UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapamycin (RPM) treatment prevents accelerated rejection of cardiac allografts in sensitized rats. The prominent feature of this brisk 24-h rejection, which includes a panoply of both cellular and humoral host immune responses, is a massive infiltration of rejecting grafts with neutrophils. In this study we tested the hypothesis that RPM-mediated therapeutic effects on accelerated rejection may be linked to decreased expression of protein encoded by gro/melanoma-growth stimulatory activity gene (KC) and macrophage inflammatory protein-2 (MIP-2) genes, the operational rat homologues of the human intercrine-alpha cytokines with proinflammatory IL-8-like neutrophil activation/chemotactic properties. The induction of these genes was then correlated with mRNA profiles encoding for Th1-selective IFN-gamma and CTL-specific granzyme B proteins. Northern blot analysis of RNA from cardiac allografts of sensitized untreated recipients, revealed maximal levels of KC and MIP-2 mRNA at 3 to 6 h after transplantation. In contrast, IFN-gamma mRNA, which was at most very weakly expressed at 3 h, peaked between 6 to 12 h. As with IFN-gamma, granzyme B transcripts were undetectable at 3 h, but peaked around the time of actual graft rejection at 24 h. RPM therapy abrogated accelerated rejection and prolonged cardiac allograft survival to ca. 46 days. This effect was associated with markedly reduced expression of KC and MIP-2 mRNA in the first 24 h as well as at 7 and 34 days after transplantation. Moreover, RPM completely blocked intragraft appearance of granzyme B and IFN-gamma mRNA in long term cardiac allografts. Immunohistologic analysis has revealed that accelerated rejection was associated with extensive neutrophil infiltration, which peaked at 18 to 24 h. At this time, leukocytes and endothelium were intensely stained for IL-8 and IFN-gamma antibodies. In contrast, the allografts from RPM-treated hosts showed essentially no neutrophil infiltration and minor, focal staining for IL-8 and IFN-gamma. This study demonstrates an association between the early expression of genes for proinflammatory IL-8-dependent neutrophil chemotactic activity, and later expression of genes associated with activation/effector activity of CTL and NK cells. It also documents a novel effect of RPM in vivo, which results in the suppression of intragraft IL-8-like and CTL-dependent mRNA/protein production and diminished neutrophil infiltration; these may contribute to the striking efficacy of RPM therapy in sensitized graft recipients.
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PMID:Rapamycin treatment depresses intragraft expression of KC/MIP-2, granzyme B, and IFN-gamma in rat recipients of cardiac allografts. 833 97

Polymorphonuclear neutrophils (PMN) have long been thought to be short-lived, terminally differentiated cells incapable of synthesizing significant levels of protein, with their primary function being phagocytosis and the release of cytotoxic compounds. More recently, it has been demonstrated that PMN can produce a number of functionally diverse substances, including IL-1, IL-6, and IL-8. Although PMN express class I MHC Ag, it has not been definitely demonstrated that they can synthesize and express class II Ag. This would suggest that, although PMN can indirectly assist in the induction of an immune response through production of cytokines, they are incapable of acting as APC for CD4+ Th cells. We show that, in the presence of a defined medium (AIM V), human serum, and granulocyte-CSF, nearly 100% of isolated PMN can survive for up to 2 days in vitro. We also show that PMN express MHC class II when present as bystander cells in a monocyte/T cell Ag presentation assay for 44 h. In addition, granulocyte/macrophage CSF (GM-CSF), IFN-gamma, and IL-3 can induce class II on pure cultures of PMN, with GM-CSF appearing to be the most potent of the three cytokines. Furthermore, induction of class II on PMN is distinctly donor dependent, with PMN from some donors repeatedly showing very high, and others very low, induction of class II when treated with GM-CSF. Their potential to express class II suggests that PMN could play a significant role in immunoregulation and disease pathogenesis. The variation in class II induction on PMN from individual donors might explain previous failures to detect class II induction on PMN and could be a factor in the varied susceptibility of different individuals to autoimmune and inflammatory disorders such as the production of antibodies to PMN cytoplasmic components.
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PMID:Induction of MHC class II on human polymorphonuclear neutrophils by granulocyte/macrophage colony-stimulating factor, IFN-gamma, and IL-3. 833 42

