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)

The interleukin-12 receptor (IL-12R)beta1 chain is an essential component of the functional IL-12R on both human T and natural killer cells. In this report it is shown that activation of human peripheral blood mononuclear cells (PBMC) with anti-CD3 monoclonal antibody (mAb) or phytohemagglutinin resulted in the up-regulation of IL-12Rbeta1 expression and IL-12 binding. Kinetic studies revealed that maximum expression of IL-12Rbeta1 and IL-12 binding occurred on days 3-4. Anti-CD3-induced expression of IL-12Rbeta1 chain and IL-12 binding by PBMC was augmented by anti-CD28 mAb, indicating that the potentiating effect of anti-CD28 on T cell responses to IL-12 could be mediated, at least in part, by the enhancement of IL-12R expression. Among 16 cytokines tested, IL-2, IL-7 and IL-15 markedly induced IL-12Rbeta1 expression and IL-12 binding on resting PBMC, whereas IL-1alpha and tumor necrosis factor-alpha had a minimal enhancing effect. In contrast, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-alpha, IFN-gamma, granulocyte/macrophage colony-stimulating factor and transforming growth factor (TGF)-beta2 had no detectable enhancing effect. Anti-CD3-induced expression of IL-12Rbeta1 and of low-affinity IL-12 binding sites was partially inhibited by TGF-beta2, IL-10 and IL-4; however, TGF-beta2 and IL-10 completely abolished anti-CD3-induced expression of high-affinity IL-12 binding sites. Consistent with the reduction of high affinity IL-12 binding sites, PBMC activated with anti-CD3 mAb in the presence of TGF-beta2 or IL-10 failed to produce IFN-gamma or to proliferate in response to IL-12. These results suggest that Th2 cell-derived cytokines can inhibit IL-12-induced biological functions by inhibiting IL-12R expression and that expression of a second subunit of the IL-12R (IL-12Rbeta2), required for the formation of high-affinity IL-12 binding sites, may be more highly regulated by TGF-beta2 and IL-10 than is expression of IL-12Rbeta1.
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PMID:Regulation of interleukin-12 receptor beta1 chain expression and interleukin-12 binding by human peripheral blood mononuclear cells. 902 11

Cytokines are a heterogenous group of polypeptide mediators that have been associated with activation of numerous functions, including the immune system and inflammatory responses. The cytokine families include, but are not limited to, interleukins (IL-I alpha, IL-I beta, ILIra and IL-2-IL-15), chemokines (IL-8/ NAP-I, NAP-2, MIP-I alpha and beta, MCAF/MCP-1, MGSA and RANTES), tumor necrosis factors (TNF-alpha and TNF-beta), interferons (INF-alpha, beta and gamma), colony stimulating factors (G-CSF, M-CSF, GM-CSF, IL-3 and some of the other ILs), growth factors (EGF, FGF, PDGF, TGF alpha, TGF beta and ECGF), neuropoietins (LIF, CNTF, OM and IL-6), and neurotrophins (BDNF, NGF, NT-3-NT-6 and GDNF). The neurotrophins represent a family of survival and differentiation factors that exert profound effects in the central and peripheral nervous system (PNS). The neurotrophins are currently under investigation as therapeutic agents for the treatment of neurodegenerative disorders and nerve injury either individually or in combination with other trophic factors such as ciliary neurotrophic factor (CNTF) or fibroblast growth factor (FGF). Responsiveness of neurons to a given neurotrophin is governed by the expression of two classes of cell surface receptor. For nerve growth factor (NGF), these are p75NTR (p75) and p140trk (referred to as trk or trkA), which binds both BDNF and neurotrophin (NT)-4/5, and trkC receptor, which binds only NT-3. After binding ligand, the neurotrophin-receptor complex is internalized and retrogradely transported in the axon to the soma. Both receptors undergo ligand-induced dimerization, which activates multiple signal transduction pathways. These include the ras-dependent pathway utilized by trk to mediate neurotrophin effects such as survival and differentiation. Indeed, cellular diversity in the nervous system evolves from the concerted processes of cell proliferation, differentiation, migration, survival, and synapse formation. Neural adhesion and extracellular matrix molecules have been shown to play crucial roles in axonal migration, guidance, and growth cone targeting. Proinflammatory cytokines, released by activated macrophages and monocytes during infection, can act on neural targets that control thermogenesis, behavior, and mood. In addition to induction of fever, cytokines induce other biological functions associated with the acute phase response, including hypophagia and sleep. Cytokine production has been detected within the central nervous system as a result of brain injury, following stab wound to the brain, during viral and bacterial infections (AIDS and meningitis), and in neurodegenerative processes (multiple sclerosis and Alzheimer's disease). Novel cytokine therapies, such as anticytokine antibodies or specific receptor antagonists acting on the cytokine network may provide an optimistic feature for treatment of multiple sclerosis and other diseases in which cytokines have been implicated.
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PMID:Neurotrophins and their receptors in nerve injury and repair. 910 50

