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

Gro beta and IL-8 are two pro-inflammatory cytokines with chemotactic activities on neutrophils. Binding studies were performed to ascertain whether their similar biological activities are mediated through the same receptor. Since Gro beta lacks tyrosine residues, recombinant Gro beta containing an additional carboxyterminal tyrosine residue (Gro beta-Tyr) was produced in transfected COS cells, purified to homogeneity and radiolabelled with 125INa. Saturation experiments using [125I]-Gro beta-Tyr allowed us to identify high affinity receptors on human neutrophils (Kd: 2 +/- 0.5 nM and Bmax: 4760 +/- 761 sites/cell). Experiments using [125I]-IL-8 as ligand, showed no significative differences in affinity (Kd: 4 +/- 0.9 nM) but about two times the number of sites (11316 +/- 1810 sites/cell). In competition experiments using [125I]-Gro beta-Tyr, unlabelled IL-8 and Gro beta-Tyr generated superposable displacement curves (IC50: 0.69 +/- 0.15 nM and 0.42 +/- 0.11 nM, respectively). Interesting, IL-8 binding sites could be down-regulated by Gro beta and IL-8, indicating that the two binding sites may be associated. Cross-linking experiments using [125I]-IL-8 revealed two major bands at 70 and 140 kDa, whereas experiments with [125I]-Gro beta-Tyr showed only the 70 kDa band. Taken together, these results suggest that the human neutrophil IL-8/Gro beta receptor is a dimeric complex with two high affinity binding sites for IL-8 and of those two, only one is shared by Gro beta.
Eur Cytokine Netw
PMID:Functional linkage of the Gro beta and IL-8 receptors on the surface of human neutrophils. 821 44

Cytokine treatment in patients with myelodysplastic syndrome (MDS) aims to overcome the maturation defects of myeloid lineage cells associated with cytopenia and cellular dysfunction of mature cells. Since phagocytes play a major role in host defense against microbial infection, we investigated cytokine secretion and oxygen radical release (ORR) from peripheral blood monocytes (PBMC) in a total of 16 MDS patients, 12 patients with refractory anemia (RA) and four patients with RA and excess of blasts (RAEB). Interleukin (IL-6), tumour necrosis factor alpha (TNF alpha), IL-1 beta, and IL-8 secretion from monocytes in response to lipopolysaccharide (LPS) was significantly reduced in the 12 patients with RA compared to 12 healthy controls, whereas no difference was seen in ORR. We further assessed cytokine secretion from monocytes of 10 MDS patients before and after therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or a combination therapy with GM-CSF and cytosine arabinoside (AraC). In all 10 patients, secretion of IL-1 beta, IL-6, and TNF alpha from PBMC increased after cytokine therapy, whereas IL-8 secretion increased only in five patients with GM-CSF or IL-3 therapy receiving a dosage > or = 250 micrograms/m2 per day but decreased in all other patients. ORR increased in all patients on either GM-CSF or IL-3 therapy. These data indicate that the ability of monocytes to secrete secondary cytokines is impaired in MDS patients but can be restored by in vivo administration of GM-CSF and IL-3.
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PMID:Restoration of impaired cytokine secretion from monocytes of patients with myelodysplastic syndromes after in vivo treatment with GM-CSF or IL-3. 823 Dec 42

In this study we have examined the effects of interleukin 10 (IL-10) on polymorphonuclear leukocytes (PMN), and found that it is a potent inhibitor of tumor necrosis factor (TNF), IL-1 beta, and IL-8 secretion triggered by lipopolysaccharide (LPS). Cytokine production by phagocytosing PMN was also inhibited by IL-10, but to a lesser extent than the LPS-induced production. As shown by Northern blot analysis, IL-10 diminished the levels of TNF, IL-1 beta, and IL-8 mRNAs late after the onset of stimulation of PMN with LPS. In addition, we provide evidence that the kinetics of LPS-induced IL-8 production by PMN is composed of two distinct phases. Specifically, our experiments demonstrated that in the first phase, the production of IL-8 is a process directly induced by LPS that lasts for some hours. After this early wave, a second phase begins that is sustained and leads to an elevated production of IL-8 that appears to be due to the endogenous release of TNF and IL-1 beta. This second wave can in fact be blocked by anti-TNF and anti-IL-1 beta neutralizing antibodies, and by IL-10 as the consequence of its downregulatory effects on TNF and IL-1 beta release. Taken together, these findings identify novel biological actions of IL-10 as a suppressor of the inflammatory response.
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PMID:Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. 824 92

Monocyte chemotactic and activating factor (MCAF) is an important mediator of monocyte recruitment to sites of chronic inflammation and neoplasia. In the present study, we determined whether MCAF can also enhance the activation of tumoricidal capacity of monocytes. Human monocytes incubated with MCAF and subthreshold concentrations of lipopolysaccharide (LPS) exhibited synergistic tumoricidal activity against allogeneic A375 melanoma cells, irrespective of their metastatic potential. The sequence of MCAF and LPS treatment was crucial. Monocytes treated first with MCAF for 4 h and then with LPS for 18 h were highly cytotoxic to the melanoma cells, whereas monocytes first treated with LPS and then with MCAF were not. Treatment of monocytes with MCAF and LPS also significantly increased production of tumor necrosis factor. These data suggest that like interferon-gamma, MCAF can prime human monocytes to respond to LPS. Interleukin-8, a chemokine for neutrophils, did not enhance the monocytes' LPS-triggered tumoricidal response. Collectively, these data show that MCAF can influence the recruitment and tumoricidal activation of blood monocytes. Therefore, MCAF may be an important mediator of tumor regression.
Lymphokine Cytokine Res 1993 Oct
PMID:Synergism between human recombinant monocyte chemotactic and activating factor and lipopolysaccharide for activation of antitumor properties in human blood monocytes. 826 May 37