The production of interleukin-2 (IL-2) by phytohemagglutinin (PHA)-stimulated human leukemia T cell lines was significantly increased by 6 different cytokines. The most effective cytokines were interleukin-1 alpha (IL-1 alpha) and IL-1 beta; less effective were interferon-alpha (IFN-alpha), tumor necrosis factor-alpha (TNF-alpha), IFN-beta and TNF-beta. The combinations of two cytokines had synergistic or additive effects and increased IL-2 production to a greater extent than either cytokine alone. Other cytokines tested, such as IL-3, IL-4, IL-6, IL-7, IL-8 and IFN-gamma, had no effect on IL-2 production. However, a remarkable heterogeneity in sensitivity to the enhancing effects of the active cytokines was found among the IL-2-producing T cell lines studied. While IL-2 production in the most sensitive cell line, MOLT-16, was increased by all 6 active cytokines, other cell lines responded by increasing IL-2 production to stimulation with only some of the cytokines tested. The production of IL-2 in T cell line H9 was not enhanced by any of the cytokines used. These results show that several cytokines can increase IL-2 production by having a direct effect on the activated IL-2-producing T cells, but also that the outcome of the regulatory effects of individual cytokines depends considerably upon the individual IL-2-producing T cell clone.
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PMID:Enhancement of interleukin-2 (IL-2) production by 6 different cytokines: heterogeneity among IL-2 producing T cell clones. 834 81

IL-2 has pleiotropic properties and is a potent activator of monocytic functions. Since monocytes are an important source of the chemoattractant cytokine IL-8, we studied the effects of IL-2 on the expression of IL-8 in human monocytes. IL-8 mRNA expression was detectable in resting human monocytes. Treatment of monocytes with IL-2 increased IL-8 mRNA expression by a protein synthesis-independent process. The augmentation of IL-8 mRNA by IL-2 was associated with an increase in IL-8 secretion. The expression of IL-8 mRNA was not a nonspecific response to any stimulus of monocyte activation. In fact, IFN-gamma, which is also a potent monocyte activator, not only failed to induce IL-8 expression but inhibited the stimulation of IL-8 by IL-2. Nuclear run-on experiments demonstrated that both the enhancement of IL-8 mRNA expression and its down-regulation by IFN-gamma occurred at the transcriptional level. These results show for the first time that in fresh human monocytes, IL-8 expression is differentially regulated by IL-2 and IFN-gamma and suggest that the interactions among IL-2, IL-8, and IFN-gamma may be important for the development and control of the inflammatory response.
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PMID:IL-2 up-regulates but IFN-gamma suppresses IL-8 expression in human monocytes. 836 Apr 87

In order to evaluate the biological response after intraperitoneal administration of OK-432, we studied the changes of cytokine levels in ascitic fluid. In 6 advanced gastric cancer patients with peritoneal dissemination or extensive lymph node metastases, OK-432 20 KE was administered intraperitoneally during operation and the IL-6, IL-8 and IFN-gamma levels in ascitic fluid were measured from 0 to 5 postoperative days. These results were compared with those obtained from non-OK-432 administered control groups (17 cases). The ascitic level of IL-8 increased immediately after operation and gradually decreased. In the OK-432 treated group, the elevation of IL-8 on 0 and 1 postoperative days was remarkable, and there were statistically significant differences with the control group. Similarly, the ascitic level of IL-6 elevated soon after operation and then decreased gradually. In the OK-432 treated group, the ascitic level of IL-6 was significantly higher than in the control group after 3 postoperative days. There were no differences in changes of ascitic IFN-gamma levels between the groups. From these results, IL-6 and IL-8 appeared to be induced in ascitic fluid by intraperitoneal administration of OK-432.
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PMID:[Changes in cytokine levels in ascitic fluid after intraperitoneal administration of OK-432]. 837 2

