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)

Imiquimod (R-837, S-26308) and the analogue S-27609 were evaluated for cytokine induction in human blood cells. Both compounds induced interferon-alpha (IFN), tumor necrosis factor-alpha (TNF), interleukin (IL)-1 beta, and IL-6 with S-27609 being 5 to 10 times more potent. Imiquimod and S-27609 also induced IL-1 alpha, IL-1 receptor antagonist, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and macrophage inflammatory protein-1 alpha. The profile of cytokines induced by imiquimod and S-27609 was different from those seen with lipopolysaccharide and polyinosinic-polycytidylic acid. Kinetic studies with both imiquimod and S-27609 revealed induction of cytokines as early as 1-4 h after stimulation. Although most of the cytokines produced by S-27609 were secreted, significant concentrations of IL-1 alpha and IL-1 beta remained intracellular. Monocytes were largely responsible for the cytokines produced. Finally, S-27609-induced mRNA expression for TNF, IFN, and IL-8, and this induction did not require protein synthesis. Taken together, these studies extend previous findings by showing induction of additional cytokines and providing insight into the mechanism of cytokine induction by these molecules.
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PMID:Cytokine induction by the immunomodulators imiquimod and S-27609. 766 93

We investigated the serum concentrations of a variety of cytokines [granulocyte-macrophage-colony-stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukin (IL) 1 alpha, IL-3, IL-6, IL-8, erythropoietin, tumor necrosis factor alpha, gamma-interferon in 10 patients with advanced ovarian cancer undergoing autologous peripheral blood stem cell (PBSC) harvesting followed by treatment with high-dose cisplatin, etoposide, and carboplatin and PBSC transplantation (chemotherapy was administered on days 1 through 3, PBSCT on day 6). Preliminary observations on cytokine serum levels were performed for 4 patients; on this basis, the kinetics of cytokines was then investigated in greater detail at closely sequential times in 6 further patients. We observed a consistent pattern of sequential GM-CSF, G-CSF, and IL-8 release after chemotherapy/PBSCT in all 10 cases, including the 6 patients monitored in detail: (a) at days 5-10 a GM-CSF peak; (b) at days 12-14 a pronounced release of both G-CSF and IL-8, which always preceded granulocyte recovery by approximately 7 days. At days 17-23, a second GM-CSF peak was monitored in 5 of the 6 patients analyzed in detail, as well as in the other 4 cases. Particularly relevant are the observations that: (a) the peak of G-CSF serum concentration and neutrophil number in the recovery phase are strikingly and directly correlated, thus indicating a key role for G-CSF in granulocyte rescue; (b) the time courses of G-CSF and IL-8 levels are strictly parallel, thereby suggesting a coordinate stimulus for production of granulocytes, mediated by G-CSF, and their activation/migration capacity, mediated by IL-8. Results were essentially negative for IL-3, tumor necrosis factor alpha, and gamma-interferon concentrations (except in one case for each cytokine). An early peak of IL-1 alpha was observed in all 3 analyzed patients, while an IL-6 peak was monitored at days 13-15 in all 4 patients analyzed in detail. The present results indicate a sequential coordinate pattern of cytokine release after ablative therapy and PBSCT and shed light on the mechanisms mediating the recovery of granulocytes, and more generally of hematopoiesis, after stem cell transplantation. Furthermore, these studies may contribute to the design of improved protocols for cytokine administration following myelosuppressive anticancer therapy, as well as to the prediction of granulocytic response.
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PMID:Autologous stem cell transplantation: sequential production of hematopoietic cytokines underlying granulocyte recovery. 768 Feb 83

