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)

The processes of lymphocyte-endothelial cell interaction and the in vitro assays employed in their study are the subjects of this review. In motility assays in porous filters and gel matrices, it has been shown that lymphocyte migration can be modulated by interleukin-2 (IL-2), IL-3, IL-4, IL-6, and IL-8. Cytokines can also modulate lymphocyte-endothelial adhesion. Endothelial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) are induced or upregulated by IL-1 or tumor necrosis factor. In addition, interferon-gamma upregulates ICAM-1, and IL-4 can induce VCAM-1. The roles of these cytokines and adhesion molecules in transendothelial migration may be studied in assays in which lymphocytes penetrate layers of cultured endothelial cells. These models can distinguish lymphocyte adhesion from subsequent migration. Using such models, we and others have obtained evidence that both lymphocyte function-associated antigen-1 (LFA-1)/ICAM-1 and very late activation antigen 4 (VLA-4)/VCAM-1 interactions mediate lymphocyte adhesion to endothelial cells, but that LFA-1/ICAM-1 interactions play a greater role in transendothelial migration.
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PMID:In vitro models of lymphocyte transendothelial migration. 138 72

The present study was undertaken to assess the effects of interleukin-1 beta (IL-1 beta) and interleukin-2 (IL-2) on glial and neuronal cells in culture. The presence of IL-1 beta-like and IL-2-like immunoreactivity was detected in media collected from both astroglial and microglial cultures, indicating that both lymphokines can be released from either cell type. However, the levels measured in microglial media were significantly higher than in the astroglial media. Moreover, the content of IL-1 beta-like immunoreactive material in the media was approximately five-to 10-fold greater than that of IL-2, although exposure of both microglial and astroglial cultures to IL-1 beta significantly enhanced this measure. A possible role for this glial-derived IL-1 beta as an astroglial growth factor was substantiated by experiments showing that the lymphokine increased the incorporation of [3H]thymidine into astroglial, but not microglial cultures. In contrast, IL-2 did not significantly alter glial proliferation. In hippocampal neuronal cultures, these lymphokines affected neuronal survival differently. Thus, only the highest concentration (500 ng/ml) of IL-1 beta tested decreased the long-term (three day), but not the short-term (one day), survival of these neurons, whereas neuronal survival was compromised by IL-2 even after short-term (one day) exposure. In addition, in the long-term (three-day-old) neuronal cultures exposed to IL-2, extensive cellular swelling, vacuolations and neurite retractions were noted, even in cultures exposed to relatively low concentrations (< 10 ng/ml) of the lymphokine. These effects were not apparent with IL-1 beta or the other lymphokines tested, including IL-3, IL-4 and IL-8. The results suggest that the glial-derived lymphokines IL-1 beta and IL-2 may have different functions in the CNS. Whereas IL-1 beta may have an important role in the developing brain as a maintenance and growth-promoting factor, IL-2 may function as an inhibitory factor, and may be of significance only in instances during which it accumulates in sufficiently high concentrations in the vicinity of neurons.
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PMID:Differential effects of interleukin-1 beta and interleukin-2 on glia and hippocampal neurons in culture. 757 76

Human natural killer cells (NK) respond to interleukin-2 (IL-2) with augmented cytolytic activity, cytokine secretion and cell proliferation. Here we show that IL-2 protects NK cells from death by apoptosis (programmed cell death; PCD). Highly purified NK cells (CD3- CD56+) were isolated from peripheral blood lymphocytes (PBL) of either control donors or of an asymptomatic donor with 60% NK cells. Glucocorticosteroids (GCS) induced PCD in NK cells, as shown by nuclear condensation and DNA fragmentation. IL-2 completely prevented GCS-induced PCD in a dose-dependent manner without overcoming GCS-induced inhibition of NK cell proliferation. The IL-2 protective effect was mediated through the p75 beta chain of the IL-2R, as neutralizing monoclonal antibody (mAb) to the p75 beta chain but not to the p55 alpha chain completely abolished the IL-2 anti-apoptotic activity. In addition to IL-2, the cytokines IL-7 and IL-12 have been reported to regulate NK cell functions. Our present data showed that IL-7 but not IL-12 rescued NK cells from apoptosis, but to a lesser extent than IL-2. Although IL-4 had a marginal protective effect, IL-1, IL-3, IL-6, IL-8, interferon-gamma (IFN-gamma) and IFN-alpha, tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte-macrophage colony-stimulating factor (GM-CSF) displayed no significant activity. Finally, we report that IL-2 and IL-7 enhanced bcl-2 expression in NK cells, suggesting the existence of a bcl-2-dependent survival pathway. In addition to regulating various functions, it is concluded that IL-2 and IL-7 have the ability to prevent PCD in NK cells.
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PMID:IL-2 and IL-7 but not IL-12 protect natural killer cells from death by apoptosis and up-regulate bcl-2 expression. 764 25