To understand how expression of IL-8 mRNA is regulated, we studied the effects of Staurosporine, H7, phorbol-myristate-acetate and Dexamethasone in human neutrophils subsequently treated with IFN-gamma. Our results can be summarized as follows: a) IL-8 mRNA steady state levels were enhanced in a dose dependent fashion by both Staurosporine and phorbol-myristate-acetate, were not influenced by H7, but were decreased by Dexamethasone; b) the negative effect of IFN-gamma on IL-8 mRNA accumulation was prevented by Staurosporine and phorbol-myristate-acetate, was not influenced by H7, and was potentiated by Dexamethasone; c) IL-8 mRNA induction caused by Staurosporine was accompanied by a time and dose dependent release of IL-8 into the PMN supernatants.
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PMID:Studies on the regulatory mechanisms of interleukin-8 gene expression in resting and IFN-gamma-treated neutrophils: evidence on the capability of staurosporine of inducing the production of interleukin-8 by human neutrophils. 838 Dec 83

Gamma interferon (IFN-gamma) is the product of multiple cell types within the bone marrow microenvironment and has been demonstrated to act as a potent inhibitor of myelopoiesis in vitro and in vivo. The action of this cytokine on lymphohematopoiesis has now been examined on both long-term bone marrow cultures and representative cloned cellular components of the bone marrow microenvironment. In myelopoietic (Dexter) cultures, the half maximal inhibitory concentration of IFN-gamma was between 1 and 10 U/mL. In comparable lymphopoietic (Whitlock/Witte) cultures, IFN-gamma inhibited the production of B-lineage lymphoid cells with a half maximal effective concentration of less than 1 U/mL. In a clonal assay for pre-B cells, IFN-gamma inhibited colony formation with a half maximal concentration of 1 to 5 U/mL. Not all B-lineage lymphoid cells displayed the same sensitivity, however. Growth of the IL-7-dependent B cell line (2E8) in methylcellulose assays was unaffected by IFN-gamma while the replication of other lymphoid lines was partially or completely inhibited. IFN-gamma induced the expression of cell surface proteins (MHC Class I and II) on both B-lineage cells and stromal cells. In cloned stromal cell lines, IFN-gamma increased the steady state mRNA levels for the cytokines interleukin-6 (IL-6) and JE, a member of the IL-8 family. These data indicate that IFN-gamma acts within the lymphohematopoietic microenvironment through both direct and indirect actions on the hemopoietic and stromal cell populations.
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PMID:Modulation of lymphohematopoiesis in long-term cultures by gamma interferon: direct and indirect action on lymphoid and stromal cells. 842 61

After appropriate stimulation, mononuclear phagocytes express a specific inhibitor of interleukin (IL)-1, now re-named IL-1 receptor antagonist (IL-1ra). In this study we have examined the production of IL-1ra by polymorphonuclear cells (PMN). Human PMN isolated from peripheral blood expressed low but detectable levels of IL-1ra transcripts, which were considerably augmented after treatment with lipopolysaccharides (LPS) and cytokines [IL-4, granulocyte (G)- and granulocyte macrophage (GM)-Colony Stimulating factor (CSF), and tumor necrosis factor (TNF)]. The levels of induced IL-1 ra transcripts were comparable to those observed in endotoxin-stimulated human monocytes. By contrast IL-1 beta, interferon (IFN)-gamma and chemotactic factors (fMLP, C5a and IL-8) failed to promote IL-1ra expression in PMN. IL-1ra induction by LPS reached peak levels at 10 ng/ml after 3-6 h and remained sustained 24 h after stimulation. Induction by LPS and GM-CSF appears to be at the transcriptional level, as assessed by inhibiting mRNA synthesis with actinomycin D. Inhibition of protein synthesis by cycloheximide superinduced both basal and inducible IL-1ra mRNA. In addition to expressing mRNA, PMN also produce IL-1ra protein. Secretion of IL-1ra was induced in PMN treated with LPS, IL-4 and GM-CSF, but not by IL-1 beta, IFN-gamma and fMLP, thus yielding results that paralleled those seen in Northern blot experiments. These data indicate that, among myelomonocytic cells, PMN, in addition to mononuclear phagocytes, can express IL-1ra, suggesting that PMN, while exerting a series of pro-inflammatory activities, may also modulate the inflammatory potential of IL-1 in tissues.
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PMID:Expression of interleukin-1 receptor antagonist (IL-1ra) by human circulating polymorphonuclear cells. 843 89

