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)

Cytokine-activation pathways in mast cells are supposed to play a significant role in host defense mechanisms and allergic reactions. Interleukin-4 (IL-4) is a well-characterized regulator of growth and function of mast cells. The human mast cell line HMC-1 was established from a patient suffering from mast cell leukemia and was shown to expose IL-4 binding sites. In the present study, the effects of recombinant human (rh) IL-4 and other rh cytokines (IL-2, IL-3, IL-6, IL-8) on expression of cytokine mRNA in HMC-1 cells were examined by Northern blot analysis using oligonucleotide probes. Tumor necrosis factor alpha (TNF-alpha) and IL-1 beta transcripts were found to be expressed constitutively in HMC-1 cells, whereas transcripts for IL-3, IL-4, IL-5, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) could not be detected. Of all cytokines tested, rhIL-4 was found to down-regulate IL-1 beta mRNA expression and formation of immunoreactive IL-1 beta protein in HMC-1 cells. The effect of IL-4 on IL-1 beta gene product expression was time- and dose-dependent (maximum effects obtained with 100 U/mL of rhIL-4). No effect of IL-4 on expression of TNF-alpha mRNA in HMC-1 cells was observed. These results raise the possibility that human mast cells are a source of both TNF-alpha and IL-1 beta. Furthermore, our study provides evidence that IL-4 regulates IL-1 beta gene product expression in HMC-1 cells. The HMC-1 cell line should be a useful tool for studying cytokine activation pathways in human mast cells.
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PMID:Tumor necrosis factor alpha and interleukin-1 beta mRNA expression in HMC-1 cells: differential regulation of gene product expression by recombinant interleukin-4. 833 Jun 51

Selected parameters of cellular immunity relating to cytokine gene activation and responsiveness to interleukin-2 (IL-2) were analyzed in 27 patients with active pulmonary tuberculosis and no human immunodeficiency virus type 1 infection. Cytokine mRNAs were not expressed by peripheral blood mononuclear cells (PBMC) of normal controls. In PBMC of tuberculosis patients, messages for IL-1, IL-8, and tumor necrosis factor-alpha were uniformly expressed, whereas PBMC of only 5 of 18 patients expressed IL-6. PBMC of 7 patients (all of those with systemic symptoms) expressed interferon-gamma mRNA and none expressed IL-2 mRNA. Most patients' cells demonstrated IL-4 mRNA. Limiting dilution analysis of IL-2-responsive cells in PBMC revealed that tuberculosis patients had 10-fold fewer IL-2-responsive cells than did controls.
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PMID:Cytokine gene activation and modified responsiveness to interleukin-2 in the blood of tuberculosis patients. 837 20

The lymphokine profiles were determined in the skin lesions of the three distinct clinical forms of American cutaneous leishmaniasis (ACL), using a reverse transcriptase polymerase chain reaction (RT-PCR) and primers for various lymphokines. The message for interferon-gamma (IFN-gamma), tumour necrosis factor-beta (TNF-beta), and IL-8 was expressed in the three clinical forms of ACL. IL-1 beta mRNA was expressed in most localized (LCL) and mucocutaneous (MCL) leishmaniasis, but in only few of the diffuse cutaneous leishmaniasis (DCL). IL-2 mRNA was detected in about half of the lesions, with more prominent values for MCL. IL-4 mRNA was present in most lesions from the three clinical forms, but markedly increased in DCL. IL-5 and IL-10 mRNAs were expressed in all MCL and in half of the DCL lesions and weakly expressed in LCL lesions. IL-10 mRNA was more abundant in MCL lesions. In contrast, IL-6 and TNF-alpha mRNAs were expressed in a large number of LCL. In MCL, IL-6 mRNA was expressed in most cases and TNF-alpha mRNA in all the cases. In DCL, IL-6 mRNA was absent and TNF-alpha mRNA was weakly expressed. These results suggest that most T cells present in the MCL and DCL lesions secrete a mixture of type 1 and type 2 cytokine patterns, but in DCL granulomas type 2 cytokines predominate. In LCL the cytokine patterns show a mixture of type 1 and type 0 with a preponderance of IFN-gamma over IL-4, and low levels of IL-5 and IL-10. The lack of IL-6 and TNF-alpha mRNAs, and the low expression of IL-1 beta in DCL lesions suggest a defect in the antigen-processing cells that may account for the state of unresponsiveness in these patients.
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PMID:Determination of the cytokine profile in American cutaneous leishmaniasis using the polymerase chain reaction. 844 70