Inflammatory malignant fibrous histiocytomas (IMFH) are rare tumors and are frequently associated with leukocytosis. In rare cases, leukemoid reactions were attributed to tumor production of unidentified hematopoietic factors. In this study, we used immunohistochemical techniques to show cytokine immunoreactivity in the malignant cells of two cases of IMFH presenting with leukemoid reactions and compared them with two malignant fibrous histocytomas, noninflammatory type. All four tumors stained positively for stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-2 (IL-2), IL-4, IL-5, interferon-alpha (IFN-alpha), and insulin-like growth factor-I. Other cytokines detected only in the two IMFH included IL-6, IL-7, IL-8, IFN-gamma, and keratinocyte growth factor. Granulocyte-macrophage-CSF, IL-3, and transforming growth factor-beta staining was present in one of the two IMFH tumors and was not present in the noninflammatory tumors. The immunohistochemical staining was localized to the malignant cells, suggesting deregulated cytokine expression consistent with their monocytic/histocytic origin. Expression of certain cytokines in the IMFH may account for the local inflammatory infiltrate, tumor fibrosis, and the aggressive nature of the malignant cells. We also detected elevated serum levels of SCF, G-CSF, IL-6, and tumor necrosis factor in one or both of the IMFH patients. These latter observations may explain the bone marrow hypercellularity and other paraneoplastic symptoms, including fever, malaise, and weight loss, observed in both patients. Different cytokines present in the two IMFH tumors appear to be responsible for the eosinophilic leukemoid reaction observed in one case and for the granulocytic leukemoid reaction observed in the other patient. They may also be responsible for expansion of the tumor-cell population, fibroblast proliferation, and enhanced secretion of extracellular collagen.
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PMID:Cytokines in inflammatory malignant fibrous histiocytoma presenting with leukemoid reaction. 769 Dec 45

Interleukin-2 (IL-2)-dependent large granular lymphocytes (LGL) with a distinctive surface phenotype were generated from histologically normal duodenal biopsy tissues. Immunoperoxidase staining of the mucosa with an anti-CD56 monoclonal antibody revealed LGL localized in the lamina propria rather than in the epithelium. Light and electron microscopy demonstrated azurophilic and electron-dense cytoplasmic granules. Flow cytometry analysis revealed that these cells express CD45, CD56, CD2, CD7, CD11a, CD18, CD69 and the intermediate affinity (p70) IL-2 receptor (IL-2R) but not CD57, CD16, CD3, CD4, CD5, CD8, CD45RA, CD25, or the high affinity p55 IL-2R. The LGL proliferated when cultured in the presence of human rIL-2 but not in the presence of human rIL-4. Functional studies demonstrated that the LGL had strong cytotoxicity against natural killer (NK) target cells, K562, but not NK-resistant targets such as Colo 205, Melanoma and Epstein-Barr virus (EBV)-transformed B-cell lines. The LGL expressed genes for IL-5, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-alpha) and the corresponding cytokines were detected in culture supernatant. These results provide evidence for an important role of gut mucosal LGL in the induction and regulation of inflammation and immunity in the gut.
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PMID:Morphological, phenotypic and functional characteristics of a pure population of CD56+ CD16- CD3- large granular lymphocytes generated from human duodenal mucosa. 769 28

