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)

Visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) are the major parasitic diseases in which the immune system is implicated in pathogenesis. The in vitro production of interleukin (IL)-2, IL-4, IL-6, IL-8, tumor necrosis factor-alpha (TNF alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF), spontaneously and in response to stimulation of peripheral blood mononuclear cells with anti-CD3, phytohemagglutinin, and lipopolysaccharide, was investigated to determine their importance in VL and CL. Highly enhanced production of IL-4, IL-6, IL-8, and TNF alpha was seen in VL. However, enhanced production of IL-4 and TNF alpha but almost normal production of IL-6 and IL-8 was seen in CL. The highly increased IL-4 production was the most characteristic and common feature of both VL and CL. Of interest, highly deficient GM-CSF production may be implicated in abnormalities in synthesis of hematopoietic lineage of cells in these diseases.
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PMID:Immunoregulatory and proinflammatory cytokine production in visceral and cutaneous leishmaniasis. 793 Jul 2

Inflammatory cytokines, including interleukin (IL)-1 alpha, IL-1 beta, IL-8, and tumor necrosis factor alpha (TNF-alpha) are produced by macrophages in response to a variety of pathogenic stimuli. We show here that the expression of inflammatory cytokines is suppressed by IL-4 at the transcriptional level. Interleukin-4, when added together with bacterial lipopolysaccharide (LPS), suppressed LPS-induced increases in mRNA levels of IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha in alveolar macrophages. The level of suppression was dependent on dose and time of exposure and reached a maximum of 75-80% of uninduced values for IL-1 alpha, IL-8, and TNF. Interleukin-1 beta expression was completely inhibited by IL-4. The amount of secreted protein, as determined by TNF-alpha bioassay, was also suppressed by IL-4. Half-maximal suppression occurred at IL-4 concentrations between 0.02 and 0.1 ng/ml for all inflammatory cytokines. Nuclear run-on assays showed that IL-4 suppressed transcriptional activity of all inflammatory cytokines. Messenger RNA stability was not changed by IL-4. The data suggest that IL-4 plays an important transcriptional role in the regulation of alveolar macrophage inflammatory activities in respiratory disease and raise the possibility that IL-4 may function in vivo as a coordinator of inflammatory and immune responses.
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PMID:Interleukin-4 suppresses inflammatory cytokine gene transcription in porcine macrophages. 793 Sep 48

Concentrations of MCP-1 and NAP-1 in culture fluids of human leukocytes were measured by sandwich ELISA. PPD caused PBMC's from tuberculin-sensitive subjects to secrete MCP-1 and NAP-1. PPD did not stimulate secretion by cells from a tuberculin-negative subject. Since the amounts secreted were more than could be produced by the few PPD-sensitized lymphocytes in the culture, we postulate that other cells were stimulated to secrete these chemoattractants. This study evaluated secretory capacity of one of the cell types in the PBMC culture. Unstimulated monocytes did not secrete MCP-1 or NAP-1. In order of increasing effect, IL-2 + IFN gamma, IL-1 alpha, and LPS caused monocyte secretion of MCP-1. The rank order for NAP-1 secretion was the same. TNF alpha did not cause secretion of MCP-1, but caused about the same amount of NAP-1 secretion as IL-2 + IFN gamma. Composition of the culture medium was especially critical for LPS-induced secretion of MCP-1, which was greatly enhanced by FCS and by Iscove's DMEM compared to RPMI 1640. IL-4 inhibited LPS-induced secretion of both MCP-1 and NAP-1. Secretory patterns were also a function of mononuclear phagocyte phenotype. LPS-induced secretion of MCP-1 was much greater for monocytes cultured several days in CSF-1 than for freshly isolated monocytes. LPS stimulation of bronchoalveolar macrophages caused NAP-1 secretion, but no secretion of MCP-1 above a relatively low baseline level.
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PMID:Secretion of monocyte chemoattractant protein-1 (MCP-1) by human mononuclear phagocytes. 794 99

