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)

We investigated the response of purified and cloned human thymic epithelial cells (TEC) to IL-1, IL-4, and IFN-gamma stimulation in vitro. IL-1 alpha strongly up-regulated the production of granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), IL-6, and IL-8, as measured by specific immunoenzymetric assays and by increased steady state mRNA levels. IL-4 or IFN-gamma did not induce these cytokines in TEC but in a sustained and dose-dependent manner down-regulated the IL-1-induced GM-CSF protein and mRNA levels. Only IFN-gamma, and not IL-4, suppressed the IL-1-induced G-CSF and IL-8 production, as shown at both the protein and mRNA levels. The inhibition was dose dependent, sustained for at least 96 h, and more pronounced for G-CSF than for IL-8. In contrast, both IL-4 and IFN-gamma enhanced the IL-1-induced IL-6 production. IL-4 and IFN-gamma had additive effects to increase IL-6 secretion and to more completely suppress the IL-1-induced GM-CSF. Analyses of cell surface molecules showed that intercellular adhesion molecule 1 (ICAM-1) expression on TEC was increased by IL-1 or IFN-gamma. IL-4 slightly down-regulated constitutive ICAM-1 levels but did not significantly modify the levels of expression induced by either IL-1 or IFN-gamma. MHC class II expression was induced by IFN-gamma but not by IL-1 or IL-4. The combination of IL-1 and IL-4 with IFN-gamma did not alter the levels of class II MHC Ag induced by IFN-gamma. In conclusion, TEC cytokine production and cell surface molecule expression are differentially regulated via a complex cytokine network. Our data suggest that developing T cells provide, in part, the signals controlling the function of their supporting stroma.
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PMID:IL-1, IL-4, and IFN-gamma differentially regulate cytokine production and cell surface molecule expression in cultured human thymic epithelial cells. 171 90

Interleukin-8 (IL-8) stimulated an increase in cytoplasmic-free Ca2+ ([Ca2+]i) and intracellular pH (pHi) in parallel at low concentrations (0.5 to 5 ng/mL), and stimulated O2- release and membrane depolarization in parallel at high concentrations (50 to 5,000 ng/mL). IL-8-induced O2- release was potentiated by tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte-CSF (G-CSF) in a dose-dependent manner, whereas it was inhibited by cyclic AMP agonists. These characteristics and the time-courses of the responses stimulated by IL-8 were similar to those stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP), except that the cells stimulated by IL-8 showed shorter duration and less magnitude in some responses. In addition, IL-8 was found to be a potent priming agent and to enhance O2- release stimulated by FMLP. The priming effect of IL-8 was very rapid and was maximal within 5 minutes of preincubation. The dose-response curves for priming were identical to those for triggering of an increase in [Ca2+]i and pHi. The potency of the maximal priming effects on FMLP-induced O2- release was TNF greater than GM-CSF greater than IL-8 greater than G-CSF. The combination of IL-8 and the suboptimal concentrations of TNF or GM-CSF resulted in the additive priming effect, whereas the combination of the optimal concentration of IL-8 and the optimal concentration of TNF, GM-CSF, or G-CSF resulted in the effect of more potent priming agent alone. These findings suggest that IL-8 stimulates or primes human neutrophils according to its concentrations and cross-talks with TNF, GM-CSF, G-CSF, or FMLP at the inflammatory sites.
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PMID:Stimulation and priming of human neutrophils by interleukin-8: cooperation with tumor necrosis factor and colony-stimulating factors. 172 9

