Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In vitro, IL-10 inhibits T cell proliferation and LPS-induced monocyte production of IL-1, TNF-alpha, IL-6, and IL-8. We studied the safety and immunomodulatory effects of IL-10 administration in humans. Seventeen healthy volunteers received a single i.v. bolus injection of either human IL-10 (1, 10, or 25 micrograms/kg) or placebo. Routine safety parameters, lymphocyte phenotypes, T cell proliferative responses, and stimulus-induced cytokine production were assessed before and 3, 6, 24, and 48 h after injection. There were no adverse symptoms or signs after IL-10 administration. A transient neutrophilia and monocytosis that peaked at 6 h (45-160% above base line) was observed. However, lymphocyte counts fell by 25% 3 and 6 h after the injection (p < 0.01). In particular, lymphocytes expressing the T cell surface markers CD2, CD3, CD4, CD7, and CD8 were significantly decreased. Mitogen-induced T cell proliferation was suppressed by up to 50% (p < 0.01) in the two higher dose groups. Significant dose-dependent inhibition (65-95%) of TNF-alpha and IL-1 beta production from whole blood stimulated ex vivo with endotoxin occurred after each dose of IL-10. In contrast, there was no reduction in the production of their respective antagonists, TNF soluble receptor p55 or IL-1 receptor antagonist. We conclude that a single intravenous injection of IL-10 is safe in humans, has inhibitory effects on T cells, and suppresses production of the pro-inflammatory cytokines TNF-alpha and IL-1 beta.
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PMID:A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. 773 Jun 51

The eradication of minimal residual blast populations by activation of autologous cytotoxic cells with interleukin 2 (IL-2) is a new promising tool in the treatment of acute myelocytic leukemia (AML). However, the immunological effector cells are not yet clearly defined. The present study was designed to investigate the presence of cytotoxic precursor cells in active AML and to identify phenotypical and functional characteristics of autologous anti-leukemic cytotoxic effector cells. For this purpose, mononuclear cells (MNC) containing at least 70% leukemic blasts were isolated from bone marrow of untreated AML and cultured in the presence of 3000 IU/ml recombinant IL-2 (rIL-2) for 6-8 weeks. Under these conditions, T-cells were selected in the bone marrow cultures and overgrew the leukemic blasts. The resulting T-cell populations were cloned by limiting dilution and the clones obtained were characterized for their phenotypical and functional patterns. Totally, cloning resulted in 68 clones and a few cell lines. The clonality was verified by RT PCR analysis of TCR V beta gene expression. All clones obtained stained positive for CD2, CD3, DR and CD56. The vast majority (68%) of T-cell clones/lines was CD4+, a few clones expressed CD8 (19%) or CD4 and CD8, and four clones were of TCR gamma delta origin. Seven of 15 clones tested, including three CD4+, two CD8+ and two TCR gamma delta(+)-clones were found to be cytotoxic against autologous leukemic blast cells. All except one clone expressed oncolytic activities against allogeneic blasts too. One of the TCR gamma delta(+)-clones demonstrated NK activity by lysis of K562 targets. The majority of the T-cell-clones released IL-2, IL-8, TNF-alpha, GM-CSF but only a few IFN gamma and expressed high levels of mRNA for IL-2, TGF-beta and IL-10. None of the clones was found to produce IL-3, IL-4, IL-7 and TNF-beta. The data provide evidence of the existence of T-cell precursors in untreated AML bone marrow differentiating to cytotoxic cells with activity against autologous and allogeneic AML blast cells.
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PMID:Bone marrow-derived T-cell clones obtained from untreated acute myelocytic leukemia exhibit blast directed autologous cytotoxicity. 786 44

