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)

Neither excitotoxic neurodegeneration nor lipopolysaccharide induces an acute myelomonocytic exudate in the murine central nervous system (CNS) parenchyma (Andersson, P.-B., V. H. Perry, and S. Gordon. 1991. Neuroscience, 42:201; Andersson, P.-B., V. H. Perry, and S. Gordon. 1992. Neuroscience 48:169). In this study formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, interleukin 8 (IL-8), IL-1, or tumor necrosis factor alpha were injected into the hippocampus to assess whether these leukocyte chemotaxins and known mediators of recruitment could bypass this block. They induced morphologic activation of microglia and widespread leukocyte margination but little or no cell exudation into the CNS parenchyma. By contrast, there was acute myelomonocytic cell recruitment to the choroid plexus, meninges, and ventricular system, comparable to that in the skin after subcutaneous injection. The normal CNS parenchyma appears to be a tissue unique in its resistance to leukocyte diapedesis, which is shown here to be at a step beyond chemotactic cytokine secretion or induction of leukocyte adhesion to cerebral endothelium.
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PMID:Intracerebral injection of proinflammatory cytokines or leukocyte chemotaxins induces minimal myelomonocytic cell recruitment to the parenchyma of the central nervous system. 161 59

Interleukin-8 (IL-8) is a potent proinflammatory cytokine known to be produced by several cell types. To elucidate whether endocrine cells can also make IL-8, we have tested supernatants from eleven thyroid follicular cell primary cultures. IL-8 was readily detected under basal conditions (range 3.4-32.1 ng/ml from 1 x 10(5) cells in 3 days) and was increased 4-20 fold by stimulation with IL-1. TSH and tumor necrosis factor had an inconsistent effect, while gamma-interferon reduced basal and IL-1-stimulated IL-8 production. Since IL-8 can act as a chemoattractant for lymphocytes, these observations may explain in part the accumulation of lymphocytes within the gland in autoimmune thyroiditis.
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PMID:Thyroid follicular cells produce interleukin-8. 161 27

Lipoarabinomannan (LAM), a major cell wall component of Mycobacterium tuberculosis, exhibits a wide spectrum of immunoregulatory effects. To identify cytokines produced by human PBMC in response to LAM, we used PCR amplification to detect cytokine mRNA. LAM-induced transcription of mRNA for cytokines characteristically produced by macrophages, including TNF, granulocyte-macrophage-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, and IL-10. In contrast, LAM did not induce transcription of mRNA for cytokines produced predominantly by lymphocytes, such as lymphotoxin, IFN-gamma, IL-2, IL-3, or IL-4. Measurement of concentrations of TNF, granulocyte-macrophage-CSF, IL-6, IL-10, IFN-gamma, IL-2, and IL-4 in cell culture supernatants indicated that cytokine release correlated with mRNA patterns. Lipomannan (LM) and phosphatidylinositol mannosides (PIM) are simpler versions of LAM. LM lacks arabinan, whereas PIM lacks both arabinan and most mannan residues. LAM, LM, and PIM induced transcription of cytokine mRNA, elicited cytokine production, and suppressed Ag-induced T cell proliferation, indicating that most of the biologic activity of LAM was associated with the phosphatidylinositol end of the molecule. In support of this conclusion, deacylation of LAM abrogated its capacity to induce cytokine production and suppress Ag-induced proliferation. The production of macrophage-derived cytokines induced by LAM may mediate clinical manifestations of tuberculosis such as fever, weight loss, and tissue necrosis, as well as immunoregulatory effects such as inhibition of Ag-induced proliferation and hyperglobulinemia.
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PMID:Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. 162 1

Tumour necrosis factor-alpha (TNF-alpha) is a pivotal cytokine at the centre of a cascade of cytokines and inflammatory mediators which modulate the host response to infection and trauma, and in particular the metabolic changes resulting in shock and subsequent multi-organ failure. The cytokine IL-8--predominantly an activator and chemotactic factor for circulating polymorphonuclear neutrophil leucocytes--is produced in response to TNF-alpha in vitro, and high circulating levels of IL-8 are found in septic primates. We have studied the release of IL-8 into the circulation of subjects with chronic hepatitis B undergoing a 10 week pilot trial of recombinant TNF-alpha (rTNF-alpha) therapy in doses of 15-100 micrograms/m2. A marked dose-dependent increase in plasma IL-8 levels was seen commencing at 30-60 min after the start of rTNF-alpha infusion and peaking between 2 and 3 h (mean peak level 4300 ng/l). The temporal pattern of IL-8 production exactly echoed that of IL-6, another component of the cytokine cascade, but peak plasma levels of IL-8 were up to 17 times higher than those of IL-6. This study confirms in vitro data suggesting that IL-8 is a component of the acute circulating cytokine cascade with a potential role in the modulation of the acute immune and metabolic response to infection and trauma.
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PMID:IL-8 as a circulating cytokine: induction by recombinant tumour necrosis factor-alpha. 162 17

