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)

In this study, we demonstrate that mononuclear cells of human milk have a potential for production of many different cytokines. We applied a technique for cytokine detection at the single-cell level using cytokine specific MAb and immunofluorescence. The characteristic staining pattern obtained represents intracellular cytokine production, which allows for the assessment of the cellular origin of production. Milk mononuclear cells were mitogen-stimulated in vitro and cultured for 4 h and then stained for 13 cytokines. Lipopolysaccharide stimulation induced extensive production of the following monokines: IL-1 alpha, IL-1 beta, IL-1ra, IL-6, IL-8, and tumor necrosis factor-alpha. IL-10 and granulocyte-macrophage colony-stimulating factor were smaller products, although detectable in most samples. The abundant monokine production correlated with the high number of macrophages in milk. Spontaneous monokine production in unstimulated cells could be detected in six out of 11 samples. The highest incidence was evident for IL-8. No spontaneous lymphokine production was detected. Considering the low proportion of lymphocytes, stimulation with phorbol myristate acetate in combination with ionomycin resulted in considerable production of the following lymphokines: IL-2, IL-3, IL-4, IL-10, interferon-gamma, tumor necrosis factor-alpha. Macrophages contributed to the high production of tumor necrosis factor-alpha and GM-CSF. IL-5 synthesis was detectable in only one sample. This work reveals that human milk mononuclear cells are potent producers of cytokines when mitogen stimulated in vitro. The in vivo implications of these findings remain to be investigated further.
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PMID:Cytokine production in mononuclear cells of human milk studied at the single-cell level. 823 27

In recent years, there has been a growing body of evidence suggesting that IL-8 and granulocyte-macrophage CSF (GM-CSF) play an important role in inflammatory processes. We show that after GM-CSF treatment, the exposure of human neutrophils to IL-8 results in the synthesis of leukotriene (LT)B4 and platelet-activating factor. In GM-CSF-treated cells, IL-8 induced a concentration-dependent synthesis of both lipid mediators, with a threshold at 10 to 30 nM, suggesting that IL-8 could stimulate phospholipase A2 activity, an enzyme essential for both syntheses. Accordingly, IL-8 induced a substantial release of 3H-arachidonic acid in GM-CSF-treated PMN. It was also found that IL-8 activates the neutrophil 5-lipoxygenase (5-LO), the other key enzyme in LT biosynthesis. IL-8 induced 5-LO activation in a time- and concentration-dependent manner, with a threshold at 1 nM, and prior treatment of neutrophils with GM-CSF enhanced this effect of IL-8 over the 1 to 300 nM range. Neutrophil-activating peptide-2 and the melanoma growth-stimulatory activity, two peptides that are closely related to IL-8, also had the ability to activate the 5-LO and stimulate LT synthesis, albeit less potently than IL-8. Finally, pertussis toxin and the 5-LO translocation inhibitor, MK-886, both blocked the IL-8-elicited 5-LO activation. Taken together, our results raise the possibility that the combined presence of IL-8 and of GM-CSF at inflammatory foci could result in the synthesis of platelet-activating factor and LTB4 by neutrophils, thereby contributing to the amplification of the inflammatory response.
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PMID:Induction by chemokines of lipid mediator synthesis in granulocyte-macrophage colony-stimulating factor-treated human neutrophils. 824 74

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

Reactive oxygen intermediates (ROIs) are involved in many neurological diseases. Despite the toxic nature of these compounds, low concentrations of ROIs can function as signaling molecules. One target for their signaling function is the inducible transcription factor NF-kappa B. Predominantly in lymphoid cells, induction of NF-kappa B in response to oxidative stress leads to transcriptional activation of many genes which are relevant for pathogen defense. These include the TNF, IL-6, IL-8, GM-CSF, beta-interferon, MHC class I and V-CAM genes. However, NF-kappa B is also abundant in various cell types of the nervous system, including neurons. We propose that NF-kappa B plays a role as a redox-controlled transcriptional activator also in cells of the nervous system and in that property may contribute to neurological disorders. Our finding that some neurons from healthy brain contain constitutively active NF-kappa B suggests a role of NF-kappa B in normal brain function as well.
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PMID:Potential involvement of the transcription factor NF-kappa B in neurological disorders. 826 32