The interleukin-2 (IL-2) receptor gamma is an indispensable functional component of IL-2, IL-4, and IL-7 receptors, and thus, is denoted the common gamma chain, gamma c. The present study was undertaken to determine whether human polymorphonuclear neutrophils (PMNs) expressed gamma c chain. Reverse transcription-polymerase chain reaction and Northern blot analysis showed that fresh human PMN constitutively expressed a remarkable level of gamma c mRNA, which is of the size and intensity of that from the peripheral blood mononuclear cells (PBMCs). Granulocyte macrophage-colony stimulating factor, IL-2, and IL-8, which are known to activate PMN functions, failed to regulate the gamma c gene expression. Western blot analysis with a rabbit anti-gamma c polyclonal antibody identified 64-, 58-, and 50-kD gamma c bands in lysates from PMN, but only 64- and 58-kD bands from PBMCs. After the PMNs and PBMCs were treated with tunicamycin to prevent N-linked glycosylation, Western blot analysis detected a single 39-kD band, which is equal to the calculated molecular weight from the cloned cDNA. Thus, our results indicate that PMNs constitutively express high levels of gamma c and the three forms detected are caused by different glycosylation of a protein translated from a single mRNA species.
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PMID:Expression of interleukin-2 receptor gamma chain on human neutrophils. 794 44

IL-4, a product of the T-helper 0 (Th0) and 2 (Th2) subset, was originally described as a B-cell stimulatory factor and has subsequently been found to suppress IL-1 alpha, IL-1 beta, IL-6, IL-8, and TNF-alpha gene expression in monocytes stimulated with LPS, and to upregulate IL-1 receptor antagonist (IL1-RA) gene expression. In this study we investigated the effect of IL-4 on the expression of cytokine genes in monocytes evoked by other T-helper cell cytokines: IL-2, IL-3, and GM-CSF. IL-4 down-regulated mRNA accumulation of the proinflammatory cytokines IL-1 beta, IL-8, and TNF-alpha in monocytes stimulated with IL-2, IL-3, and GM-CSF. IL-4 also suppressed the IL-2-induced IL-6 mRNA expression. Temporal analysis of the IL-4 down-regulatory effect on the IL-2-, IL-3-, or GM-CSF-induced proinflammatory cytokine gene expression in monocytes provided evidence that IL-4 acts predominantly on the post-transcriptional level. This was supported by the observation that the down-regulatory capacity of IL-4 appeared to be dependent on de novo protein synthesis. IL-4 did not exert significant influence on the induction of expression of IL-1-RA or various CSFs by IL-2, IL-3, and GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IL-4 down-regulates IL-2-, IL-3-, and GM-CSF-induced cytokine gene expression in peripheral blood monocytes. 803 34

Cytokines have a central role in the generation of an autoimmune response and can directly affect the target organ. In Graves' disease, both the infiltrating mononuclear cells and the thyroid follicular cells produce certain cytokines, but the relative contribution of each is unclear, and there are conflicting data on the exact profile of cytokines expressed within the thyroid. To clarify these issues, we used the method of reverse transcription-polymerase chain reaction amplification to analyze cytokine gene expression by intrathyroidal lymphocytes (ITL) and purified thyroid follicular cells (TFC) from six patients with Graves' disease. All ITL samples were positive for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF alpha) messenger ribonucleic acids (mRNAs). Four samples were positive for IL-2 mRNA, and of these, three were also positive for interferon-gamma (IFN gamma). All TFC samples contained IL-6 and IL-8 mRNAs, even after depletion of CD3-positive T-cells. One TFC sample was additionally positive for IL-10 and TNF alpha mRNAs, and in the case of IL-10, this signal was not eliminated by CD3-positive T-cell depletion. IL-4 was not detected in any sample of ITL, TFC, or whole tissue. Semiquantitative analysis showed that the ITL fraction represented the major source of IL-6, IL-8, and TNF alpha mRNAs. By contrast, only three of five multinodular goiter samples were positive for IL-1 alpha mRNA; of these, two were also positive for IL-6, and 1 was positive for IL-8 mRNA. One multinodular goiter sample was positive for IL-8 mRNA alone, but IL-2, IL-4, IL-10, and TNF alpha mRNAS were not detected. These results suggest that although the TFC themselves may express certain cytokines, the ITL population represents the most important source of cytokine production in Graves' thyroid glands. The presence of IL-2, IFN-gamma, and TNF alpha and the absence of IL-4 mRNA in samples of ITL indicate a pattern of cytokine production that most closely resembles that of the TH1 helper T-cell subset. Given the etiological role of thyroid-stimulating antibodies in Graves' disease, the production of which is likely to depend upon TH2 helper T-cell function, it is perhaps surprising that the TH1 subset appears to predominate. It is possible that IL-10 is important in stimulating intrathyroidal autoantibody production, and this cytokine may also play a role in inhibiting cell-mediated thyroid injury in Graves' disease.
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PMID:Analysis of cytokine gene expression in Graves' disease and multinodular goiter. 804 47