Cells expressing messenger RNA (mRNA) for inflammatory cytokines [interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-8] were demonstrated by in situ hybridization in human inflamed gingiva. When this technique was used in conjunction with immunohistochemistry, IL-1 alpha and/or beta and IL-8 messages were observed predominantly on macrophages infiltrating the gingiva. TNF-alpha messages were abundant on macrophages and T cells. In contrast, the IL-6 mRNA were more widely distributed on many types of cells such as macrophages, T cells, fibroblasts, endothelial cells and B cells. This study clearly identified the cells which express mRNA for inflammatory cytokines in inflamed gingiva and suggested an involvement of cytokine network in the generation of human periodontitis.
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PMID:Detection of inflammatory cytokine messenger RNA (mRNA)-expressing cells in human inflamed gingiva by combined in situ hybridization and immunohistochemistry. 162 99

Interleukin-8 (IL-8) induces diverse biological responses in neutrophils, including inhibition of adhesion to cytokine-activated endothelium, which we have termed the leukocyte adhesion inhibition (LAI) effect. Pretreatment of neutrophils with cytochalasin B abolished the LAI effect of IL-8, suggesting a microfilament-dependent mechanism. Interleukin-8 induced a rapid increase (less than or equal to 15 s) in the polymerization of actin filaments in human neutrophils that was blocked by pretreatment with cytochalasin B. F-actin depolymerization occurred gradually at a rate inversely proportional to IL-8 concentration. This temporal pattern of actin polymerization-depolymerization was similar to that induced by other chemotactic factors such as C5a and N-formylmethionyl-leucyl-phenylalanine, which also exhibit a marked LAI effect, but the lipid mediators, leukotriene B4 and platelet-activating factor, lack any significant LAI effect. Scanning confocal microscopy demonstrated that neutrophil actin microfilaments undergo a dramatic rearrangement prior to detachment of the neutrophil from a surface. We suggest that the ability of IL-8 and certain other leukocyte agonists to regulate the actin polymer network of neutrophils may play an important role in adhesive interactions with the vascular endothelium.
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PMID:Interleukin-8 induces changes in human neutrophil actin conformation and distribution: relationship to inhibition of adhesion to cytokine-activated endothelium. 164 Jan 74

Human interleukin 5 (IL-5), known as a selective colony-stimulating factor of the eosinophil lineage and activator of mature eosinophils, also profoundly influences the mediator release profile of human basophils. IL-5 by itself triggers neither granule release nor de novo synthesis of lipid mediators. However, at low concentrations (0.1-10 ng/ml), IL-5 rapidly primes basophils for enhanced histamine release and leukotriene C4 (LTC4) generation in response to all established basophil agonists. LTC4 generation is more strongly affected by IL-5 than histamine release. In particular, IL-5 renders basophils capable of producing large quantities of LTC4 in response to C5a, which, without the cytokine, induces histamine release only. Finally, IL-5 renders basophils responsive to agonists (neutrophil-activating peptide 1 and C3a), which are otherwise inefficient triggers for basophil mediator release. The effects are similar to the recently established bioactivity of IL-3 on basophils, with the exception of its influence on IgE-dependent basophil activation, which is less pronounced. Thus, IL-5 strongly modulates the function not only of eosinophils but also of basophils, the two major effector leukocyte types involved in allergic inflammatory processes, e.g., in asthma.
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PMID:Interleukin 5 modifies histamine release and leukotriene generation by human basophils in response to diverse agonists. 170 20

