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)

Chemotactic cytokines (chemokines) play an important role in the recruitment of lymphocytes to tissue by regulating cellular adhesion and transendothelial migration. This study examined the expression and function of CXC (human monokine induced by gamma-interferon [HuMig], interleukin-8 [IL-8], and interferon-inducible protein-10 [IP-10]) and CC (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, regulated upon activation normal T lymphocyte expressed and secreted (RANTES), and macrophage chemoattractant protein-1 [MCP-1]) chemokines and their respective receptors on lymphocytes infiltrating human liver tumors. Chemokine and chemokine receptor expression was assessed by immunohistochemistry, flow cytometry, in situ hybridization and ribonuclease (RNAse) protection assays and function by in vitro chemotaxis of tumor-derived lymphocytes to purified chemokines and to HepG2 tumor cell culture supernatants. Tumor-derived lymphocytes showed strong chemotactic responses to both CC and CXC chemokines in vitro and expressed high levels of CXCR3 (HuMig and IP-10 receptor) and CCR5 (RANTES, MIP-1alpha, and MIP-1beta receptor). Expansion of tumor-derived lymphocytes in recombinant IL-2 increased expression of CXCR3. The corresponding chemokines were detected on vascular endothelium (HuMig, IL-8, MIP-1alpha, and MIP-1beta) and sinusoidal endothelium (HuMig, MIP-1alpha, MIP-1beta) in hepatocellular carcinoma. In vitro, HepG2 cells secreted functional chemotactic factors for tumor-derived lymphocytes that could be inhibited using anti-CCR5 or anti-CXCR3 monoclonal antibodies (MoAbs). Thus, lymphocytes infiltrating human liver tumors express receptors for and respond to both CXC and CC chemokines. The relevant chemokine ligands are expressed in hepatocellular carcinoma (HCC), particularly HuMig, which was strongly expressed by tumor endothelium, suggesting that they play a role in lymphocyte recruitment to these tumors in vivo. The ability of HepG2 cells to secrete lymphocyte chemotactic factors in vitro suggests that the tumor contributes to lymphocyte recruitment in vivo.
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PMID:Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma. 1038 45

This report reviews the data presented in the literature concerning the presence and levels of different cytokines in sera, lesional tissue or blister fluids of patients with bullous pemphigoid. The list of cytokines analysed includes 21 molecules: interleukins (IL)-1 => 8, IL-10 => 13, IL-15, granulocyte-monocyte-colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), oncostatin-M (OSM), regulated upon activation normal T cell expressed and presumably secreted (RANTES), transforming growth factor-beta 1 (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF). Basic information regarding the functions of these cytokines and their possible involvement in the pathogenetic steps of the disease, such as autoantigen expression, autoantibody induction, complement activation, local cell recruitment and stimulation, resident cell activation, release of various effector molecules and tissue damage are also reported. A specific function for each cytokine in bullous pemphigoid induction cannot be still defined, however, the literature attributes a major role to IL-1, IL-4, IL-5, IL-6, IL-8 and IFN-gamma. On the basis of significant (direct or inverse) correlations found between disease intensity and the blister fluid/serum levels, the following cytokines IL-7, IL-15, RANTES, VEGF and TNF-alpha, besides those previously mentioned, may also be involved in this disease.
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PMID:Cytokines and bullous pemphigoid. 1040 Aug 17