The epidermal response to 2 different irritants, nonanoic acid (NAA) and sodium lauryl sulfate (SLS), was investigated with 2 different methods. NAA 80% and SLS 4% were applied under occlusion for up to 24 h. Elemental changes were determined in cryosections by x-ray microanalysis. Compared to unexposed skin a significantly higher sodium/potassium ratio was found after 6 h in NAA-exposed skin and a lower ratio in SLS-exposed. At 24 h both substances had induced similar changes, compatible with a cell injury. The findings demonstrate a time-dependent NAA and SLS response. With reverse transcription polymerase chain reaction, the mRNA expression of interleukin-1 alpha (IL-1 alpha), -1 beta (IL-1 beta), -6 (IL-6), and -8 (IL-8), tumor necrosis factor alpha (TNF alpha) and granulocyte macrophage colony stimulating factor (GM-CSF) in shave biopsies from irritated and unexposed skin was studied at 0. 4. 8 and 24 h. NAA, but not SLS, induced an increase in mRNA expression for IL-6 mRNA-expression for GM-CSF was increased after SLS exposure, but not after NAA. These findings indicate a time and substance dependent difference in the up-regulation of mRNA for different cytokines in epidermis during the first 24 h of the irritant reaction. This might be the effect of differences in the irritants action on the cell membranes, which is also reflected by the differences found in the elemental content at 6 h.
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PMID:Different pathways in irritant contact eczema? Early differences in the epidermal elemental content and expression of cytokines after application of 2 different irritants. 911 30

Adenovirus E1A DNA and proteins are frequently detected in lungs of patients with chronic obstructive pulmonary disease. Because adenovirus E1A can regulate host gene expression by interacting with cellular transcription factors, we postulate that E1A enhances synthesis of inflammatory mediators. To examine this possibility, we measured the expression of inflammatory cytokines in E1A-producing A549 human pulmonary epithelial cells and control cells. Interleukin (IL)-8 mRNA was markedly induced by lipopolysaccharide (LPS) in E1A-producing cells but not in controls. IL-8 protein levels were elevated in parallel. In both cell types, monocyte chemotactic and activating factor mRNA induced by LPS was low, and transforming growth factor-beta 1 mRNA was not affected. IL-1 beta, IL-6, granulocyte macrophage colony-stimulating factor, and granulocyte colony-stimulating factor mRNAs were too low to show any effect of E1A. We conclude that the LPS responsiveness of A549 pulmonary epithelial cells is altered by adenoviral E1A by upregulating IL-8. We speculate that this mechanism may be important in the amplification of the inflammatory process of lungs to other irritants.
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PMID:Adenovirus E1A upregulates interleukin-8 expression induced by endotoxin in pulmonary epithelial cells. 922 2

Eosinophilia is a feature of nasal polyposis. The aim of this study was to determine the role of cytokines and allergen in maintaining the eosinophilic infiltrate in this condition. Polyp fragments from house dust mite (HDM)-sensitive atopic individuals and nonatopic individuals were cultured in the presence of HDM, or phytohaemagglutinin (PHA) or culture medium alone. Culture supernatants were assayed for interleukins (IL) 3, 5, and 8 and granulocyte macrophage colony stimulating factor (GM-CSF), and eosinophil survival enhancing activity (ESEA) in vitro. Significant ESEA was produced spontaneously. When polyp tissue from atopics, but not from nonatopics, was stimulated with allergen for 2 days there was a further increase in ESEA associated with a median 12 and fourfold increase in IL-8 and GM-CSF, respectively. This increased ESEA was markedly reduced with anti-GM-CSF and, to a lesser extent, anti-IL-8 blocking antibodies. When stimulated with PHA, polyp tissue from atopic subjects also produced increased ESEA, implicating possible T-cell involvement. This was associated with a small (twofold), but significant, increase in IL-8 and a less consistent increase in GM-CSF. However, anti-IL-8 or anti-GM-CSF blocking antibodies failed to reduce the ESEA in these supernatants, suggesting involvement of other mechanisms. This study suggests that in sensitized individuals, allergen may contribute to polyp eosinophilia by stimulating the production of granulocyte/macrophage colony stimulating factor and interleukin 8.
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PMID:Allergen-induced release of GM-CSF and IL-8 in vitro by nasal polyp tissue from atopic subjects prolongs eosinophil survival. 923 Feb 33

