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)

Activation of human monocytes with LPS induces coordinate expression of a number of cytokine genes, including IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, and IL-8. The T cell-derived lymphokine, IL-4, inhibits expression of these genes in monocytes, suggesting that it may be an important physiologic regulator of cytokine production. We have previously shown that IL-4 reduces steady state messenger RNA (mRNA) levels for IL-1 beta in human monocytes by decreasing both IL-1 beta transcription and the t1/2 of newly formed IL-1 beta mRNA transcripts. In the present study, we extend these findings to show that IL-4 similarly accelerates the turnover of IL-6 mRNA in LPS-stimulated monocytes. However, this inhibition of cytokine expression and dramatic increase in the decay rate of cytokine mRNA does not extend to all LPS-inducible genes because IL-4 treatment did not inhibit the expression or accelerate the turnover of mRNA for the IL-1 receptor antagonist (IL-1ra) in the same cells. Although IL-1 beta and IL-1Ra are both LPS-inducible genes, they displayed distinct temporal patterns of expression. Peak steady state mRNA levels for IL-1ra lagged significantly behind that of IL-1 beta, suggesting a possible endogenous mechanism for limiting IL-1 biologic activity. Furthermore, although IL-4 suppressed expression of both IL-1 beta and IL-6, it up-regulated synthesis of IL-1ra mRNA and protein. Thus, IL-4 inhibits production of the proinflammatory cytokine, IL-1 beta, while concomitantly enhancing synthesis of the IL-1ra in activated human monocytes.
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PMID:IL-4 reciprocally regulates IL-1 and IL-1 receptor antagonist expression in human monocytes. 138 62

Neutrophils, an abundant cell type at sites of inflammation, have the ability to produce a number of cytokines, including interleukin 1 (IL-1), IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha). In this study, we have examined the ability of human neutrophils to produce the IL-1 receptor antagonist (IL-1Ra), a 17-23-kD protein recently isolated and cloned from macrophages. Since IL-1Ra has been shown to inhibit both the in vitro and in vivo effects of IL-1, its production by large numbers of tissue-invading neutrophils might provide a mechanism by which the effects of IL-1 are regulated in inflammation. Using antibodies that are specific for IL-1Ra and a cDNA probe encoding for this protein, we were able to show that neutrophils constitutively produce IL-1Ra. However, after activation by GM-CSF and TNF-alpha, IL-1Ra was secreted into the extracellular milieu where it constituted the major de novo synthesized product of activated neutrophils. None of a large array of other potent neutrophil agonists were found to affect the production of IL-1Ra by neutrophils. Quantitative measurements by enzyme-linked immunosorbent assay revealed that intracellular IL-1Ra is in eightfold excess of the amount secreted in supernatants when studying nonactivated neutrophils. However, in GM-CSF- and TNF-alpha-activated cells, this difference was reduced to values between four- and fivefold, as virtually all of the de novo synthesized IL-1Ra was secreted. In activated cells, the intracellular content of IL-1Ra was found to be in the 2-2.5-ng/ml range per 10(6) neutrophils, whereas levels reached the 0.5-ng/ml range in supernatants. This would imply that IL-1Ra is produced in excess of IL-1 by a factor of at least 100, an observation that is in agreement with the reported amounts of IL-1Ra needed to inhibit the proinflammatory effects of IL-1. Neutrophils isolated from an inflammatory milieu, the synovial fluid of patients with rheumatoid arthritis, were found to respond to GM-CSF and TNF-alpha in terms of IL-1Ra synthesis, indicating that the in vitro observations made in this study are likely to occur in an inflammatory setting in vivo.
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PMID:Human neutrophils produce high levels of the interleukin 1 receptor antagonist in response to granulocyte/macrophage colony-stimulating factor and tumor necrosis factor alpha. 138 77

A superficial peripheral lymph vessel draining the skin of the upper and medial part of the foot was cannulated on the lower leg of six healthy human volunteers. After 2 days an irritant contact dermatitis was induced by application of 10% sodium lauryl sulphate to the area of skin drained by the lymph vessel. Three days later the spontaneously regressing skin reaction was treated with clobetasol propionate. Lymph was collected twice daily for 7 days, and the levels of various cytokines (IL-1 alpha, IL-1 beta, IL-2 and soluble IL-2 receptors, IL-6, IL-8, TNF-alpha, GM-CSF) were determined by ELISA technique. In the majority of the volunteers all cytokines examined were detected in several lymph samples, with the exception of IL-1 alpha and IL-8. In parallel with the clinical symptoms of the contact dermatitis the levels of IL-6 and TNF-alpha increased 8-10-fold, whereas for IL-1 beta, IL-2, IL-2 receptors, and GM-CSF there was a delayed, 2-3-fold increase. These results suggest that cytokines, in particular IL-6 and TNF-alpha, may actively participate in the immunological reactions in the skin and in the regional lymph nodes during contact dermatitis.
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PMID:Increased levels of inflammatory cytokines in human skin lymph derived from sodium lauryl sulphate-induced contact dermatitis. 139 Jan 70