There is increasing evidence that epidermal cytokines may have an important role in mediating inflammatory and immune responses in the skin. A number of cell types in the epidermis are capable of secreting cytokines including keratinocytes, Langerhans cells, melanocytic cells, and even Merkle cells. Keratinocytes are the major source of cytokines in the epidermis and have been reported to secrete IL-1, IL-3, IL-6, IL-8, CSF, TNF alpha, TGF alpha, TGF beta, and PDGF. Normally these cytokines are not actively secreted by keratinocytes; however, a number of agents are capable of mediating keratinocyte cytokine production, including cytokines themselves. We examined the effect of a number of cytokines on keratinocyte IL-1, IL-6, GM-CSF, and PDGF production. It was found that these keratinocyte cytokines are all modulated by one or more cytokines, including several that keratinocytes themselves secrete. These effects appear to be mediated by high-affinity cytokine receptors on keratinocytes. We are only beginning to understand the molecular mechanisms underlying the production, regulation, and precise role of keratinocyte cytokines in normal and diseased skin; however, recent studies suggest that cytokines secreted by epidermal cells and lymphoid cells may be important modulators of keratinocyte cytokine production.
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PMID:Cytokine modulation of keratinocyte cytokines. 216 84

A neutrophil-activating peptide (NAP)/IL-8 produced by LPS-stimulated human peripheral blood monocytes was biochemically purified and functionally characterized by different investigators. Work conducted in our laboratory showed that NAP/IL-8 as well as variants of this peptide are produced by a variety of cells (e.g., monocytes, T lymphocytes, endothelial cells) and that lesional psoriatic scales contain large amounts of biologically active NAP/IL-8. We now investigated human dermal fibroblasts for production of NAP/IL-8. The peptide was detected by immunocytochemistry by using the mAb 46E5. NAP/IL-8 mRNA was visualized by high resolutive fluorescent in situ hybridization with biotinylated antisense/sense RNA probes. Among the various stimuli used [human (h)rIL-1 alpha, hrTNF-alpha, hrIL-3, hr-granulocyte-macrophage-CSF, LPS, FMLP, and platelet-activating factor (PAF)] only hrIL-1 alpha (100 U/ml) and hrTNF-alpha (100 ng/ml) induced the transcription and translation of NAP/IL-8. In contrast to monocytes, LPS was without effect in cultured human dermal fibroblasts. Both NAP/IL-8 and NAP/IL-8 mRNA were found in the cytoplasm adjacent to the nucleus, but interestingly NAP/IL-8 mRNA was not restricted to the cytoplasm. In positive cells only two small bright spots were randomly distributed in the nucleus. Most likely these spots represent transcription sites where NAP/IL-8 mRNA is accumulated during gene expression. Our observations show that stimulation of dermal fibroblasts with the cytokines hrIL-1 alpha and hrTNF-alpha results in expression of IL-8.
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PMID:Detection of neutrophil-activating peptide NAP/IL-8 and NAP/IL-8 mRNA in human recombinant IL-1 alpha- and human recombinant tumor necrosis factor-alpha-stimulated human dermal fibroblasts. An immunocytochemical and fluorescent in situ hybridization study. 240 62

The infiltration of polymorphonuclear neutrophils (PMN) into the upper dermis which characterizes the skin lesions of dermatitis herpetiformis (DH) has never been satisfactorily explained. This study has shown that lesional skin of patients with DH has increased expression of endothelial leucocyte adhesion molecules (ELAM) in the deep dermis, combined with a markedly increased staining for interleukin 8 (IL-8) in the basal epidermal layer. Dendritic cells which stained for granulocyte macrophage colony stimulating factor (GM-CSF) were also observed at the dermo-epidermal junction, and this phenomenon was more pronounced in lesional than in uninvolved DH skin. ELAM, IL-8 and GM-CSF are known to promote infiltration and activation of PMN, and it is suggested that these cytokines may play a key role in the generation of DH lesions.
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PMID:The role of cytokines in the generation of skin lesions in dermatitis herpetiformis. 750 4