In type 1 Gaucher disease, decreased activity of glucocerebrosidase results in accumulation of glucosylceramide in macrophages. Infiltration of liver, spleen and bone marrow by lipid-laden macrophages leads to hepatosplenomegaly, bone lesions and cytopenia. These abnormal macrophages may produce and release macrophage derived factors and cytokines, which could contribute to the pathophysiology of the disease. Whether these cytokines and factors are elevated in Gaucher disease is currently unknown. In 29 type 1 Gaucher disease patients we measured serum levels of the macrophage derived cytokines IL8, IL6, TNFalpha, M-CSF and the monocyte/macrophage activation marker sCD14. These factors were studied in relation to disease severity and during treatment with enzyme supplementation therapy. Most patients showed remarkably elevated levels of M-CSF (2-8 fold) and sCD14 (2-5 fold) as compared to normal controls. Levels of IL8 were elevated in all patients (2-20 fold), whereas levels of IL6 and TNFalpha were normal. There was a significant correlation between severity of the disease as determined by the severity score index (SSI), and M-CSF, sCD14 and IL8 levels. M-CSF and sCD14 levels also correlated with the excess liver and spleen volumes. During treatment with alglucerase, levels of M-CSF and sCD14 declined, but IL8 remained unchanged. The relative reduction in excess liver and spleen volume did not correlate with the relative reduction in M-CSF or sCD14 levels. We conclude that serum levels of M-CSF, sCD14 and IL8 are increased in type 1 Gaucher disease. The biological activities of M-CSF and IL8 may add to the pathophysiology of the disease.
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PMID:Elevated levels of M-CSF, sCD14 and IL8 in type 1 Gaucher disease. 923 58

The inflammatory reaction in the human gastric mucosa to Helicobacter pylori could be initially triggered by an array of cytokines expressed in infected gastric epithelial cells. The spiral morphology and flagella of these organisms could increase their velocity in a viscous environment such as methylcellulose solution. The goal of this study was to determine whether modification of H. pylori motility could influence the expression of cytokine genes from gastric epithelial cells infected with H. pylori. Adherent human gastric epithelial cells were cultured and overlaid with methylcellulose solutions of varying viscosity. These epithelial cell layers covered with methylcellulose solution were inoculated with H. pylori. RNAs were then extracted from the gastric epithelial cells. Various cytokine gene expressions were assessed and quantified by reverse transcription-polymerase chain reaction (RT-PCR) and standard synthetic RNA. Cytokine proteins were also measured by enzyme-linked immunosorbent assay (ELISA). Expression of mRNA for interleukin(IL)-8 was upregulated in H. pylori-infected gastric epithelial cells overlaid with methylcellulose of 15 centipoise (cp) viscosity. The expression of mRNA for IL-1 alpha, IL-8, monocyte chemotactic protein (MCP)-1 and granulocyte macrophage colony-stimulating factor (GM-CSF) was also upregulated in H. pylori-infected gastric epithelial cells overlaid with methylcellulose solution of the same viscosity. The number of molecules of the expressed cytokine transcripts also paralleled the amounts of protein secreted from gastric epithelial cells infected with H. pylori. These results suggest that methylcellulose solution (simulating the mucus layer in vivo) could increase contact of H. pylori with gastric epithelial cells by increasing its motility. This could result in the upregulation of mRNA for proinflammatory cytokines in gastric epithelial cells, therefore enhancing inflammatory reaction at H. pylori-infected sites.
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PMID:Increased motility of Helicobacter pylori by methylcellulose could upregulate the expression of proinflammatory cytokines in human gastric epithelial cells. 923 62

