediate of one or more of the gro mRNAs. The findings indicate that mRNA stabilization is an important component of IL-1 induced gene expression.
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PMID:Post-transcriptional regulation of gro alpha, beta, gamma, and IL-8 mRNAs by IL-1 beta. 201 72

The histological features of biopsies from 18 previously unreported cases of Sweet's syndrome are reported. The dermal infiltrate in the majority of the cases contained numerous histiocytes that at first sight appeared to mimic neutrophils. The immunophenotype of these histiocytes was consistent with monocytes that have freshly infiltrated into the lesions. Only two of the cases in this series, associated with leukaemia, displayed the histological features of Sweet's syndrome with a predominant neutrophilic infiltration. We suggest that the initiating mechanisms in Sweet's syndrome are that monocyte/histiocyte-derived cytokines such as the interleukins IL-1 and IL-8, secreted either by infiltrating histiocytes in the non-leukaemia-associated cases of Sweet's syndrome or by tumoural myelomonocytic cells in those associated with leukaemia, are responsible for the systemic manifestations and the infiltration with neutrophils in the skin lesions.
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PMID:Histiocytes in Sweet's syndrome. 153 89

Human epidermal keratinocytes constitutively produce a variety of cytokines, including neutrophil chemotactic peptide named epidermal cell-derived thymocyte-activating factor, which has been later confirmed to be interleukin 1 (IL-1). Because recombinant IL-1 lacks chemotactic activity, in the present study, we examined the exact nature of the neutrophil chemotactic peptide in the culture supernatant of normal human epidermal keratinocytes. Normal human epidermal keratinocytes produced a neutrophil chemotactic factor, which was also chemotactic for T lymphocytes. Molecular sieve chromatography revealed an approximate molecular size of 11,000 daltons. The activity was retained after heating at 100 degrees C for 10 min, and at a pH between 4 and 11, but was partially inactivated at pH 3, or by trypsin treatment. The chemotactic activity was not inhibited by the treatment with anti-IL-1 antibody. Its production by keratinocytes was stimulated by IL-1 and lipopolysaccharide but not by UV irradiation, tumor necrosis factor-alpha or by interferon-gamma. The neutrophil chemotactic activity in vivo was confirmed by the intradermal injection of the factor into guinea pigs. Blocking study with monoclonal antibodies against NAP-1/IL-8 confirmed that the neutrophil chemotactic factor is IL-8.
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PMID:Normal human epidermal keratinocyte-derived neutrophil chemotactic factor. 207 75

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

Monocyte-derived neutrophil chemotactic factor (MDNCF)/IL-8, a novel cytokine, distinct from IL-1 and TNF was recently purified and cloned. This study was performed to investigate the biologic effect of recombinant MDNCF/IL-8 on human polymorphonuclear neutrophils (PMN) by assessment of their growth inhibitory activity against Candida albicans. The chemoattractant, FMLP was used as a positive control. We demonstrated that MDNCF/IL-8, similar to FMLP, effectively enhanced PMN-mediated anti-Candida activity. MDNCF/IL-8, from 1.0 to 1000 ng/mol, enhanced PMN-mediated anti-Candida activity, whereas FMLP was effective from 10(-10) to 10(-7) M. The optimal dose of MDNCF/IL-8 for PMN stimulation was 10 ng/ml which equalled the optimal chemoattractant dose. MDNCF/IL-8 itself, like FMLP, had no direct effect on Candida growth at any concentration and it stimulated antifungal activity only in PMN but not in monocytes. Interestingly, MDNCF/IL-8 failed to stimulate directly the production of superoxide from PMN or prime the respiratory burst of PMN exposed to FMLP. However, MDNCF/IL-8 was capable of releasing azurophilic enzymes from cytochalasin B-treated PMN into the extracellular space. Enhancement of PMN anti-Candida activity and release of azurophilic enzymes from PMN by MDNCF/IL-8 were inhibited in the presence of colchicine, which is a known inhibitor of degranulation. These results suggest that MDNCF/IL-8 induced antifungal action of PMN via oxygen-independent pathways. Furthermore, MDNCF/IL-8 induction of anti-Candida action by PMN was inhibited by pretreatment with Bordetella pertussis toxin, suggesting that enhancement of PMN antifungal activity by MDNCF/IL-8, as well as by FMLP, may be mediated by a GTP-binding protein.
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PMID:Functional activation of human neutrophils by recombinant monocyte-derived neutrophil chemotactic factor/IL-8. 215 63


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