We have examined the effects of mercuric chloride (HgCl2) on growth and IL-4, IL-8, TNF-alpha and MHC class II gene expression in the HMC-1 human leukemic mast cell line. Proliferation, measured by [3H]thymidine incorporation or production of a formazan product (MTT assay), was substantially inhibited by HgCl2 at concentrations of 10(-6) M and above. Inspection of the DNA by agarose gel electrophoresis from HgCl2-treated cells revealed that it was intact, indicating inhibition of DNA synthesis, but not denaturation. HgCl2 inhibited expression of mRNA for IL-8, TNF-alpha and MHC class II at 4 x 10(-6) M and inhibited expression of IL-4 mRNA at 8 x 10(-6) M and above. At a concentration of 10(-5)M, HgCl2 almost completely blocked mRNA expression for IL-4, IL-8, TNF-alpha and MHC class II, but produced negligible inhibition of expression of mRNA encoding the housekeeping gene beta-actin, thus demonstrating selective toxicity for the cytokine and MHC class II genes studied. Pre-exposure of the cells to human recombinant IL-4 prior to treatment with HgCl2 had no effect on expression levels of any of the genes examined. The effects seen in this study are consistent with previous reports showing immunotoxic effects of HgCl2 on other cell types, therefore, the HMC-1 mast cell line may prove useful in further studies of mast cell cytokine gene expression and the mechanisms involved in cytokine gene toxicity.
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PMID:The effects of mercuric chloride on growth, cytokine and MHC class II gene expression in a human leukemic mast cell line. 856 Apr 97

1. The effect of systemic treatment of mice with murine recombinant interleukin-4 (IL-4) or interleukin-10 (IL-10) on neutrophil infiltration into a specific tissue site and nitric oxide (NO) production from peritoneal macrophages was investigated. 2. Intravenously (i.v.) administered IL-4 (0.01-10 micrograms per mouse, approximately 0.3-300 micrograms kg-1, i.v.) and IL-10 (0.01-1 micrograms per mouse, approximately 0.3-30 micrograms kg-1, i.v.) dose-dependently inhibited neutrophil accumulation into a 6-day-old murine air-pouch induced by local application of interleukin-1 beta (IL-1 beta, 5 ng), with approximate ED50s of 0.35 and 0.90 micrograms, respectively. Neither IL-4 (1 micrograms, 30 micrograms kg-1, i.v.) nor IL-10 (1 micrograms, 30 micrograms kg-1, i.v.) prevented leucocyte accumulation in the mouse air-pouches when interleukin-8 (IL-8, 1 micrograms) was used as chemoattractant. Similarly, neither cytokine had any effect on the in vitro up-regulation of CD11b antigen on the surface of murine circulating neutrophils. 3. Treatment of mice with lipopolysaccharide (LPS, 0.3 mg kg-1, i.p.) caused an increase in the formation of NO (measured as nitrite accumulation) in the supernatant of peritoneal macrophages ex vivo. Pretreatment of mice with IL-4 (0.01-1 micrograms i.v., 20 min before LPS), but not with IL-10 (1 micrograms i.v., 20 min before LPS), caused a dose-dependent reduction in this LPS-stimulated formation of nitrite by peritoneal macrophages ex vivo. 4. Activation of murine macrophages with LPS (1 microgram ml-1 for 24 h) in vitro caused a significant increase in nitrite release in the supernatant of these cells. Pretreatment of either J774.2 or peritoneal macrophages with IL-4 (0.1-1 microg ml-1, 20 min before LPS), but not with IL-1O (1 microg ml', 20 min before LPS) caused a concentration-related attenuation of this LPS-stimulated nitrite formation.5 Thus, both IL-4 and IL-10 inhibit the migration of leucocytes (stimulated by IL-1beta>) in vivo; IL-4 (but not IL-10) inhibits the induction of NO synthase caused by LPS in murine macrophages in vitro and ex vivo.
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PMID:Effect of interleukin-4 and interleukin-10 on leucocyte migration and nitric oxide production in the mouse. 856 56