Cryptococcus neoformans, a pathogenic fungus usually acquired by inhalation, causes the most common lethal mycosis in AIDS. The resident lung phagocytes, alveolar macrophages (AM phi), inhibit growth of C. neoformans poorly unless activated by cytokines such as IFN-gamma. In this study, we examined the effect of rat AM phi of the potent hematopoietic and M phi-activating cytokine, granulocyte-macrophage CSF (GM-CSF), alone and in combination with other cytokines. Rat AM phi monolayers were preincubated with 0.1 to 1000 U/ml GM-CSF without or with other recombinant cytokines, and then were incubated with viable C. neoformans (strain H99/C3D). Growth inhibition was assessed by counting cryptococcal CFU at 24 and 48 h of coculture; AM phi proliferation was assessed by measuring both uptake of [3H]TdR and AM phi numbers. AM phi preincubated with GM-CSF for 5 days (but not for shorter periods) inhibited growth of C. neoformans. Anticryptococcal activity required direct contact of AM phi with C. neoformans, but once induced by preincubation, did not require continued exposure to GM-CSF. Induction of anticryptococcal activity by GM-CSF was dose dependent (maximal induction at 250 U/ml), and was due to both increased ingestion and killing. GM-CSF induced AM phi proliferation, but anticryptococcal activity was not due totally to increases in AM phi numbers, indicating AM phi activation by GM-CSF. GM-CSF-induced AM phi proliferation was increased by IL-6, unchanged by IL-8, and abolished by LPS or IFN-gamma. However, IL-6 did not increase GM-CSF-induced anticryptococal activity. The combination of GM-CSF and IFN-gamma showed rapid and sustained anticryptococcal activity, unlike either cytokine alone. Our in vitro data suggest that the combination of GM-CSF and IFN-gamma may have beneficial effects on host defense against C. neoformans in vivo.
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PMID:Effect of granulocyte-macrophage colony-stimulating factor on rat alveolar macrophage anticryptococcal activity in vitro. 828 47

Polymorphonuclear neutrophils (PMN) have long been thought to be short-lived, terminally differentiated cells incapable of synthesizing significant levels of protein, with their primary function being phagocytosis and the release of cytotoxic compounds. More recently, it has been demonstrated that PMN can produce a number of functionally diverse substances, including IL-1, IL-6, and IL-8. Although PMN express class I MHC Ag, it has not been definitely demonstrated that they can synthesize and express class II Ag. This would suggest that, although PMN can indirectly assist in the induction of an immune response through production of cytokines, they are incapable of acting as APC for CD4+ Th cells. We show that, in the presence of a defined medium (AIM V), human serum, and granulocyte-CSF, nearly 100% of isolated PMN can survive for up to 2 days in vitro. We also show that PMN express MHC class II when present as bystander cells in a monocyte/T cell Ag presentation assay for 44 h. In addition, granulocyte/macrophage CSF (GM-CSF), IFN-gamma, and IL-3 can induce class II on pure cultures of PMN, with GM-CSF appearing to be the most potent of the three cytokines. Furthermore, induction of class II on PMN is distinctly donor dependent, with PMN from some donors repeatedly showing very high, and others very low, induction of class II when treated with GM-CSF. Their potential to express class II suggests that PMN could play a significant role in immunoregulation and disease pathogenesis. The variation in class II induction on PMN from individual donors might explain previous failures to detect class II induction on PMN and could be a factor in the varied susceptibility of different individuals to autoimmune and inflammatory disorders such as the production of antibodies to PMN cytoplasmic components.
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PMID:Induction of MHC class II on human polymorphonuclear neutrophils by granulocyte/macrophage colony-stimulating factor, IFN-gamma, and IL-3. 833 42

Prognosis in myelodysplastic syndrome (MDS) is not only correlated closely with blast cell count in bone marrow and chromosomal abnormalities but also correlated with decreased leucocyte count and function leading to acquisition of lethal infections. Recently, clinical trials in MDS have focused on the application of haemopoietic growth factors such as G-CSF or GM-CSF, which have proven to increase neutrophil count and function. However, these cytokines carry the risk of stimulating the malignant clone, particularly in patients with increased blast cell count. Therefore, investigation of cytokines which are able to stimulate neutrophil function without the potential risk of stimulating haemopoietic progenitor cells may be relevant for MDS. As the stimulatory effect of interleukin-8 on neutrophil function is well known, we investigated whether recombinant human IL-8 is also able to improve the function of neutrophils gained from patients with MDS. Using three different techniques--the E. coli killing assay (8 patients), the production of reactive oxygen as determined by cytochrome c reduction (7 patients) and chemiluminescence (8 patients)--a significant stimulation of neutrophil function at a concentration of 10 nm IL-8 was found in all test systems. No correlation with FAB classification was evident. On the other hand, IL-8 only mildly stimulated growth of myeloid progenitor cells in bone marrow culture of healthy individuals and MDS patients. This minimal stimulation was blocked by a neutralizing antibody directed against GM-CSF, suggesting an indirect effect of IL-8 via secondary GM-CSF release. Thus, IL-8 is able in vitro to repair the functional abnormalities of neutrophils from patients with MDS but has only a marginal influence on myeloid progenitor cells.
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PMID:Recombinant human interleukin-8 restores function in neutrophils from patients with myelodysplastic syndromes without stimulating myeloid progenitor cells. 838 40