The importance of immunologic mechanisms in psoriasis has been deduced from the ability of immunosuppressive therapies to ameliorate this common and chronic skin disease. Certainly the histology of psoriatic lesions suggests a dialogue between the hyperplastic keratinocytes and infiltrating T lymphocytes and macrophages. To begin dissecting the cytokine network involved in the pathophysiology of psoriasis, the location, in both epidermal and dermal compartments, of tumor necrosis factor-alpha, interleukin-8, intercellular adhesion molecule-1, and transforming growth factor-alpha at the protein and/or mRNA levels were identified. Tumor necrosis factor-alpha was selected as a potentially key regulatory cytokine, first because it induces cultured keratinocyte interleukin-8, intercellular adhesion molecule-1, and transforming growth factor-alpha production, and second because intercellular adhesion molecule-1 expression by keratinocytes in psoriatic epidermis had been identified previously. Using immunohistochemical localization, tumor necrosis factor-alpha was identified in 12 psoriatic lesions as intense and diffuse expression by dermal dendrocytes (macrophages) in the papillary dermis (without significant staining of endothelial cells, mast cells, or dermal Langerhans cells), and focally by keratinocytes and intraepidermal Langerhans cells. Functional interaction between the dermal dendrocytes and keratinocytes was suggested by the presence of interleukin-8 expression of suprabasal keratinocytes immediately above the tumor necrosis factor-alpha-positive dermal dendrocytes. Interleukin-8 mRNA and transforming growth factor-alpha mRNA were detectable in the epidermal roof of psoriatic lesions, but neither was detectable at the protein or mRNA levels in any normal skin specimens. Treatment of cultured human keratinocytes with phorbol ester (which experimentally produces psoriasiform changes on mouse skin) or tumor necrosis factor-alpha also increased interleukin-8 and transforming growth factor-alpha mRNAs. Further elucidation of the cellular and molecular basis for the genesis and evolution of psoriasis will provide the framework for a better evaluation of the cause and treatment of this skin disease.
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PMID:Cellular localization of interleukin-8 and its inducer, tumor necrosis factor-alpha in psoriasis. 170 29

In order to better understand the factors regulating disease promotion and activity in psoriasis (PS), we searched for the in situ expression of mRNA for various cytokines in long-standing PS skin lesions. Specific hybridization with a NAP-1/IL-8 anti-sense RNA probe was keratinocyte associated and yielded strong and specific signals exclusively in the upper layers of the lesional epidermis, but not in uninvolved skin from psoriatic patients or normal skin from non-psoriatics. Interestingly, NAP-1/IL-8 transcripts were focally clustered in a spotty pattern predominantly between the tips of elongated papillae, but were absent in the lower epidermal region and the dermal compartment. We consistently failed to detect appreciable numbers of TNF-alpha and/or IL-6 mRNA-containing cells in psoriatic lesions. These results support the notion that IL-8, rather than IL-6, is an important disease-promoting cytokine in PS. In view of the known in vitro and in vivo effects of IL-8, it is conceivable that this substance greatly contributes to the major pathologic changes seen in psoriatic skin, i.e., keratinocyte hyperproliferation and leucocyte infiltration. In this case, local pharmacologic down-regulation of NAP-1/IL-8 activity could be a promising therapeutic strategy in PS.
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PMID:Upper keratinocytes of psoriatic skin lesions express high levels of NAP-1/IL-8 mRNA in situ. 171 50

Macrophages and monocytes have essential roles in normal wound healing, in the immune response, and in the pathogenesis of atherosclerosis. Platelet-derived growth factor (PDGF) stimulates the transcription of the early response gene, JE, and its human homolog, macrophage chemotactic protein-1 (MCP-1) in fibroblasts. JE/MCP-1 encodes a cytokine which is a member of a superfamily of small inducible genes that include platelet factor 4, beta-thromboglobulin, 310-C/NAP-1/IL-8, IP-10, KC/gro/MGSA, and others which may play important roles in the inflammatory and immune response. We now report that glucocorticoids inhibit the transcriptional induction of the JE gene by PDGF and serum in a dose-dependent manner. The glucocorticoid response followed the expected anti-inflammatory rank order of potency and was not due to a shift in the time course of induction. Nonsteroidal anti-inflammatory agents were ineffective in reducing JE mRNA levels. Dexamethasone inhibited the accumulation of JE transcripts induced by PDGF, 12-O-tetradecanoylphorbol-13-acetate, and double-stranded synthetic RNA. Nuclear runoff assays demonstrated that the negative regulation occurred by decreasing the transcriptional induction of the JE gene. No effects on JE message stability could be detected in the presence of dexamethasone. The protein synthesis inhibitors cycloheximide and puromycin reversed the glucocorticoid-mediated inhibition and suggested that new protein synthesis was necessary. These results suggest that the transcriptional inhibition of glucocorticoids is mediated by the expression of a labile transcriptional repressor for the JE gene.
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PMID:Glucocorticoids inhibit the transcriptional induction of JE, a platelet-derived growth factor-inducible gene. 171 76


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