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)

We investigated the response of purified and cloned human thymic epithelial cells (TEC) to IL-1, IL-4, and IFN-gamma stimulation in vitro. IL-1 alpha strongly up-regulated the production of granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), IL-6, and IL-8, as measured by specific immunoenzymetric assays and by increased steady state mRNA levels. IL-4 or IFN-gamma did not induce these cytokines in TEC but in a sustained and dose-dependent manner down-regulated the IL-1-induced GM-CSF protein and mRNA levels. Only IFN-gamma, and not IL-4, suppressed the IL-1-induced G-CSF and IL-8 production, as shown at both the protein and mRNA levels. The inhibition was dose dependent, sustained for at least 96 h, and more pronounced for G-CSF than for IL-8. In contrast, both IL-4 and IFN-gamma enhanced the IL-1-induced IL-6 production. IL-4 and IFN-gamma had additive effects to increase IL-6 secretion and to more completely suppress the IL-1-induced GM-CSF. Analyses of cell surface molecules showed that intercellular adhesion molecule 1 (ICAM-1) expression on TEC was increased by IL-1 or IFN-gamma. IL-4 slightly down-regulated constitutive ICAM-1 levels but did not significantly modify the levels of expression induced by either IL-1 or IFN-gamma. MHC class II expression was induced by IFN-gamma but not by IL-1 or IL-4. The combination of IL-1 and IL-4 with IFN-gamma did not alter the levels of class II MHC Ag induced by IFN-gamma. In conclusion, TEC cytokine production and cell surface molecule expression are differentially regulated via a complex cytokine network. Our data suggest that developing T cells provide, in part, the signals controlling the function of their supporting stroma.
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PMID:IL-1, IL-4, and IFN-gamma differentially regulate cytokine production and cell surface molecule expression in cultured human thymic epithelial cells. 171 90

Interleukin-8 (IL-8) stimulated an increase in cytoplasmic-free Ca2+ ([Ca2+]i) and intracellular pH (pHi) in parallel at low concentrations (0.5 to 5 ng/mL), and stimulated O2- release and membrane depolarization in parallel at high concentrations (50 to 5,000 ng/mL). IL-8-induced O2- release was potentiated by tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte-CSF (G-CSF) in a dose-dependent manner, whereas it was inhibited by cyclic AMP agonists. These characteristics and the time-courses of the responses stimulated by IL-8 were similar to those stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP), except that the cells stimulated by IL-8 showed shorter duration and less magnitude in some responses. In addition, IL-8 was found to be a potent priming agent and to enhance O2- release stimulated by FMLP. The priming effect of IL-8 was very rapid and was maximal within 5 minutes of preincubation. The dose-response curves for priming were identical to those for triggering of an increase in [Ca2+]i and pHi. The potency of the maximal priming effects on FMLP-induced O2- release was TNF greater than GM-CSF greater than IL-8 greater than G-CSF. The combination of IL-8 and the suboptimal concentrations of TNF or GM-CSF resulted in the additive priming effect, whereas the combination of the optimal concentration of IL-8 and the optimal concentration of TNF, GM-CSF, or G-CSF resulted in the effect of more potent priming agent alone. These findings suggest that IL-8 stimulates or primes human neutrophils according to its concentrations and cross-talks with TNF, GM-CSF, G-CSF, or FMLP at the inflammatory sites.
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PMID:Stimulation and priming of human neutrophils by interleukin-8: cooperation with tumor necrosis factor and colony-stimulating factors. 172 9

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

Human articular chondrocytes, when stimulated with interleukin 1 beta (IL 1 beta), tumor necrosis factor-alpha (TNF-alpha), or with the double stranded RNA poly (rI).poly (rC), produce a chemotactic activity for granulocytes. The induction with IL 1 beta could be abolished by an antibody to IL 1 beta but not by an antibody to interleukin 6 (IL 6), indicating that the latter is not a mediator for the production of chemotactic activity. The inducers had no direct chemotactic effect on granulocytes. The granulocyte chemotactic factor from chondrocytes was characterized with a specific antibody against leukocyte-derived interleukin 8 (IL 8). The specificity of this antibody was demonstrated by immunochemical and biological criteria such that it could immunoprecipitate only the 6-7 kDa IL 8 protein from fibroblasts, and that it did not neutralize a structurally related monocyte chemotactic protein. This antibody against IL 8 completely neutralized the granulocyte chemotactic activity from stimulated chondrocytes. This demonstrates the identity of chondrocyte IL 8 with leukocyte- and fibroblast-derived IL 8. Our data show that leukocyte chemotaxis into the inflamed joint can be mediated by IL 8, induced in both synovial fibroblasts and chondrocytes by the inflammatory cytokines IL 1 and TNF-alpha.
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PMID:Characterization of granulocyte chemotactic activity from human cytokine-stimulated chondrocytes as interleukin 8. 210 16