Inflammatory cells infiltrate the liver in response to microbial infection or hepatic injury. To assess the potential role hepatocytes may play in initiating or amplifying the acute inflammatory response in the liver, we used three human hepatocyte cell lines and primary human hepatocyte cultures to characterize the repertoire of cytokines that can be expressed and regulated in hepatocytes in response to agonist stimulation or bacterial infection. As reported herein, a proinflammatory cytokine gene program that includes C-X-C and C-C chemokines [interleukin-8(IL-8), growth related (GRO)-alpha, GRO-beta, GRO-gamma, epithelial neutrophil activating peptide-78 (ENA-78), and RANTES] and the cytokines tumor necrosis factor-alpha (TNF-alpha) and macrophage colony stimulating factor was upregulated in human hepatocytes after stimulation with IL-1 alpha or TNF-alpha or bacterial invasion. In contrast, expression of hematopoietic/ lymphoid growth factors by the same cells was either down-regulated (erythropoietin and stem cell factor) or unchanged (IL-7 and IL-15) in response to the identical stimuli. Hepatocytes did not express cytokines that often are associated with the regulation of antigen-specific immune responses (IL-2, IL-4, IL-5, IL-10, IL-12p40, IL-13, and interferon-gamma) or genes for several other proinflammatory cytokines [IL-1 alpha, IL-6, monocyte chemotactic protein-1 (MCP-1), and MCP-3] or hematopoietic growth factors (granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, IL-3, and IL-11). Together, these studies suggest that hepatocytes can both initiate and amplify acute inflammatory responses in the liver through the regulated expression and secretion of a specific array of proinflammatory cytokines.
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PMID:Human hepatocytes express an array of proinflammatory cytokines after agonist stimulation or bacterial invasion. 927 10

To elucidate the role of hematopoietic growth factors (HGFs) and other cytokines in the autocrine or paracrine regulation of inducible hematopoiesis we studied cytokine gene expression in the bone marrow (BM) of patients after myelosuppressive treatment. Furthermore, we studied the cytokine gene expression profile in healthy individuals before and after bone marrow harvesting for the purpose of bone marrow transplantation. We speculated that the bone marrow harvesting procedure might induce changes in cytokine gene expression. No induction of G-CSF, GM-CSF, IL-1 alpha, IL-3, IL-5, IL-8, IL-9, and IL-12 was observed in the BM of patients following intensive chemotherapy. Also, no up-regulation of expression of M-CSF, IL-1 beta, IL-4, IL-6, TNF-alpha, TGF-beta, IGF-1, EDF, and EPA gene was found, illustrating that the investigated cytokines probably are not relevant in the presumed autocrine/paracrine regulation of the recovery of hematopoiesis following depletion of hematopoietic progenitor cells (HPCs). Concomitantly, elevated G-CSF plasma levels were found in these patients, suggesting that G-CSF has an endocrine regulatory role in inducible hematopoiesis. Induction of GM-CSF and IL-8, but not of G-CSF or IL-3 gene expression and upregulation of IL-1 beta and IL-6 gene following BM harvesting was observed. This induction of GM-CSF and IL-8 may be attributed to tissue damage rather than to HPC depletion.
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PMID:The role of cytokines and hematopoietic growth factors in the autocrine/paracrine regulation of inducible hematopoiesis. 932 80

Leukaemia inhibitory factor (LIF) acts on the growth and differentiation of haematopoietic cells. By using a specific enzyme-linked immunosorbent assay for human LIF, we demonstrate that human bone marrow stromal cells produce LIF. LIF synthesis is enhanced in a dose-dependent manner after stimulation with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMAS). LIF production in response to PMA is PKC-dependent since the two PKC inhibitors sphingosine and staurosporine markedly diminished it. Interleukin 1alpha (IL-1alpha), IL-1beta, IL-3, IL-6, IL-8, tumour necrosis factor (TNF-alpha) and SCF (both at 10 ng/ml) stimulate LIF production. By contrast macrophage colony-stimulating factor (M-CSF), granulocyte (G)-CSF, GM-CSF, basic fibroblast growth factor (bFGF), platelet-activating factor (PAF), protaglandin E2 (PGE2), leukotriene B4 (LTB4), and leukotriene C4 (LTC4) did not. These results suggest that bone marrow stromal cells might represent a major source for the cytokine-regulated local production of LIF inside human bone marrow.
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PMID:Spontaneous and inducible production of leukaemia inhibitory factor by human bone marrow stromal cells. 934 7


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