The aim of this study was to determine whether products of enteric bacteria are able to regulate lymphocyte activation and cytokine production. Whole bacteria and bacterial lysates from different strains of Escherichia coli were tested for their ability to inhibit cytokine production by peripheral blood mononuclear cells as determined by reverse transcription-PCR, Northern (RNA) blotting of cellular RNA, or enzyme-linked immunosorbent assay for cytokine protein. Lysates from two pathogenic strains of E. coli, enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli, inhibited mitogen-stimulated expression of interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon. IL-1 beta, IL-6, IL-8, IL-10, IL-12, and Rantes mRNA expression was not affected. The inhibitory activity was dose dependent, protease and heat sensitive, nondialyzable, and not due to cellular toxicity. The inhibitory activity remained in EPEC strains having mutations in known virulence factors. Nonpathogenic E. coli HB101 transformed with a 22-kb cosmid clone derived from EPEC chromosomal DNA expressed the inhibitory activity. Thus, certain strains of pathogenic E. coli express a protein or proteins encoded by chromosomal genes that selectively inhibit lymphocyte activation and lymphokine production. Therefore, immunosuppressive factors produced by pathogenic bacteria could be important in modifying gastrointestinal immune responses in enteric bacterial infections or gastrointestinal autoimmune diseases.
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PMID:Products of enteropathogenic Escherichia coli inhibit lymphocyte activation and lymphokine production. 776 5

The synthetic antiglucocorticoid RU486 has multiple effects on the immune system. We have recently reported that RU486 suppresses normal lymphocyte proliferation and downregulates interleukin-2 receptors (IL-2R) by decreasing the accumulation of the beta-chain IL-2R mRNA in normal human lymphocytes in culture. To further explore the mechanism of the immunoregulatory actions of RU486, in the present study, we investigated the effects of this molecule on the release of lymphokines from phytohemagglutinin (PHA)-activated normal human peripheral blood lymphocytes (NPBL) in culture. We have found that RU486 differentially regulates the release of lymphokines from PHA-activated NPB lymphocytes. Specifically, RU486 (at concentrations of 1-100 nM) exerts pure antagonist actions by almost completely reversing the inhibitory effects of the glucocorticoid dexamethasone (Dex) on the release of monocyte/macrophages-derived lymphokines, such as IL-1, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha). Dex decreased in a dose-dependent manner the release of the above four lymphokines, with an ID50 of 0.9 +/- 0.1, 4.76 +/- 0.4, 9.8 +/- 1.8, and 1.16 +/- 0.2 nM for IL-1, IL-6, IL-8 and TNF-alpha, respectively. Conversely, RU486 exhibits both agonist and antagonist effects on the release of T-lymphocyte-derived lymphokines. RU486 given alone, exerts agonist/glucocorticoid effects, by decreasing in a dose-dependent manner the release of IL-2 and -3. The maximal inhibitory effect of RU486 was observed at 10 nM and was 64.5 +/- 4.3% of the control value, (n = 6, P < 0.02) for IL-2 and 59.2 +/- 6.3% (n = 6, P < 0.02) for IL-3. The ID50 of RU486 for the release of IL-2 and -3 were 14.6 +/- 2.0 and 11.6 +/- 1.9 nM, respectively, i.e. almost similar with those of Dex. Interestingly, when high doses of RU486 (1 microM) were combined with Dex RU486 exhibited antagonist actions by significantly counteracting the inhibitory effects of Dex on IL-2 and -3 release. In conclusion, the antiglucocorticoid RU486 exhibits complex regulatory actions on lymphokine secretion, dependent upon the type of the lymphokine-producing cell. A pure antagonist effect was observed on the release of monocyte-derived IL-1, IL-6, IL-8 and TNF-alpha. However, when RU486 was given alone it acted as a glucocorticoid agonist on the secretion of T-lymphocyte-derived IL-2 and -3, while combined with the agonist (Dex) it exhibits antagonist effects on the release of the above lymphokines.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vitro differential effects of the antiglucocorticoid RU486 on the release of lymphokines from mitogen-activated normal human lymphocytes. 794 52

The interleukin-2 (IL-2) receptor gamma is an indispensable functional component of IL-2, IL-4, and IL-7 receptors, and thus, is denoted the common gamma chain, gamma c. The present study was undertaken to determine whether human polymorphonuclear neutrophils (PMNs) expressed gamma c chain. Reverse transcription-polymerase chain reaction and Northern blot analysis showed that fresh human PMN constitutively expressed a remarkable level of gamma c mRNA, which is of the size and intensity of that from the peripheral blood mononuclear cells (PBMCs). Granulocyte macrophage-colony stimulating factor, IL-2, and IL-8, which are known to activate PMN functions, failed to regulate the gamma c gene expression. Western blot analysis with a rabbit anti-gamma c polyclonal antibody identified 64-, 58-, and 50-kD gamma c bands in lysates from PMN, but only 64- and 58-kD bands from PBMCs. After the PMNs and PBMCs were treated with tunicamycin to prevent N-linked glycosylation, Western blot analysis detected a single 39-kD band, which is equal to the calculated molecular weight from the cloned cDNA. Thus, our results indicate that PMNs constitutively express high levels of gamma c and the three forms detected are caused by different glycosylation of a protein translated from a single mRNA species.
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PMID:Expression of interleukin-2 receptor gamma chain on human neutrophils. 794 44