Current studies on IgE-dependent allergic reactions focus on the regulation of IgE synthesis by cellular IgE receptors or by their fragments, so-called IgE-binding factors. Recent studies suggest that lymphokines, such as interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), may be more relevant in the modulation of IgE synthesis. Under this aspect studies should concentrate on the role of anti-isotypical anti-IgE antibodies which can be found frequently in IgE-mediated responses. Further studies have given new insights in the variation of releasability and lymphokine-mediated conditioning of effector cells, depending on the type of allergic reaction. Pretreatment of neutrophils with granulocyte macrophage- colony stimulating factor (GM-CSF), or basophils with interleukin-3 (IL-3) renders these cells capable of producing or releasing inflammatory mediators, such as histamine, leukotrienes or platelet activating-factor (PAF). The fact that the interaction of purified lymphokines, such as IL-3 or IL-8 with basophils causes the release of mediators, indicates a possible mechanism for the induction of immediate and delayed allergic reactions. New insights in these mechanisms may offer new immunopharmacological aspects in the treatment of allergic reactions. IgE-mediated allergic reactions can be divided into two distinct phases. During the period of sensitization allergen exposure causes the production of class E immunoglobulins (IgE) in genetically predisposed persons. Repeated allergen exposure in sensitized persons leads to bridging of IgE molecules with basophils or mast cell membranes which finally causes the production and the release of inflammation mediators, such as histamine, leukotrienes and PAF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New perspectives in the modulation of allergic inflammation]. 213 73

Isolation of the human neutrophil activating protein (NAP) interleukin 8 (IL8) from leukocytes has revealed that it is structurally related to beta-thromboglobulin (beta TG) from platelets. Both these proteins occur as natural mixtures of multiple forms, differing from each other by unequal truncation at the NH2 terminus. In this study we have compared IL8 and beta TG forms for in vitro and in vivo neutrophil activation. In contrast to IL8, none of the beta TG forms were found to exert granulocyte chemotactic activity in vitro, as measured in the agarose assay. However, fractions rich in the most extensively processed forms of beta TG (e.g. NAP-2) as well as pure NAP-2 did induce lactoferrin release from granulocytes, whereas fractions containing only the longer forms (e.g. connective tissue-activating peptide III) were inactive. In order to observe this in vitro effect, about 10-fold less IL8 (10 nM) than NAP-2 was required. In the presence of a vasodilator substance low doses (2-20 pmol) of IL8 and the shorter forms of beta TG caused granulocyte accumulation and plasma leakage in rabbit skin whereas the longer forms of beta TG again failed to do so. Finally, granulocytosis induction following i.v. injection was found to occur with NAP-2. At the maximal dose tested (250 pmol), this in vivo effect of NAP-2 was less pronounced than that of IL8. In the case of IL8, NH2-terminal processing did not seem to affect granulocyte stimulatory activity. It should be noted, however, that the extent of processing of IL8 is less than that occurring with beta TG. It can be concluded that the platelet factor beta TG, structurally related to the monokine IL8, can also play a role in neutrophil activation during inflammatory reactions.
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PMID:The neutrophil-activating proteins interleukin 8 and beta-thromboglobulin: in vitro and in vivo comparison of NH2-terminally processed forms. 214 75

Stimulated human peripheral blood leukocytes produce a chemotactic factor for granulocytes (granulocyte chemotactic peptide/interleukin-8; GCP/IL-8), which is structurally related to platelet-derived beta-thromboglobulin. Analytically pure CGP/IL-8 and beta-thromboglobulin could be obtained after three purification steps, comprising adsorption to silicic acid, heparin-Sepharose chromatography and ion-exchange chromatography. Although GCP/IL-8 and beta-thromboglobulin had a similar affinity for heparin, they could be separated on a cation-exchange column. Both molecules were heterogeneous in that 6-7-kDa protein doublets were detected upon SDS/PAGE. N-terminal amino acid sequence analysis revealed the presence of six immunologically related but differently truncated polypeptides of beta-thromboglobulin, of which only two corresponded to previously described forms. Similarly, apart from a major polypeptide, five minor species of GCP/IL-8 were detected that also differed by N-terminal truncation. The most processed forms of beta-thromboglobulin and GCP/IL-8 were found to have their N-terminus in that region of the primary structure where a significant similarity between the two molecules starts. GCP/IL-8 was found to be chemotactic for granulocytes with a specific activity of 10(5) units/mg, whereas none of the beta-thromboglobulin species possessed detectable chemotactic activity.
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PMID:Purification of granulocyte chemotactic peptide/interleukin-8 reveals N-terminal sequence heterogeneity similar to that of beta-thromboglobulin. 252 1