The initiation and promulgation of chronic inflammation are controlled in part by the various pro-inflammatory and anti-inflammatory cytokines present at the site of injury. IFN-gamma and granulocyte-macrophage CSF (GM-CSF) are two cytokines that can contribute to the inflammatory state and possess both pro- and anti-inflammatory properties. However, the characterization of the interaction between GM-CSF-cultured monocytes and IFN-gamma is poorly documented. In this report we show that culture of human peripheral blood monocytes for up to 6 days in the presence of GM-CSF results in an eightfold increase in the level of IFN-gamma R expression, as determined by radioligand binding. The IFN-gamma R on these cells maintains a specificity typical of that observed in fresh monocytes. Only IFN-gamma, not IFN-alpha or -beta, blocks the binding of IFN-gamma to its receptor, and anti-IFN-gamma R antibodies block at least 80% of binding of IFN-gamma to these cultured cells. However, in spite of increased receptor expression, GM-CSF-cultured monocytes have a diminished response to IFN-gamma, as measured by the induction of the gene for IP-10 (a member of the platelet factor-4/IL-8 family). On the other hand, IFN-gamma-induced activation of the DNA-binding protein FcRF gamma is maintained in GM-CSF-cultured monocytes. Therefore, suppression of IFN-gamma-mediated IP-10 induction is not the result of a global abrogation of signal transduction across the IFN-gamma R but a more selective inhibition that appears to occur downstream of the receptor.
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PMID:Culture of human monocytes with granulocyte-macrophage colony-stimulating factor results in enhancement of IFN-gamma receptors but suppression of IFN-gamma-induced expression of the gene IP-10. 845 Feb 19

The aim of this study was to determine whether polymorphonuclear neutrophils (PMN) can modify the immune response in HIV cases. Supernatants of PMN (PMNS) from 33 HIV-infected patients (16 with lymphoadenopathy syndrome, 17 with AIDS-related complex) were tested for their influence on the functional activity of lymphocytes and monocytes from 6 healthy donors. PMNS from another 6 healthy donors comprised a control group. It was found that PMNS from HIV-infected patients, but not from healthy donors, induced suppression of lymphocyte proliferative response and down-regulation of CD8 receptor expression on lymphocytes. Decrease of NK-cell cytotoxicity in the presence of PMNS from HIV-infected patients was the same as that from healthy donors. PMNS did not influence the production of anti-HIV antibody by lymphocytes from HIV-infected patients, as well as non-specific IgG by lymphocytes from healthy donors. PMNS effect on functional activity of lymphocytes was blocked completely after treatment of PMN by catalase and superoxide dismutase. At the same time PMNS from HIV-infected patients but not from healthy donors induced increased production of TNF-alpha by monocytes and up-regulation of monocyte phagocytosis. These effects were independent of catalase and superoxide dismutase and were not abrogated by antibody against IL-1, IL-8, TNF-alpha, IFN-gamma or IFN-alpha.
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PMID:Modification of lymphocyte and monocyte functional activity by polymorphonuclear neutrophils in HIV infection. 846 29

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