Recombinant human interleukin-2 (IL-2) stimulated locomotion and chemotaxis of human blood lymphocytes as measured by shape change to a polar morphology, by orientation in a chemotactic gradient, and by a collagen gel invasion assays. IL-2 stimulated locomotion of a larger number of lymphocytes than IL-8 or macrophage inflammatory protein (MIP)-1 alpha, but the maximally effective concentration of all three was similar (around 100 ng/ml). Activation of the lymphocytes by culture for 24-48 hr in fetal calf serum (FCS), anti-CD3, or purified protein derivative (PPD) increased the proportion of responsive cells, though even direct from blood, > 20% of lymphocytes showed locomotor responses to IL-2, a figure which was similar to the number of IL-2 receptor (IL-2R) beta+ lymphocytes but higher than the number of IL-2R alpha+ cells. The effect of antibodies to IL-2R alpha and IL-2R beta as inhibitors of these responses was therefore tested. Anti-IL-2R beta (alpha IL-2R beta) completely inhibited the response of both resting and activated cells: alpha IL-2R alpha had no inhibitory effect on the locomotion of lymphocytes direct from blood, and only partially inhibited locomotion after culture for 48 hr in alpha CD3 or PPD. The locomotor response to IL-2 was inhibited by pretreatment of the cells with herbimycin, a protein tyrosine kinase (PTK) inhibitor, an observation consistent with PTK control of cytoskeletal activity following binding of IL-2 to IL-2R beta. These results suggest that the beta-chain of the IL-2R is required for activation of lymphocyte locomotion by IL-2 and that binding of IL-2 to this chain alone is sufficient for a response.
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PMID:Chemoattractant activity of IL-2 for human lymphocytes: a requirement for the IL-2 receptor beta-chain. 804 89

The influence of pooled human IgG preparations for intravenous use (i.v.Ig) on in vitro-induced cytokine production was studied at the single-cell level using cytokine-specific monoclonal antibodies (mAb) and indirect immunofluorescent technique. Cultured mononuclear cells from peripheral blood from healthy adult donors were polyclonally stimulated for 96 hr by either direct ligation of T-cell receptors using immobilized anti-CD3 mAb or by a combination of a protein kinase C activator [phorbol 12-myristate 13-acetate (PMA)] and a calcium ionophore (ionomycin) in the absence or presence of i.v.Ig. A marked inhibition of proliferation and blast transformation was noted in all i.v.Ig exposed cultures, despite good cell survival. The production of the T-cell lymphokines interleukin-2 (IL-2), IL-10,interferon-gamma (IFN-gamma) and tumour necrosis factor-beta (TNF-beta) was significantly down-regulated during the whole studied period in the i.v.Ig containing anti-CD3 stimulated cultures. The synthesis of the monokine IL-8 was not suppressed and that of TNF-alpha, which was made by both lymphocytes and monocytes, was only moderately inhibited. Somewhat different and more transient effects were observed in the i.v.Ig-exposed PMA/ionomycin-activated cultures. The production of IL-2, IL-3, IL-4, IL-5, IL-10, TNF-beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) was down-regulated during the initial phase of the cultures up to 48 hr, but not at 48-96 hr. The synthesis of IFN-gamma and TNF-alpha was unaffected of the influence of i.v.Ig during the entire culture period. The expression of IL-2 receptors (IL-2R) was significantly suppressed in the i.v.Ig-treated anti-CD3-activated cells, but not in the PMA/ionomycin-stimulated cultures. Taken together our results indicate that pooled IgG may mediate immunomodulation by direct effects on cytokine production and on T-cell proliferation.
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PMID:Down-regulation of cytokine production and interleukin-2 receptor expression by pooled human IgG. 834

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