So far, the role of fibroblasts in inflammatory processes has been underestimated. We have previously shown that stimulation of fibroblasts with viruses or bacteria results in a simultaneous production of several cytokines, including interferon-beta, interleukin (IL) 6 and colony-stimulating factors. We here report that virally infected fibroblasts produce also a chemotactic factor for granulocytes. The activity is inducible not only by measles virus but also by IL 1 beta and the double-stranded RNA poly(rI).poly(rC). This factor, when purified to homogeneity, occurs as a 6-7-kDa protein doublet upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The pure protein is serologically related to a fully characterized granulocyte chemotactic peptide (GCP) from monocytes, designated IL8. Furthermore, the chemotactic factor from fibroblasts has an NH2-terminal sequence identical to that of GCP/IL8, small differences in NH2-terminal processing being observed. Finally, in addition to diploid fibroblasts, the osteosarcoma MG-63 cell line is also a producer of GCP/IL8. It can thus be concluded that GCP/IL8 can be produced by several cell types in response to infection and that fibroblasts can contribute to chemotaxis in inflammation.
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PMID:The chemotactic activity for granulocytes produced by virally infected fibroblasts is identical to monocyte-derived interleukin 8. 266 11

The influence of human monocyte-derived chemotactic peptide (GCP/IL-8) on degranulation of neutrophils was investigated in relation to that of other monokines. GCP/IL-8 promoted a dose-dependent release of lactoferrin from specific granules but had no effect on enzyme release from primary granules. From the other monokines that were tested, tumour necrosis factor alpha (TNF alpha) also induced degranulation, while IL-1 beta and IL-6 scored negatively. TNF alpha-induced lactoferrin release was enhanced by cytochalasin B pretreatment of the granulocytes, while GCP/IL-8-promoted degranulation was not. In contrast to GCP, TNF alpha also caused the release of LDH, suggesting a non-specific cell destruction. These observations further support the view that, unlike the other monokines, GCP/IL-8 is a true and specific granulocyte activator.
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PMID:Human granulocyte chemotactic peptide (IL-8) as a specific neutrophil degranulator: comparison with other monokines. 267 Jul 52

Injection (i.v.) of the granulocyte chemoattractant/activator IL-8 has been shown to reduce neutrophil recruitment into dermal inflammatory sites in vivo. To further investigate the mechanism of this phenomenon, we examined the effect of i.v. [Ser-IL-8]72 (12-20 micrograms/kg) on leukocyte rolling and chemoattractant-induced emigration in mesenteric venules of New Zealand White rabbits and on expression of L-selectin (mAb LAM1-3) and CD18 (mAb 60.3) on circulating rabbit granulocytes. Within 1 min of IL-8 i.v., granulocytes virtually disappeared from carotid blood samples for approximately 5 min. Concomitantly, the flux of rolling leukocytes in mesenteric venules fell from 83 +/- 21 to 2 +/- 1 leukocytes/min. Both rolling leukocyte flux and systemic granulocyte count returned to or exceeded control values within less than 30 min. The chemoattractant/activator FMLP (0.15 microgram/kg i.v.) produced similar results. A second i.v. injection of IL-8 or FMLP, 90 min after the first challenge, had equipotent effects. Local extravascular application of IL-8 via micropipette close to a venule induced adhesion and emigration of 63 +/- 21 leukocytes per site before, but only 26 +/- 9 leukocytes per site 50 to 75 min after i.v. IL-8, when systemic granulocyte count and rolling leukocyte flux had reached or exceeded control values. This was not due to agonist-specific desensitization, because a similar reduction of leukocyte emigration was seen after FMLP i.v. Rabbit granulocytes circulating in vivo uniformly expressed near-control levels of L-selectin at all times between 3 and 360 min after IL-8 i.v. CD18 expression transiently increased after IL-8 i.v. and returned to base line by 90 min. These findings show that IL-8 i.v. reduces granulocyte recruitment to inflammatory sites by inhibiting function(s) necessary for transmigration that are independent of L-selectin and subsequent to rolling.
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PMID:Intravenous interleukin-8 inhibits granulocyte emigration from rabbit mesenteric venules without altering L-selectin expression or leukocyte rolling. 750 19


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