Previously, we have shown that Escherichia coli alpha-hemolysin represents a potent stimulus for inflammatory mediator release (O2- release, beta-glucuronidase release, and leukotriene generation) from human polymorphonuclear granulocytes (PMN) as well as for histamine release from a human lymphocyte-monocyte-basophil cell suspension (LMB). In contrast, the E. coli alpha-hemolysin leads to a downregulation of cytokine release (interleukin 6 [IL-6], tumor necrosis factor alpha, and IL-1 beta) from human LMB. This study was undertaken (i) to analyze the priming efficacy of growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF] and granulocyte CSF [G-CSF]) on inflammatory mediator release from human PMN and LMB challenged with hemolysin-producing E. coli bacteria as well as with cell-free E. coli alpha-hemolysin and (ii) to identify major components involved in GM-CSF and G-CSF priming. GM-CSF pretreatment led to an increased chemiluminescence response from human PMN by up to 100%, leukotriene B4 generation was enhanced up to fivefold, and histamine release from human LMB increased from 45% +/- 15% to 75% +/- 5% (mean +/- standard distribution) of the total histamine content. G-CSF priming induced an increase in the chemiluminescence response by up to 50% +/- 5% from human PMN and an increase in histamine release from human LMB by 20% +/- 5%. The growth factors, GM-CSF and G-CSF, modulated neither beta-glucuronidase release from human PMN nor IL-8 release from human PMN and LMB challenged with the E. coli alpha-hemolysin. GM-CSF and G-CSF pretreatment increased the fluoride (NaF)-induced chemiluminescence response by up to 10-fold; the serine/threonine phosphatase inhibitor okadaic acid inhibited GM-CSF- and G-CSF-induced priming. NaF-induced histamine release was enhanced up to 60 and 30% by GM-CSF and G-CSF priming, respectively. GM-CSF and G-CSF pretreatment did not modulate phorbol 12-myristate 13-acetate-induced chemiluminescence response or histamine release. GM-CSF by itself induced an increase in 5-lipoxygenase-specific mRNA expression within 5 min. Our results indicate that (i) GM-CSF and G-CSF interact with inflammatory cells via distinct cellular signalling, (ii) the signal transduction pathway is dependent on the cellular mediator, and (iii) the use of growth factors may be a potent tool to influence the clinical outcome in infectious diseases.
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PMID:Effect of growth factors on Escherichia coli alpha-hemolysin-induced mediator release from human inflammatory cells: involvement of the signal transduction pathway. 751 12

We studied mRNA expression of the cytokine granulocyte-colony stimulating factor (G-CSF), interleukin-1 beta (IL-1 beta), IL-6, IL-8 and stem cell factor of stromal cells derived from bone marrows of nine normal volunteers, eight patients with aplastic anaemia (AA) and seven patients with myelodysplastic syndrome (MDS). The proportion of endothelial cells, macrophages, fibroblast-like cells and adipocytes in stromal cells showed no differences between normal volunteers and the patients. Levels of cytokine mRNA expression were determined by reverse transcription-polymerase chain reaction. Spontaneous expression occurred and this was augmented by LPS stimulation in cells of all the normal volunteers and in most patients. When stimulated by LPS, the mean G-CSF and IL-1 beta mRNA expressions in patients with AA were significantly higher than normal volunteers, but there was one patient showing lower IL-1 beta, IL-6 and IL-8 expression with no response to LPS. LPS-induced IL-6 and IL-8 expression of two patients with MDS were significantly higher than normal. The spontaneous and LPS-induced protein concentration of G-CSF, IL-6 and IL-8 in culture supernatants from 15, 10 and four patients, correlated well with the mRNA expression. The correlation coefficients were 0 x 92, 0 x 78 and 0 x 91, respectively. In conclusion, there were a few patients whose aetiology appeared to be reduction of stromal cytokine expression in AA, but most patients with AA and MDS expressed normal or high levels of cytokine mRNA.
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PMID:Cytokine mRNA expression of bone marrow stromal cells from patients with aplastic anaemia and myelodysplastic syndrome. 752 19