To date no hematopoietic progenitors of dendritic Langerhans' cells (DLC), which represent an highly efficient class of antigen presenting cells, have been identified or the cytokines they elaborate have been defined. Here we describe an acute leukemia patient whose blasts (90-96% in peripheral blood and bone marrow) had a phenotype consistent with putative progenitors of DLC. The patient was treated with ara-C and VP-16 but did not achieve remission. The blasts had lobulated nuclei, no cytoplasmic vacuolation or Auer rods and were weakly positive for acid phosphatase and non-specific esterase and negative for PAS, granzyme A, dipeptidyl aminopeptidase IV, ATPase/ADPase and lysozyme production. The blasts were positive for CD1a, CD4, CD16, CD35, HLADR, HLADQ, CD11b, CD11c, CD14, CD33, CD34, CD11a, CD71, CD19, CD25, IL-2R beta and negative for CD2, CD7, CD8, CD10, CD22, CD56, CD57, surface or cytoplasmic CD3, TCR delta and TCR beta, HTLV-1p19 and P-glycoprotein. On liquid culture with or without 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days, the blasts formed aggregates of proliferating and elongating cells on the wall of the flasks with a decline in CD34, numerous dendritic processes appeared on the cells and there was strong positivity for ATPase/ADPase, but no other changes in phenotype. No macrophages were observed, indicating derivation from separate DLCs. Cytogenetic analysis showed chromosomal abnormalities and electron microscopy showed Birbeck granules. Southern blotting of DNA showed rearrangement of one allele for both JH and TCR beta but no HTLV-1 related sequences. Culture supernatants from blasts cultured with or without TPA showed the production of large amounts of IL-8, IL-6, TNF-alpha, MIP-1 alpha, IL-10 and interferon gamma and modest amounts of IL-1 alpha, GM-CSF and stem cell factor. The presence not only of CD1a, HLADR, HLADQ and many other characteristics including Birbeck granules, but also differentiation along the lines of DLC with appearance of dendritic processes on the cells and expression of ATPase/ADPase activity, indicate that the leukemic blasts in our patient represented a leukemic counterpart of normal progenitors of DLC and the leukemia a new entity which could possibly be classified as AML-M8. Lastly, many pro-inflammatory cytokines produced by DLC could contribute to inflammation and IL-10 to immunosuppression.
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PMID:Phenotype, genotype and cytokine production in acute leukemia involving progenitors of dendritic Langerhans' cells. 791 55

The cell line AG-F was isolated from the marrow of a neuroblastoma patient undergoing myeloablative treatment and autologous bone marrow rescue. A year later, the patient developed a Hodgkin's type lymphoma. AG-F cell line demonstrated an unusual phenotype, lacking surface CD2 and CD3, but expressing high levels of CD4, CD5, CD7, CD29, and CD45RO. Markers associated with Hodgkin's lymphoma cells, CD15 and CD30, were also positive. AG-F cells grow in suspension in clusters of 50-200 cells, with a doubling time of 9 h. They can also grow in serum-free medium and form tumors in nude mice. AG-F cells have amplified N-myc and c-myc and high levels of the corresponding mRNA transcripts. Cytogenetic analysis revealed a DNA index by flow cytometry of near tetraploid cells and a karyotype of 85-87 chromosomes, with consistent abnormalities in chromosomes 1, 5, and 9. Gene rearrangement studies revealed rearrangement of the beta gene of the T-cell receptor. AG-F cells secrete high levels of IL-6, IL-8, IL-10, and GM-CSF. Cell adherence and formation of long processes could be induced by fibronectin and were enhanced by exposure to PMA. Cells exposed to phorbol myristate acetate (PMA) had increased expression of CD11a, CD11b, CD18, CD45RO, and HLA-DR, whereas expression of CD15 and CD30 was markedly decreased. Similarly, the level of c-myc and N-myc oncoproteins and the levels of the cytoskeletal proteins, actin, tubulin, and vimentin markedly decreased early after PMA-induced differentiation.
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PMID:Isolation and characterization of an early T-helper/inducer cell line with a unique pattern of surface phenotype, constitutive cytokine secretion and myc oncogene expression. 825 4