When administered parenterally, endotoxin stimulates the synthesis of IL-1, TNF-alpha, and IL-6. However, this initial injection induces tolerance; a second injection of endotoxin results in lower levels of circulating cytokines. In our study, five healthy male volunteers between the ages of 18 and 30 were injected with Escherichia coli endotoxin. Four subjects received only saline. Immediately before the injection and 3, 6, and 24 h afterward, PBMC were isolated and stimulated in vitro with endotoxin, IL-1, or toxic shock syndrome toxin-1. Inasmuch as CD14+ monocytes are the primary source of the cytokines induced by these stimuli, results are expressed as cytokine production per 10(6) CD14+ cells. Six h after endotoxin injection, endotoxin-stimulated CD14+ cells synthesized 66% less IL-1 beta (p < 0.01), 47% less TNF-alpha (p < 0.001), 56% less IL-6 (p < 0.01), and 49% less IL-8 (p < 0.01) than cells obtained before the injection. This suppression was not specific for endotoxin; IL-1 beta-induced IL-1 alpha and TNF-alpha were reduced by 84% (p = 0.01) and 68% (p < 0.001), respectively. A decrease in cytokine synthesis was also observed using toxic shock syndrome toxin-1 as a stimulus: 57% for IL-1 beta (p = 0.06), 70% for TNF-alpha (p < 0.01), 56% for IL-6 (p < 0.05), and 71% for IL-8 (p = 0.001). When data were expressed as cytokine production per 10(6) PBMC, cells isolated 3 h after endotoxin injection synthesized significantly less stimulus-induced IL-1, TNF-alpha, IL-6, and IL-8 than did PBMC from saline-injected controls. We conclude that endotoxin tolerance is due, in part, to changes in the stimulus-induced cytokine response of circulating CD14+ cells.
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PMID:Intravenous endotoxin suppresses the cytokine response of peripheral blood mononuclear cells of healthy humans. 768 36

The pleiotropic nature of malignant fibrous histiocytomas (MFH) is manifested as mixed cellular infiltrates consisting of myofibroblasts, histiomonocytes, and neutrophils. We detail in this report the phenotypic characteristics of the human fibrous histiocytoma giant cell tumor (GCT) cell line that establish its mesenchymal origin. The latter is underscored by the ability of GCT cells to express mRNA for transforming growth factor beta (TGF-beta) as well as both A and B chains of platelet-derived growth factor (PDGF). GCT cells also support the binding of CD34+ cells, but less efficiently than do normal marrow stromal cells. Since cytokines elaborated by MFH may mediate in part the recruitment of monocytes and neutrophils into tumor-infiltrated tissues, we have determined the cytokine repertoire of the GCT cell line, already known for its ability to elaborate colony-stimulating factors (CSFs) and interleukin-1 (IL-1). GCT cells express IL-1 alpha, IL-1 beta, IL-6, macrophage colony-stimulating factor (M-CSF or CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and IL-8. No detectable mRNA for IL-3, IL-4, IL-7, and tumor necrosis factor-alpha (TNF-alpha) was detected in GCT cells by polymerase chain reaction (PCR). Expression of cytokine mRNAs was responsive to agents such as dexamethasone (dex), 12-O-tetradecanoyl phorbol 13-acetate (phorbol diester or TPA), and TNF-alpha. Thus, this cell line provides a useful model for understanding the pathobiology of MFH and hematopoietic progenitor interactions with mesenchymal/stromal cells.
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PMID:Phenotypic characterization of the human fibrous histiocytoma giant cell tumor (GCT) cell line and its cytokine repertoire. 768 82