Whole blood and peripheral blood mononuclear cell (PBMC) culture models have been used to study cytokine stimulation and release in vitro. In this study, we characterize the kinetics of the interleukins (IL-1 beta), (IL-6), (IL-8), and tumor necrosis factor-alpha (TNF-alpha) following an endotoxin (ET) challenge using our in vitro whole blood model. Whole blood samples from 10 healthy volunteers were studied. All cytokines were measured by enzyme-linked immunosorbent assay. Peak concentrations of TNF-alpha occurred 2 h after ET challenge followed by a rapid decline in free plasma TNF-alpha concentration (half-life 18.2 min). IL-1 beta was not significantly elevated until 4 h after ET challenge. IL-8 was elevated 1 h after ET challenge. IL-6 concentration exhibited a biphasic peak occurring at 6 and 74 h after ET challenge. We conclude that (1) our whole blood in vitro model produces cytokine release kinetics similar to those reported in vivo, and (2) the presence of either binding proteins or cellular metabolism of TNF-alpha in whole blood produces a similar plasma half-life to that observed in vivo.
Lymphokine Cytokine Res 1993 Apr
PMID:Cytokine kinetics in an in vitro whole blood model following an endotoxin challenge. 832 76

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

The expression and regulation of seven human members of a family of related cytokines, which play a role as effectors of inflammation, were analysed in hemopoietic cells and in fibroblasts. In T lymphocytes all genes: platelet basic protein (PBP); platelet factor 4 (PF-4); IL-8/NAP-1; IP-10; GRO; pAT464 and pAT744 were induced by stimulation with phytohemagglutinin and phorbol 12-myristate 13-acetate (PHA/PMA). In contrast to T cells, only some of the genes were induced upon terminal differentiation of pro-monocytic cells and upon serum stimulation of resting fibroblasts. This distinct expression indicates functional differences of the individual proteins. The expression of inflammatory mediators in fibroblasts suggests the involvement of these cells in inflammatory reactions.
Cytokine 1993 Mar
PMID:Cell type specific expression of members of the IL-8/NAP-1 gene family. 833 26

Lung cytokine production was examined after the intravenous administration of endotoxin to 23 normal human subjects. Bronchoalveolar lavage (BAL) was performed 7 days before and 1.5 or 5 h after endotoxin (4 ng/kg). Cytokine mRNA was evaluated in cell pellets (> 98% macrophages) by use of reverse transcription and the polymerase chain reaction. Immunoreactivity was measured by enzyme-linked immunosorbent assay of 20- to 40-fold concentrated BAL. Interleukin- (IL) 8 was detected in BAL (4-130 pg/ml) but not in the serum at baseline. Few neutrophils were found in BAL (< 1%) despite this IL-8 gradient. Peak serum IL-8 levels occurred 2 h after endotoxin (3,930 +/- 241 pg/ml), but BAL neutrophils and IL-8 did not increase. Peak serum tumor necrosis factor (TNF) levels occurred 1.5 h after endotoxin (1,844 +/- 210 pg/ml), but TNF was detected in only 1 of 20 BAL samples. TNF and IL-8 mRNA were detected by polymerase chain reaction in > 70% of the BAL samples before endotoxin, whereas IL-1 alpha, IL-1 beta, and IL-6 were detected in < 25% of the BAL samples. After endotoxin, no change was detected in cytokine mRNA expression. Actinomycin D treatment of the BAL did not alter the pattern of cytokine mRNA expression. These data suggest that mechanisms exist to insulate the alveolar space from the stimulatory effects of endotoxin and high circulating levels of cytokines. Additional factors appear to control the chemotactic effects of IL-8 on neutrophils in the air spaces during acute systemic inflammation.
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PMID:Compartmentalization of the acute cytokine response in humans after intravenous endotoxin administration. 836 3

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

Per protocol, adults with an Injury Severity Score of 18 or greater underwent Candida antigen titer measurements weekly. If titers were 1:4 or greater, neutrophil function against Candida albicans was determined with use of a tritiated glucose incorporation assay, and polymorphonuclear leukocytes obtained from healthy blood donors were studied concurrently for comparison. Polymorphonuclear leukocytes from healthy blood donors and injured patients with elevated titers were able to inhibit C albicans growth in a dose-dependent fashion. Polymorphonuclear leukocytes from injured patients with elevated titers had a significantly depressed ability to inhibit Calbicans growth compared with those from healthy blood donors at all effector cell-to-target cell ratios tested. Cytokine-treated polymorphonuclear leukocytes from healthy blood donors and injured patients with elevated Candida antigen titers demonstrated significantly improved anticandidal activity at all ratios of polymorphonuclear leukocytes-to-Candida. Granulocyte macrophage-colony stimulating factor was the most potent cytokine at reconstituting polymorphonuclear leukocyte function, followed by interferon gamma and interleukin 8. In conclusion, an elevated Candida antigen titer in injured adults is associated with impaired polymorphonuclear leukocyte antifungal activity. This depressed activity can be reconstituted by the addition of cytokine.
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PMID:Impaired polymorphonuclear leukocyte anticandidal function in injured adults with elevated Candida antigen titers. 841 79


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