Chemokines, which include interleukin (IL)-8, are a family of pro-inflammatory molecules with potent chemoattractant activity on neutrophils, as well as other cell types. IL-8 can be recovered from many inflammatory sites. To test the hypothesis that Th2-type allergen-specific T cells, known to be the main cell type governing the allergic inflammation, are a source of IL-8 and to investigate whether IL-8 release is influenced by the nature of the in vitro mitogenic or co-mitogenic stimulation, cypress-specific T-cell clones (TCC) were generated from five allergic subjects during in vitro seasonal exposure to the allergen. Purified cypress extract was produced directly from freshly collected pollen and used for in vitro stimulation of PBMC bulk cultures. After 5 days priming and a further 7 day period of IL-2-driven cell expansion, monoclonal antibodies to CD3, CD2 and CD28 were adopted for in vitro restimulation of allergen-specific cell lines or, subsequently, secondary established TCC. The induction of apoptosis was detected by propidium iodide (PI) cytofluorimetric assay. Basal and co-stimulation-induced IL-8 production was measured by an ELISA method. Both cypress-specific T-cell lines and TCC secreted appreciable amounts of IL-8. By cross-linking T-cell lines or Th2 CD4+ TCC with CD3, CD2 or CD28 MoAbs, the authors observed a great stimulation-induced IL-8 secretion, preferentially after CD2 or combined CD2/CD28 stimulation. In addition, CD4+ clones released large amounts of IL-8 into culture supernatants after CD2 stimulation while undergoing programmed cell death (30-40% hypodiploid DNA profile of PI-stained cells). In contrast, CD3 crosslinking was unable to determine the release of IL-8 or the induction of apoptosis. Taken together, these results suggest that incomplete TcR engagement by allergen may lead to the secretion of pro-inflammatory cytokines with a contemporary induction of apoptosis in a significant number of target cells. This phenomenon may represent an additional way for local recruitment of neutrophils and basophils.
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PMID:Co-stimulation-induced release of pro-inflammatory cytokine interleukin-8 by allergen-specific T cells. 869 95

We conducted a double-blind, placebo-controlled study to investigate the safety, pharmacokinetics, and immunological properties of interleukin-10 (IL-10) administration in healthy humans. Volunteers received a single intravenous bolus injection of recombinant human IL-10 (1, 10, or 25 micrograms/kg) or placebo. Cytokine production in whole blood and peripheral blood mononuclear cells (PBMC) was assessed before and 3, 6, 24, and 48 hr after the injection. Peak serum concentrations of IL-10 (15 +/- 1.1, 208 +/- 20.1, and 505 +/- 22.3 ng/ml) occurred after 2-5 min for 1, 10, and 25 micrograms/kg IL-10, respectively. The terminal-phase half-life was 3.18 hr. A transient leukocytosis (24-63% above baseline) was observed 6 hr after injection, which coincided with a dose-dependent decrease (12-24%) in neutrophil superoxide generation. There was a marked inhibition (60-95%) of endotoxin-induced IL-6 production from whole blood in each group receiving IL-10. Production of IL-8 in endotoxin-stimulated blood was reduced in the 10 micrograms/kg group. In PBMC stimulated with phytohemagglutinin and phorbol ester, there was a decrease (72-87%) in interferon-gamma (IFN gamma) production 6 hr after IL-10 with a return to pre-IL-10 levels after 24 hr. This reduction was only partially associated with a decrease in the number of CD2-bearing cells. We conclude that IL-10 administration into humans is without significant side effects, and a single injection reduces ex vivo production of IL-6, IL-8, and IFN gamma.
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PMID:Clinical, hematologic, and immunologic effects of interleukin-10 in humans. 888 99