Interleukin-8 (IL-8), a neutrophil-activating cytokine, also activates certain T cell functions such as chemotaxis. We additionally find (n = 6) that recombinant (rIL-8; 1-100 ng/ml), when added to 24 h culture of human CD4+ T cells, suppressed the spontaneous production of IL-4 (50-85%). Steady state production of Il-4 was typically around 30 pg/ml, determined by use of a solid- phase immunoabsorbant assay. De novo synthesis of IL-4 from CD4+ T cells cultured for 3 days was also evaluated by use of detection of [35S]methionine incorporation, as visualized by autoradiography of 2-D gels, and showed that IL-8 suppressed IL-4 production. This suppression of IL-4 production was confirmed in the cytosol fraction by use of Western blotting. The effect of IL-8 (100 ng/ml) was comparable to that of 10 ng/ml recombinant interferon-gamma, both strongly suppressing IL-4 production. The regulatory effect of IL-8 on IL-4 production was also indicated by the fact that addition of a neutralizing monoclonal anti-IL-8 antibody (WS.4) enhanced the spontaneous IL-4 production when added to the culture of CD4+ T cells, thereby probably inactivating the effect of IL-8 originating from the cultured T cells. Also, we observed that IL-4 mRNA expression was down-regulated when the CD4+ T cells were cultured for 12 h in the presence of 100 ng/ml IL-8. The suppression of IL-4 mRNA expression could be prevented by adding anti-IL-8 (20 microgram/ml) or IL-10 (100 ng/ml) l h before adding rIL-8. Thus, IL-8 may be an important regulator of CD4+ T cell-derived IL-4, thereby possibly regulating the balance between humoral and cellular T cell-dependent responses.
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PMID:IL-8 induces T cell chemotaxis, suppresses IL-4, and up-regulates IL-8 production by CD4+ T cells. 860 20

Janus kinase-3 (Jak3) is a nonreceptor tyrosine kinase functionally coupled to cytokine receptors which share a "common" gamma chain (gamma c). Mutations in gamma c and Jak3 genes have been identified in X-linked and autosomal severe combined immuno deficiency (SCID), respectively. Jak3 is expressed and activated in myelomonocytic cells. The present study was designed to define the structural alteration responsible for lack of Jak3 in a patient with autosomal SCID and to characterize monocyte function in the absence of this signal transduction element, as well as to establish the whole exon-intron structure. Polymerase chain reaction analysis, performed with primers designed on exon sequences, identified 20 exons spanning approximately 15 kb. These primers, or others designed on the flanking sequences provided in the present report, can be used to amplify the whole gene, allowing the definition of the molecular defects in all cases, including prenatal diagnosis, in which transcript analysis is not possible. On this basis, the deletion transcript found at the homozygous state in patient CM, with both his consanguineous parents being heterozygous for the deletion, was associated with mutation (T to C) of a splice donor site of intron 16 that was also detected in his mother's DNA. Monocytes from Jak3-SCID showed normal cytokine production in response to interleukin-4 (IL-4) (release of IL-1 receptor antagonist) and IL-2 (release of tumor necrosis factor-alpha and IL-8). Lipopolysaccharide-induced cytokine production was also normal and was blocked by IL-4 in Jak3- SCID monocytes. Interferon-gamma induced augmented expression of major histocompatibility class II in Jak3-SCID monocytes. These data indicate that Jak3, expressed and activated in myelomonocytic cells, is dispensable for monocyte differentiation and responsiveness to cytokines that interact with gamma c receptors as well as to other regulatory signals.
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PMID:Monocyte function in a severe combined immunodeficient patient with a donor splice site mutation in the Jak3 gene. 870 36