The activity of four recombinant human cytokines on porcine neutrophils was evaluated. Porcine neutrophils were treated with varying doses of recombinant human tumour necrosis factor-alpha (rHu-TNF), interferon-gamma (rHu-IFN), interleukin-8 (rHu-lL-8), or granulocyte-macrophage colony-stimulating factor (rHu-GM-CSF). The function of treated neutrophils was compared with that of non-treated controls in the following assays: antibody-independent neutrophil cytotoxicity (AINC), antibody-dependent cell-mediated cytotoxicity (ADCC), iodination, Staphylococcus aureus ingestion, cytochrome C reduction, random migration, and chemotaxis. Treatment with rHu-TNF produced significant (P < 0.05) depression of neutrophil random migration (2.5, 25, and 250 ng ml-1 rHu-TNF) and iodination (250 ng ml-1) and a near significant (P = 0.08) depression in ADCC (250 ng ml-1). Treatment with 25,000 U ml-1 of rHu-IFN caused a significant increase in AINC. At lower doses of rHu-IFN, there was a trend (0.05 < P < or = 0.08) toward depression of AINC (250 U ml-1) and ADCC (25 U ml-1) and enhancement of iodination (250 U ml-1). Treatment with 50 ng ml-1 of rHu-IL-8 caused a near significant increase (P = 0.06) in AINC. There were no significant differences noted when porcine neutrophils were treated with rHu-GM-CSF (2.5-2500 U ml-1). No synergism was noted between rHu-TNF and rHu-IFN.
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PMID:Effect of recombinant human cytokines on porcine neutrophil function. 839 2

Fibroblasts play an indirect augmenting effector role in the inflammatory response by releasing growth and differentiation factors and other inflammatory mediators after activation by inflammatory cytokines such as interleukin (IL)-1, but whether direct activation occurs by exogenous agents such as endotoxin (lipopolysaccharide, LPS) remains controversial. Using a number of primary human airways tissue-derived fibroblast lines, we demonstrate that in contrast to IL-1 alpha, LPS significantly induced gene expression and production of granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-8, and IL-6 only in nasal but not bronchial or lung tissue-derived fibroblasts. Enhanced expression was dose- and time-dependent, and the minimal stimulatory dose was 10 ng LPS/ml. Polymyxin B entirely abrogated increased cytokine expression by LPS. Actinomycin D treatment largely inhibited expression, and LPS markedly increased an IL-6 gene promoter-driven luciferase reporter response in transfected nasal fibroblasts, suggesting enhanced expression may involve transcriptional regulation. Secondary protein or IL-1 synthesis requirement seemed unlikely since cycloheximide superinduced LPS-stimulated cytokine expression and anti-IL-1 alpha/beta antibodies failed to abrogate the response. Thus our data show that GM-CSF, IL-8, and IL-6 are directly inducible in nasal fibroblasts by LPS, and establish heterogeneous responsiveness to LPS by different fibroblast populations in the airways.
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PMID:Lipopolysaccharide induces expression of granulocyte/macrophage colony-stimulating factor, interleukin-8, and interleukin-6 in human nasal, but not lung, fibroblasts: evidence for heterogeneity within the respiratory tract. 839 62

Although studies of nitrogen dioxide (NO2) inhalation, in both animals and humans, have demonstrated that this agent can cause epithelial cell damage and inflammation of the airway epithelium, the mechanisms underlying these effects are not well understood. We have cultured human bronchial epithelial cells, as explant cultures from surgical tissue, and studied these firstly from their ability to constitutively synthesize specific proinflammatory cytokines and then investigated the effect of exposure to NO2 on the generation of these cytokines. Constitutive synthesis of cytokines was evaluated by analysis of both the expression of the mRNA for interleukin (IL)-1 beta, IL-4, IL-8, granulocyte/macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), by the polymerase chain reaction (PCR), and by immunocytochemical staining for the presence of cell-associated IL-1 beta, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, using specific monoclonal and polyclonal antibodies directed towards these cytokines. Release of IL-4, IL-8, GM-CSF, TNF-alpha, and IFN-gamma following exposure to 5% CO2 in air or 400 ppb and 800 ppb NO2 for 6 h was investigated by enzyme-linked immunosorbent assay. PCR demonstrated that the human bronchial epithelial cells expressed the mRNA for IL-1 beta, IL-8, GM-CSF, and TNF-alpha but not for IL-4 and IFN-gamma. Immunocytochemical staining confirmed the presence of endogenous IL-1 beta, IL-8, GM-CSF, and TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nitrogen dioxide on synthesis of inflammatory cytokines expressed by human bronchial epithelial cells in vitro. 839 64


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