The polymerase chain reaction was used to evaluate cytokine gene expression in bronchoalveolar lavage (BAL) cells and peripheral blood leukocytes in 31 human lung transplant recipients. All patients were maintained on a triple immunosuppression regimen consisting of CsA, AZA, and prednisone. Posttransplant survival ranged from 0.5 to 100.5 months (mean = 16.3 months). Cytokines IL-1 alpha, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, TNF-beta, and IFN-gamma were studied. In BAL, transcripts for IL-1 alpha, IL-7, IL-8, and TNF-beta were found in over 60% of samples and those for IL-5, IL-6, and IFN-gamma in 40-50%, while IL-2 and IL-4 mRNA were rarely found (< 20%). Considerable variation in the frequency of cytokine gene expression between BAL and peripheral blood was observed. When analyzed for the presence of acute pulmonary allograft rejection (without infection), transcripts for IL-4 and IL-6 in BAL demonstrated the greatest increase in frequency compared with nil rejection (P = 0.07 and P = 0.17, respectively). Pulmonary infection (without rejection) was associated with a modest increase in the expression of genes for IL-1 alpha and IFN-gamma (> 10%). Transcripts for IL-4 were not found in association with pulmonary infection, suggesting that this cytokine may be useful as a discriminatory rejection marker.
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PMID:Cytokine gene expression in human lung transplant recipients. 769 39

Cytokine responses are dramatically affected when HIV-1 infected cells are activated with certain antigenic stimuli. We report the effects of HIV-1 tat gene in cytokine modulation, using HIV-1 tat transfected T (Jurkat) and B (Raji) cell lines. Studying the effect of tat and/or PMA + PHA on mRNA expression of 14 cytokines (IL-1 alpha, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-alpha, TNF-beta, GM-CSF, TGF-beta, IFN-gamma and MIP-1 alpha) illustrated differential effects. In addition to the varied effects of tat on the steady state levels of cytokine mRNAs, tat induced the secretion of TNF-beta preferentially in both B and T cell lines, either by itself as in Raji B cell line or synergistically upon PMA + PHA stimulation as in Jurkat T cell line.
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PMID:Differential expression of cytokine genes in HIV-1 tat transfected T and B cell lines. 769 26

Human chorion, but not amnion, tissue explants produced substantial quantities of neutrophil chemoattractant in response to interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF alpha). This suggested that chorion is one of the chemoattractant producing tissues. Therefore, the biochemical properties and the regulation of a chemoattractant in human chorionic cells were examined. IL-1 alpha and TNF alpha stimulated human chorionic cells to produce neutrophil chemotactic factor in both a dose- and time-dependent manner. This chemotactic factor was a heat-stable and trypsin-sensitive protein with an apparent molecular weight of 10000, and it was also immunologically identified as a chemotactic cytokine of the human IL-8 family. Immunohistochemical observations with IL-1 alpha- and TNF alpha-treated chorion explants indicated that trophoblasts and stromal cells, including fibroblast-like and macrophage-like cells, but not endothelial cells, were characterized as IL-8-producing cells. From these observations, it is very likely that both IL-1 and TNF alpha may participate in the production of chemotactic factor/IL-8 in pre-term parturition, accompanied by an intraamniotic infection, along with their known promotive effect on the production of matrix metalloproteinases, which is connected with the destruction of matrix components of fetal membranes.
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PMID:Stimulation of the biosynthesis of interleukin 8 by interleukin 1 and tumor necrosis factor alpha in cultured human chorionic cells. 770 64