The effect of inflammatory mediators on the expression of several surface adhesion molecules on the human mast-cell line (HMC)-1 was studied. By flow cytometry, it could be shown that among several surface adhesion molecules (ICAM-1/CD54, VLA-4/CD49d, Mac-1/CD11b, LFA-1/CD11a, LFA-2/CD2, LFA-3/CD58, VCAM-1), only the constitutively expressed immunoglobulin family member intercellular adhesion molecule-1 (ICAM-1) is modulated by proinflammatory cytokines on HMC-1 mast cells. Stimulation with tumor necrosis factor-a (TNF-alpha) and interferon-gamma (IFN-gamma) resulted, in addition to interleukin-(IL-)4, in selective upregulation of ICAM-1 expression. Costimulation of either IL-4 or IFN-gamma with TNF-alpha further increased the ICAM-1 expression as compared to the stimuli alone. In contrast, stem-cell factor (SCF), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-10, IL-8, monocyte chemotactic and activating factor (MCAF), and the complement split product C5a failed to modulate the expression of any adhesion molecule examined. The levels of cytoplasmic free calcium in HMC-1 mast cells were not altered by cross-linking surface ICAM-1, suggesting linkage of other intracellular signaling pathways. This cytokine-induced upregulation of ICAM-1 expression might reveal a putative regulatory mechanism of mast-cell interaction with effector cells bearing the counterparts of ICAM-1 (CD54), the molecules Mac-1 (CD11b/CD18) and leukosialin (CD43), and the principal ligand LFA-1 (CD11a/CD18).
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PMID:Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on the human mast-cell line (HMC)-1 by inflammatory mediators. 890 94

Dendritic cells (DC) represent the most powerful professional antigen-presenting cells (APC) in the immune system. The aim of the present study was to analyse, on a single-cell basis by multiparametric flow cytometry with simultaneous four-colour staining and a two-step acquisition procedure, the immunophenotypic profile and cytokine production of DC from 67 normal whole peripheral blood (PB) samples. Two clearly different subsets of HLA-II+/lineage- were identified on the basis of their distinct phenotypic characteristics: one DC subset was CD33strong+ and CD123dim+ (0.16 +/- 0.06% of the PB nucleated cells and 55.9 +/- 11. 9% of all PB DC) and the other, CD33dim+ and CD123strong+ (0.12 +/- 0.04% of PB nucleated cells and 44.53 +/- 11.5% of all PB DC). Moreover, the former DC subpopulation clearly showed higher expression of the CD13 myeloid-associated antigen, the CD29 and CD58 adhesion molecules, the CD2, CD5 and CD86 costimulatory molecules, the CD32 IgG receptor and the CD11c complement receptor. In addition, these cells showed stronger HLA-DR and HLA-DQ expression and a higher reactivity for the IL-6 receptor alpha-chain (CD126) and for CD38. In contrast, the CD123strong+/CD33dim+ DC showed a stronger reactivity for the CD4 and CD45RA molecules, whereas they did not express the CD58, CD5, CD11c and CD13 antigens. Regarding cytokine production, our results show that while the CD33strong+/CD123dim+ DC are able to produce significant amounts of inflammatory cytokines, such as IL-1beta (97 +/- 5% of positive cells), IL-6 (96 +/- 1.1% of positive cells), IL-12 (81.5 +/- 15.5% of positive cells) and tumour necrosis factor-alpha (TNF-alpha) (84 +/- 22.1% of positive cells) as well as chemokines such as IL-8 (99 +/- 1% of positive cells), the functional ability of the CD123strong+/CD33dim+ DC subset to produce cytokines under the same conditions was almost null. Our results therefore clearly show the presence of two distinct subsets of DC in normal human PB, which differ not only in their immunophenotype but also in their functionality, as regards cytokine production.
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PMID:Extensive characterization of the immunophenotype and pattern of cytokine production by distinct subpopulations of normal human peripheral blood MHC II+/lineage- cells. 1059 57

Human dermal fibroblasts (HDF) undergo activation and secrete cytokines when cocultured with T cells. Here, we identify potent activators of HDF among human peripheral CD2(+)-lymphocytes. Populations with strong HDF activating capacity consisted essentially of cells with a natural killer (NK) surface marker phenotype (CD3(-), CD4(-), CD8(-), CD56(+)). Addition of these cells to HDF resulted in rapid increase of intracellular free calcium concentrations as an early rapid cell activation signal. Upregulation of mRNA encoding for the inflammatory cytokines IL-1 beta and IL-6 as well as for chemokines IL-8 and MCP-1 was detected after cells were cocultured. Elevated concentrations of IL-6 and IL-8 were found in coculture supernatants of HDF and NK-cells. Skin-homing NK cells leaving the blood-stream during an inflammatory skin reaction might therefore represent potent activators of local inflammatory cytokine and chemokine production.
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PMID:Natural killer cells activate human dermal fibroblasts. 1109 44


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