Interleukin-8 (IL-8) exerts unique chemotactic and activating activity on neutrophils. To address the significance of IL-8 in the fetoplacental unit during pregnancy, we cultured human placental explants that had been obtained by vaginal delivery, Caesarean section, or artificial abortion and then measured the IL-8 titer in the culture supernatants by enzyme immunoassay (EIA). Chorionic tissue from the first trimester produced a significant amount of IL-8 (2.2 +/- 0.4 ng/ml/10 mg, n = 5), while placentae in the second trimester (8.3 +/- 1.6 ng/ml/10 mg, n = 7) or at term (9.2 +/- 0.7 ng/ml/10 mg, n = 29) produced significantly higher amounts of IL-8. The presence or absence of labor did not affect the amount of placental IL-8 production. However, placentae with chorioamnionitis (25.2 +/- 1.6 ng/ml/10 mg, n = 9) showed significantly higher IL-8 production than those without chorioamnionitis (p less than 0.0001). Northern blot analysis of IL-8 mRNA expression demonstrated a constant level during pregnancy with or without chorioamnionitis, indicating the possibility that the major site of regulation of IL-8 synthesis in the placenta is posttranscriptional. Immunohistochemical analysis of first and third trimester placental tissues with rabbit anti-IL-8 antibody revealed the IL-8 producing cells to be trophoblasts and macrophage-like cells. IL-8 produced by the placental cells might contribute to potentiation of the immunocompetence of placental cells against bacteria invading the fetoplacental unit.
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PMID:Human placenta constitutively produces interleukin-8 during pregnancy and enhances its production in intrauterine infection. 139 27

Expression of the C3 receptors CR1 and CR3 was investigated on neutrophils from paired peripheral blood and synovial fluid samples from 34 patients with inflammatory joint disease (21 patients with rheumatoid arthritis (RA) and 13 patients with other articular diseases (OAD)). Using monoclonal antibodies (anti-CD35, anti-CD11b) and immunofluorescence flow cytometric analyses the percentages of positively labeled cells and the relative fluorescence intensities (as a measure of receptor number) were determined. CR1 and CR3 were found to be present on the majority (> 85%) of circulating neutrophils from normal subjects, RA and OAD patients, and on synovial fluid neutrophils from both patient groups. A strong correlation between neutrophil CR1 and CR3 expression was observed in peripheral blood samples from normal subjects (r = 0.81; P = 0.001), RA (r = 0.79; P = 0.001), and OAD patients (r = 0.83; P = 0.001); in each case the levels of CR3 expression were approximately twice those recorded for CR1. Both CR1 and CR3 expression was upregulated on synovial fluid neutrophils compared with that observed on the corresponding peripheral blood cells. Mean percentage increases observed were: RA patients: CR1, 16.5% (P < 0.001) and CR3, 28.7% (P < 0.001); and OAD patients: CR1, 4.1% and CR3, 26.9% (P = 0.001). Correlation of serum and synovial fluid IL-6, IL-8, and immune complex levels with neutrophil CR1 and CR3 expression failed to demonstrate any significant relationship between the concentrations of these soluble factors and receptor expression. Upregulation of CR1 and CR3 receptors, reflecting neutrophil activation within the inflamed joint, is a consistent finding in patients with inflammatory arthropathies.
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PMID:Markers of inflammatory activation: upregulation of complement receptors CR1 and CR3 on synovial fluid neutrophils from patients with inflammatory joint disease. 139 30

In preterm deliveries, we have reported a high incidence (30-50%) of histologic chorioamnionitis (CAM) in the placenta. There is little evidence about the effects of CAM on preterm infants. We investigated the levels of complements and cytokines in the cord blood, the pathological nature of the placenta, the L/S ratio of gastric and tracheal aspirate of each preterm infant at birth, and assessed the biological effects of CAM on them. CAM stimulates the immunological system by cytokine production (IL6 and IL8) and complement activation in the fetus. It has been suggested that CAM may be one of the factor accelerating fetal maturation of the immunological system such as complement activation and immunoglobulin production, and of surfactant synthesis in the lung. On the contrary, CAM may damage the structures along the lining cells in the airway by accumulating polymorphonuclear cells of the infants with Wilson-Mikity syndrome.
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PMID:Significance of chorioamnionitis. 139 24

We have examined the Hodgkin's disease derived cell line Co in terms of its capacity to differentiate in vitro. Co cells show the characteristics of immature T cells and express CD3 molecules in the cytoplasm. On activation with 12-O-tetradecanoylphorbol-13-acetate (TPA) these cells express the CD3 antigen and the T cell receptor alpha beta (TCR alpha beta) on the cell surface. Surface expression of the activation marker CD25 (IL2 receptor) was also greatly increased, whereas CD4 and CD8 levels were not altered. Supernatants of TPA-stimulated Co cells contained the cytokines IL2, IL3, IL4 and IL8, whereas these cytokines were not detected in the supernatants of untreated cells. Different subclones of the Co cell line differed in their response to TPA with respect to the induced CD3 and TCR expression. Our data demonstrate that a Hodgkin's disease derived cell line can be induced to differentiate in vitro from a pre-T cell phenotype towards a more mature T cell. It is possible that similar processes may occur in Hodgkin's disease in vivo.
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PMID:In vitro differentiation of a Hodgkin's disease derived cell line. 139 15