We investigated hematopoietic growth factor (HGF) and cytokine gene expression in the bone marrow (BM) and peripheral blood (PB) of healthy individuals as a starting point for delineating the physiologic role of cytokines in steady state hematopoiesis. BM biopsy specimens and PB samples from 7 healthy individuals were analyzed by polymerase chain reaction amplification of reverse-transcribed RNA using gene-specific primer sets. Consistent gene expression in the BM of all 7 individuals was detected for macrophage colony-stimulating factor (CSF), stem cell factor, interleukin-6 (IL-6), IL-7, erythroid-potentiating factor, erythroid-differentiating factor, and insulinlike growth factor 1, all cytokines with reported direct stimulatory effects on in vitro hematopoiesis. Of these, erythroid-potentiating factor and erythroid-differentiating factor appeared to be the only stimulating factors that were also expressed in the PB. Among the cytokines with inhibitory effects on in vitro hematopoiesis IL-4, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, transforming growth factor-beta, and macrophage inflammatory protein-1 alpha were expressed in the BM of the 7 individuals. Except for TNF-alpha, the latter cytokines were also expressed in the PB. Consistent expression in the BM and PB of all tested individuals was also observed for IL-1 beta, IL-1 receptor antagonist, and IL-1 beta converting enzyme, which are all members of the IL-1 family with a possible indirect effect on hematopoiesis. Remarkably, no expression of granulocyte CSF, granulocyte-macrophage CSF, and IL-3 was found in the BM or PB of all investigated individuals (n = 15). This was also the case for IL-1 alpha, IL-2, IL-5, IL-9, IL-12, IL-13, leukemia-inhibiting factor, interferon-gamma, and inhibin. Weak IL-8 and IL-10 expression was found in the BM and/or PB of a minority of investigated individuals. These findings provide insight into which cytokines or HGFs potentially are involved in the autocrine or paracrine regulation of in vivo steady state hematopoiesis. The absence of expression of granulocyte CSF, granulocyte-macrophage CSF, and IL-3 in the BM of healthy individuals implicates that it is highly unlikely that these HGFs are involved in the autocrine or paracrine regulation of constitutive hematopoiesis.
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PMID:Constitutive in vivo cytokine and hematopoietic growth factor gene expression in the bone marrow and peripheral blood of healthy individuals. 771 76

Recent studies suggest that interleukin (IL)-8 exerts a direct influence on several functions such as the chemotaxis or proliferation of human keratinocytes (HK). Since the effects of IL-8 in skin are mediated through specific receptors, we have studied the characteristics of the keratinocyte IL-8 receptor. We could identify specific binding sites for IL-8 in cultured HKs by flow cytometry. Pretreatment of the cells with tumor necrosis factor (TNF)-alpha or IL-1 alpha resulted in a significant increase in IL-8 binding. IL-8 selectively induced expression of HLA-DR antigen, but had no effect on the expression of other cell surface antigens (CD11a, CD18, CD36 and CD54).
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PMID:Interleukin-8 induces HLA-DR expression on cultured human keratinocytes via specific receptors. 771 52

The effect of (R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine (CT-1501R; the nonproprietary name for CT-1501R approved by the United States Name Council is lisofylline), an inhibitor of second messenger signaling through phosphatidic acid, on release of endogenous mediators important in the systemic inflammatory response syndrome (SIRS) was studied using the human whole blood ex vivo assay system. Human blood was stimulated with various endotoxin preparations, zymosan, or protein A, and the levels of secreted monokines were measured by enzyme-linked immunosorbent assay. CT-1501R inhibited tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6 release in a dose-dependent manner and was active with all stimuli tested including Salmonella and Escherichia coli-derived endotoxin, endotoxin from both rough and smooth E. coli strains, as well as zymosan and protein A. CT-1501R inhibited monokine release by approximately 50% at 200 microM and 30% at 50 microM and was independent of the relative potency of stimulus. CT-1501R also inhibited IL-1 alpha or IL-1 beta induction of either TNF-alpha or IL-1 beta and inhibited the synergistic effects of stimulation with both human IL-1 beta and murine TNF-alpha on release of human TNF-alpha. Inhibition of monokine release following stimulation with monokine(s) was, in general, greater than that achieved with lipopolysaccharide (LPS) stimulation. Northern blot analysis showed decreased mRNA accumulation of TNF-alpha and IL-1 beta in CT-1501R-treated samples following LPS stimulation suggesting that CT-1501R acts at least in part, at the pretranslational level. In contrast, CT-1501R does not inhibit LPS-stimulated IL-8 or IL-1 receptor antagonist (IL-1ra) release in human whole blood or IL-1 alpha-induced release of PGE2 in human foreskin fibroblast cells. These data suggest that CT-1501R may be of use for clinical intervention in SIRS.
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PMID:CT-1501R selectively inhibits induced inflammatory monokines in human whole blood ex vivo. 773 59


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