To assess whether RAS oncogenes may affect the expression of cytokines in tumor cells, the presence of interleukins (IL) 1 alpha, 1 beta, 4, 6, 7, and 8, tumor necrosis factor (TNF) alpha and interferon gamma mRNA has been analyzed by reverse transcriptase-polymerase chain reaction in 19 melanoma clones derived from the metastatic cell line 665/2 and previously characterized for RAS mutation and expression. Five of these clones and the parental cell line showed a mutation at codon 61 of N-RAS that resulted in Gln-->Arg substitution (N-RAS/61+), while in the remaining 14, only the wild-type allele for N-RAS was present (N-RAS/61-). With the exception of interferon gamma and IL-4, all the cytokines tested were expressed by the parental 665/2 cell line, whereas IL-1 alpha, IL-6, and TNF-alpha were coordinately transcribed only in the subset of the clones bearing the mutated N-RAS gene. The other cytokine genes studied (IL-1 beta, IL-4, IL-7, and IL-8) displayed a variable degree of expression, and such an heterogeneity was not correlated to the N-RAS phenotype of the clones. The association between N-RAS oncogene and IL-1 alpha, IL-6, and TNF-alpha expression was also found in a 665/2 subline (665/2/5) in which loss of mutated N-RAS genes simultaneously occurred with the loss of IL-1 alpha, IL-6, and TNF-alpha expression. Direct evidence that N-RAS oncogene could influence the pattern of cytokine expression was provided by the coordinate induction of IL-1 alpha, IL-6, and TNF-alpha messenger RNA achieved in N-RAS/61+ transfectants of the N-RAS wild-type melanoma clone 2/21. Furthermore, IL-1 alpha, IL-6, and TNF-alpha could be detected by enzyme-linked immunosorbent assay in the culture medium obtained from N-RAS/61+ melanoma clones as well as from positive transfectants, indicating that lymphokine mRNA expression triggered by the activated N-RAS oncogene lead to a secreted protein. In an N-RAS/61+ melanoma clone, by adding specific antibodies against each cytokine, it was found that soluble IL-1 alpha exerted a positive control on IL-6 mRNA and a negative one on its own expression. In addition, IL-1 alpha and IL-6 were negatively regulated by soluble IL-6 and TNF-alpha.
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PMID:Expression of interleukin 1 alpha, interleukin 6, and tumor necrosis factor alpha genes in human melanoma clones is associated with that of mutated N-RAS oncogene. 806 79