The synovial fluid aspirated from patients with symptomatic arthritis was analyzed for the presence of tumor necrosis factor (TNF), interleukin 6 (IL-6) and interleukin 8 (IL-8). All three cytokines were found in both inflammatory and non-inflammatory arthritides: IL-8 levels ranged from less than 20 to 38,990 pg/ml, IL-6 from less than 10 to 72,300 pg/ml and TNF from less than 4 to 61 pg/ml. No inhibitors of cytokine activity were found. IL-8 and IL-6 were present in significantly higher levels in patients with inflammatory arthritis compared to patients with osteoarthritis, and there was significant correlation between the IL-6 and IL-8 levels. These findings document the presence of multiple cytokines in the synovial fluid specimens of patients with arthritis, and demonstrate that higher cytokine levels accompany inflammatory arthritis.
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PMID:Profile of cytokines in synovial fluid specimens from patients with arthritis. Interleukin 8 (IL-8) and IL-6 correlate with inflammatory arthritides. 139 81

We have investigated the effects of a novel neutrophil-activating factor released by Trichomonas vaginalis (TV-NAF) on neutrophil chemotaxis. TV-NAF was present in the supernatant from 10(7) T. vaginalis (STV) cultured in 1 ml of serum-free Hanks' balanced salt solution (HBSS) at 37 degrees C for 30 min. With a multichamber chemotactic assay, we found that there were 112 +/- 15 migrated neutrophils (mean +/- standard deviation, n = 7) for STV and 11 +/- 4 for HBSS per high-power field (x 400). STV was also able to induce neutrophil actin assembly (increased 1.5-fold), enhance expression of complement receptor type 3 (increased 5-fold), and promote intracellular calcium mobilization (increased 2.5-fold). There was no chemotactic activity in the preparation of STV from killed trichomonads. The fact that heating up to 100 degrees C or deproteinization by treatment with proteinase K at 65 degrees C for 1 h did not abolish its chemotactic activity suggests that the TV-NAF involved was not a protein. The chemotactic activity of TV-NAF was associated with the fraction containing small molecules of less than 3,000 Da. Therefore, the possibility that eicosanoid production by trichomonads is responsible for neutrophil activation was investigated. Leukotriene B4 (LTB4; 500 pg/ml) but not thromboxane B2 (< 20 pg/ml) or prostaglandin E2 (< 8 pg/ml) was found in the STV by radioimmunoassay. Production of LTB4 by trichomonads was time dependent and increased twofold when arachidonic acid (100 microM) was added but was not decreased when eicosanoid inhibitors were present. Evidence for the presence of LTB4 in STV was further provided by the fact that rabbit anti-LTB4 antiserum could abolish the chemotactic activity of STV. These studies suggest that the spontaneous release of TV-NAF, which is most likely LTB4, may activate neutrophils, presumably through a different arachidonate metabolic pathway than that in mammalian cells.
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PMID:A novel neutrophil-activating factor released by Trichomonas vaginalis. 139 62

Interleukin-1 (IL-1) is a 17-kDa pro-inflammatory cytokine synthesized from a variety of cell types primarily in association with disease states or during host perturbation such as immune responses. At pM or even fM concentrations, IL-1 triggers various responses in nearly all cells. It appears that there is little or no major role for IL-1 in homoeostatic mechanisms. There are two IL-1's (alpha and beta) each with its distinct sequence; there are two IL-1 receptors. Disease states such as local and systemic infection, septic shock, degenerative arthritis and autoimmune diseases such as nephritis, vasculitis and inflammatory bowel disease appear to be mediated, in part, by IL-1. Organ failure, capillary leak and death occur in animals after a combination of tumour necrosis factor (TNF) and IL-1 which is more effective in inducing these changes than either cytokine alone. IL-1 is also a potent inducer of endothelial cell adhesion molecules, IL-6, and IL-8, a neutrophil chemotactic and activating factor. Strategies for reducing the effects of IL-1 have been based on suppression of transcription, translation, or secretion; more recently, receptor blockade has been a new approach. A naturally occurring IL-1-specific receptor antagonist (IL-1ra), which shares 40% conserved amino-acid homology with IL-1 beta, binds to IL-1 surface receptors with the same affinity as IL-1 but does not possess agonist activity and acts as a competitive inhibitor of IL-1. Studies using the IL-1ra to block endogenous IL-1 in a variety of animal disease models suggest that IL-1 plays a key role in triggering the cascade of inflammatory responses. In addition, the IL-1ra reduces the spontaneous production of growth factors and proliferation of leukaemic cells. The IL-1ra may be an advantageous therapy in patients with sepsis, diabetes, inflammatory bowel, arthritis and cancer.
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PMID:Reduction of inflammation by decreasing production of interleukin-1 or by specific receptor antagonism. 139 23


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