Recent studies have shown that eosinophils are capable of generating and releasing cytokines, providing a novel biologic aspect of eosinophils for regulating allergic inflammation by an autocrine or paracrine mechanism. Eosinophils synthesize various cytokines; however, the physiologic stimuli that trigger eosinophils to generate cytokines have not been fully elucidated. We examined the effect of chemotactic agonists on eosinophil cytokine generation by employing the determination of IL-8 as the main parameter. Both C5a and FMLP stimulated eosinophils to release IL-8, whereas platelet-activating factor and C-C chemokines did not exert any significant effects. On a molar basis, C5a was two orders of magnitude more potent than FMLP. The generation of IL-8 by chemoattractants was absolutely dependent on the presence of cytochalasin B. Pertussis toxin completely attenuated C5a- and FMLP-induced IL-8 production, indicating the involvement of pertussis toxin-sensitive G-proteins in the signal-transduction process leading to these responses. Experiments of in situ hybridization and PCR amplification revealed that both C5a and FMLP promoted eosinophil IL-8 production through transcriptional gene activation. Pyrrolidine dithiocarbamate completely abrogated chemoattractant-induced IL-8 production, indicating the involvement of NF-kappa B in the cytoplasmic/nuclear signal-transduction process. Furthermore, chemoattractant-induced cytokine production was not limited to IL-8; C5a and FMLP but not platelet-activating factor induced significant secretion of granulocyte-macrophage-CSF from eosinophils. These results indicate that C5a and FMLP stimulate eosinophils to elaborate cytokines, which could be an important mechanism in the regulation of allergic inflammation.
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PMID:Chemotactic agonists induce cytokine generation in eosinophils. 752

In this paper we describe the case of a 16-year-old boy with childhood onset cyclic neutropenia (CN) with a 21 d cycle who was successfully treated with recombinant granulocyte-colony stimulating factor (G-CSF). Cyclic therapy with G-CSF (5 micrograms/kg/d s.c. for 1 week every 21 d) maintained peripheral neutrophil count above the normal range, reduced the incidence of severe infections and significantly improved the patient's performance status throughout an 18-month follow-up. Phenotypic analysis of circulating lymphocytes demonstrated that G-CSF treatment does not modify the phenotypic profile of circulating B, T and NK cell populations. Circulating neutrophils released normal amounts of cytokines (including IL-1 beta, IL-8, TNF alpha) and superoxide anion during G-CSF therapy.
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PMID:Childhood onset cyclic neutropenia: G-CSF therapy restores neutrophil count but does not influence superoxide anion and cytokine release by neutrophils. 753 83

We explored the ex vivo alteration in the cytokine release of stimulated blood taken from healthy volunteers treated subcutaneously with 480 micrograms granulocyte colony-stimulating factor (G-CSF). In a double-blind, controlled, randomized study with 21 volunteers who received G-CSF once or twice 24 hours apart, we measured lipopolysaccharide (LPS)-inducible release of various cytokines and soluble receptors at different times after treatment. At day 1 after a single dose of G-CSF, mediator release was also initiated with muramyl dipeptide, Staphylococcus aureus enterotoxin A, lipoteichoic acid, streptolysin O, complement factor C5a, phytohemagglutinin, or phorbol myristate acetate. In blood from G-CSF-treated subjects, our major findings were (1) a maximal 12-fold increase in interleukin-1 receptor antagonist (IL-1ra) release and an increase of both the p55 and p75 soluble tumor necrosis factor (TNF) receptors; (2) a reduction in TNF release when using all the various stimuli described except LPS; (3) an increase in G-CSF and, to lesser extent, in IL-6, IL-8, and IL-10 release; and (4) an attenuation of interferon-gamma (IFN-gamma) and granulocyte-macrophage (GM)-CSF release. Our findings demonstrate that the major effect of G-CSF treatment is a change in the responsiveness of blood towards a variety of stimuli, which we interpret as a shift toward an antiinflammatory cytokine response.
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PMID:Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers. 753 16


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