The cytokine production induced by a newly discovered streptococcal exotoxin, MF, and the pyrogenic exotoxins SpeA and SpeB was determined by in vitro stimulation of peripheral blood mononuclear cells (PBMCs) obtained from healthy blood donors. The induction and kinetics of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, gamma interferon, tumor necrosis factor alpha (TNF-alpha), TNF-beta, and granulocyte-macrophage colony-stimulating factor were studied at the single-cell level by use of cytokine-specific monoclonal antibodies and intracellular immunofluorescent juxtanuclear staining. The cytokine-producing cells, with the exception of IL-1-expressing cells, had a characteristic morphology generated by the accumulation of cytokines in the Golgi organelle. MF, SpeA, and SpeB induced a massive gamma interferon and TNF-beta response in 10 to 16% of the PBMCs after 48 to 96 h of cell stimulation. In contrast, IL-2 and TNF-alpha production was detected in only 1 to 3% of the PBMCs. The induction of a lymphocyte TH2 phenotype response, including production of IL-3, IL-4, IL-5, and IL-10, was weak. However, the monokines, IL-1 alpha, IL-1 beta, IL-1 receptor antagonist, and IL-8, were consistently found and gradually produced, peaking at 24 h in approximately 5 to 8% of the PBMCs. MF showed extensive cytokine- and proliferation-inducing capacities equal to those of SpeA and SpeB, which suggests that MF is also a superantigen. A marked interindividual variation could be noted both in the proliferative response and in the cytokine induction of lymphocytes isolated from different individuals, which may be one explanation for the varying clinical severity noticed during group A streptococcal infections.
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PMID:Similar cytokine induction profiles of a novel streptococcal exotoxin, MF, and pyrogenic exotoxins A and B. 806 87

Corticosteroids are the most effective drugs in the management of asthma. However, because of their known side effects and the existence of corticosteroid-resistant patients, there is a need for substitute medications in asthma therapy. Using cell lines, in the present study, the two corticosteroids dexamethasone (Dex), and beclomethasone (Bec), as well as the immunosuppressant cyclosporin A (CsA), and the antimetabolic drug methotrexate (Mtx) were examined in their effect on release of immunoreactive IL-1 beta, IL-2, IL-4, IL-5, and IL-8. THP-1 cells served as a test model for monocytes secreting IL-1 beta and IL-8 upon stimulation by lipopolysaccharide. Jurkat cells were used as a test model for TH1-type T-cells and were stimulated for IL-2 release with a combination of phytohemagglutinin and phorbol myristate acetate. Representing TH2-type T-cells, D10.G4.1 cells challenged by anti-CD3-mAb produced IL-4, and IL-5. Considerable qualitative and quantitative differences in the relative efficacy of the test compounds were found. Following IC50 values (nmol/l) of the test compounds were estimated (IL-1 beta/IL-8/IL-2/IL-4/IL-5): Dex (10.8/35.7/ > 10,000.0/5.1/4.1), Bec (30.9/102.2/8591.4/0.6/0.4), and CsA (318.7/6211.2/2.3/68.2/237.9). Mtx in concentrations up to 10,000.0 nmol/l was completely inactive. It can be concluded that corticosteroids show another inhibition pattern than CsA: corticosteroids affect mainly TH2-type T-cells, while CsA primarily inhibits the TH1-type T-cell response.
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PMID:Effect of corticosteroids, cyclosporin A, and methotrexate on cytokine release from monocytes and T-cell subsets. 807 Oct 57

Langerhans cell histiocytosis (LCH) is characterised by an accumulation of cells ('LCH cells') with the same phenotypic features as normal Langerhans cells found in skin and other organs. The pathogenesis of LCH is unknown but there is increasing evidence to implicate the involvement of lymphokines and proinflammatory cytokines in the tissue damage seen in this disorder. Apart from histiocytes, the lesions contain giant cells, macrophages, neutrophils, eosinophils, lymphocytes, plasma cells and occasional mast cells that are the hallmark of an inflammatory process. The role of cytokines in the recruitment of haemopoietic cells within inflammatory lesions has only recently been recognised. In this article, we review the possible role of cytokines in the pathogenesis of LCH, and provide an overview of the methods currently used to detect and quantitate them. An appreciation of the type, distribution and amount of different cytokines released within lesions can provide clues to the possible aetiology of LCH. Using immunoassays, in situ hybridisation and RT-PCR, increased amounts of IL-1, IL-3, IL-4, IL-8, GM-CSF, TNF alpha, TGF beta and LIF have been demonstrated in LCH lesions. Lymphocytes constitutively produce GM-CSF and IL-3 and, to a lesser degree, IL-1, IL-4 and LIF whilst histiocytes produce TNF alpha, IL-1 beta and GM-CSF.
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PMID:The role of cytokines in the pathogenesis of Langerhans cell histiocytosis. 807 4


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