Intrathyroidal lymphocytes are a source of cytokines thought to stimulate or maintain the immune process within the thyroid in Graves' disease (GD) and Hashimoto's thyroiditis (HT). Quantitative assessment of the cytokine profile may provide important clues as to the Th1/Th2 balance prevailing in these diseases. We analyzed cytokine mRNA expression levels in thyroid tissue samples from 13 patients with GD, 2 with HT, 5 with nontoxic multinodular goiter (NTG), and 4 with thyroid autonomy (nodular = TAnod and perinodular = TAperi tissue) using multispecific competitor fragments with primer sequences for IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-gamma, CD25, and CD3 delta-chain mRNA. Patients with GD were subdivided into two groups according to their serum levels of antibodies to thyroperoxidase (anti-TPO; GDhigh > 4000 U/mL, GDlow < or = 200 U/mL). These levels correlated positively with the CD3 delta-chain mRNA levels (r = 0.83) and with the T cell infiltration (r = 0.71) as determined by immunohistochemistry. Patients with GDhigh demonstrated 2- to 4-fold higher IL-4 mRNA levels (as compared to all other investigated groups) and significantly higher IL-10 mRNA levels as compared to HT, GDlow, and TAnod patients. Patients with GDhigh also had significantly higher levels of IFN-gamma, IL-1 beta, IL-8, and CD25 mRNA as compared to GDlow. The highest IFN-gamma, IL-2, and CD25 mRNA levels were found in HT. The lowest mRNA levels of all the investigated groups were detected in TAnod. No significant differences in IL-6 and IL-8 mRNA levels were found between most of the patient groups. In summary, patients with GDhigh showed a shift to a more Th2-driven cytokine pattern. In contrast, the increase mRNA levels of Th1-related cytokines found in HT indicate predominantly T cell-mediated cytotoxic processes.
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PMID:Different cytokine mRNA profiles in Graves' disease, Hashimoto's thyroiditis, and nonautoimmune thyroid disorders determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). 873 79

Because dendritic cells (DC) are the most potent antigen-presenting cells involved in many pathophysiological responses, we investigated the effect of chemokines on the migration of these cells in an effort to determine whether chemokines may contribute to the initiation of immune responses. CD34+ progenitor cells isolated from umbilical cord blood were grown in suspension cultures with cytokines and expanded 50- to 100-fold. A variable proportion of the cells expressed markers consistent with DC. The proportion of CD1a+ DC was increased when the cells were cultured with interleukin-4 (IL-4). These cells expressed specific binding sites for C-C and C-X-C chemokines. Cells cultured with or without IL-4 had similar binding profiles. All C-C chemokines tested, including monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein-1 alpha (MIP1 alpha), MIP-1 beta, and RANTES, induced migration of DC-enriched cells cultured with or without IL-4 with MCP-3 being the most potent chemoattractant. Phenotypic analysis of cell migrating in response to C-C chemokines showed that CD1a+ cells were indeed attracted across the polycarbonate filters, and there was no preferential attraction of contaminating CD14+ monocytes by C-C chemokines. DC-enriched cells also expressed specific binding sites for IL-8 and NAP2, which failed to induce cell migration. Our results suggest that C-C chemokines may participate in the recruitment of DC to amplify host defense.
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PMID:Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro. 883 Jul 93

Preterm labor associated with intrauterine infection is characterized by increased amniotic fluid concentrations of various proinflammatory cytokines, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage inflammatory protein-1alpha (MIP-1alpha). The purpose of this study was to determine if preterm labor in women with clinically evident chorioamnionitis is marked by elevations of the anti-inflammatory cytokine interleukin-4 (IL-4) and the T cell growth factor IL-2. Amniotic fluid samples were obtained from (1) women at term, not in labor (n = 10); (2) women at term, in labor (n = 10); (3) women with preterm contractions but undelivered within 1 week of amniotic fluid collection (n = 10); (4) women with preterm labor and delivery without clinically evident chorioamnionitis (n = 10); (5) women with preterm labor associated with chorioamnionitis (n = 8); and (6) women with preterm labor and delivery without infection matched with patients with chorioamnionitis (n = 8). Amniotic fluid concentrations of IL-4 and IL-2 were determined for each sample with a specific and sensitive enzyme-linked immunoassay. We found that women with infection-associated preterm labor and delivery had significantly higher concentrations of IL-4 when compared to appropriately matched controls (p < 0.05). Additionally, women with preterm labor and delivery not associated with infection had higher amniotic fluid IL-4 concentrations than women with preterm contractions but no labor (p < 0.05). Women with term labor had rare modest elevations of amniotic fluid IL-4. No IL-2 was detected in any sample. Our data indicate that amniotic fluid IL-4 is elevated in women with preterm labor and delivery, particularly in association with chorioamnionitis. We suggest that IL-4, although previously considered an anti-inflammatory agent, may have a paradoxical proinflammatory role in the pathogenesis of infection-associated preterm labor.
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PMID:Elevation of amniotic fluid interleukin-4 concentrations in women with preterm labor and chorioamnionitis. 896 Jun 15

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