Chemokines play an important role in the selective movement of leucocytes into inflammatory areas and they also activate various cells in inflamed tissues. However, it is unclear which cells are the main sources of chemokines in actual inflammatory diseases, even though both mononuclear cells and non-inflammatory resident cells are able to produce chemokines in vitro and the former cells are also the main target of chemokines. To clarify the roles of chemokines that are produced by mononuclear cells in AD, we measured levels in vivo of mRNA for IL-8 and MIP-1 alpha, as well as the level of regulated upon activation normal T cell expressed and secreted (RANTES) mRNA in freshly isolated peripheral blood mononuclear cells from patients with AD. We compared the results with those from psoriatic patients, and patients without AD who were suffering from other cutaneous diseases and eosinophilia. Levels of mRNAs were determined by semiquantitative reverse transcriptase-polymerase chain reactions. Levels of IL-8 and MIP-1 alpha mRNA were elevated not only in atopic patients but also in non-atopic patients with inflammatory skin disease associated with eosinophilia, compared with levels in psoriatic patients and healthy controls. Levels of RANTES mRNA were similar in atopic patients but they were lower in the other two groups of patients when compared with levels in healthy controls. In atopic patients, the levels of both IL-8 and MIP-1 alpha mRNAs but not of RANTES mRNA decreased with improvements in symptom scores after therapy. These findings suggest that mononuclear cells are not only the target of chemokines but might also play an important role in the pathogenesis of AD by producing IL-8 and MIP-1 alpha.
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PMID:Increased levels in vivo of mRNAs for IL-8 and macrophage inflammatory protein-1 alpha (MIP-1 alpha), but not of RANTES mRNA in peripheral blood mononuclear cells of patients with atopic dermatitis (AD). 1044 53

Theophylline inhibits eosinophilic infiltration into the bronchial wall. It is unknown whether this is mediated by a cyclic adenosine monophosphate (c-AMP)-dependent reduction in eosinophil chemotactic activity (ECA) from bronchial epithelial cells (BEC). Therefore the effect of a beta2-agonist, procaterol and theophylline on the release of ECA from a BEC line, BEAS-2B was evaluated in response to interleukin (IL)-1beta and tumour necrosis factor-alpha (TNF-alpha). ECA was assessed using a blind-well chemotactic chamber, and the release and gene expression of cytokines were evaluated by means of enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. IL-1beta and TNF-alpha stimulated the release of ECA from BEAS-2B cells in a dose- and time-dependent manner. Procaterol and theophylline directly inhibited eosinophil migration to IL-1beta and TNF-alpha-conditioned medium. The pretreatment of BEAS-2B cells with the same concentrations of procaterol inhibited the release of ECA in a dose-dependent fashion. Anti-IL-8, anti-regulated on activation, normal T-cell expressed and secreted (RANTES), and anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited ECA. Procaterol inhibited the release of RANTES, GM-CSF and IL-8 in a dose-dependent fashion. The effect of theophylline was less potent. Procaterol augmented cAMP levels in BEAS-2B cells in a time- and dose-dependent manner. The expression of IL-8, RANTES, and GM-CSF messenger ribonucleic acid was not inhibited by procaterol and theophylline. These data indicate that procaterol and theophylline may directly inhibit eosinophil migration and that procaterol may further inhibit the release of eosinophil chemotactic activity from BEAS-2B cells via a cyclic adenosine monophosphate-dependent mechanism. This warrants further studies on the involvement of bronchial epithelial cells in the anti-inflammatory effects of procaterol and theophylline in patients with asthma.
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PMID:Procaterol inhibits IL-1beta- and TNF-alpha-mediated epithelial cell eosinophil chemotactic activity. 1057 18

In upper urinary tract infections, tubular epithelial cells (TEC) may play a pivotal role in the initiation of the renal inflammatory response. They exert crucial immunological functions such as processing and presentation of foreign antigen, secretion of proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha) and chemokines (IL-8, MCP-1, ENA-78, and RANTES). Since monolayer cultures are a limited model for polarized tubular epithelial cells, we studied the side-dependent IL-8 secretion of TEC by using cell culture inserts as a basement membrane imitation. Primary cultures of proximal TEC were stimulated with differently fimbriated mutants of Escherichia coli, E. coli LPS, S-fimbria isolates, and IL-1alpha. IL-8 protein was measured by enzyme-linked immunosorbent assay, and IL-8-like biological activity was tested by measuring elastase release from polymorphonuclear cells in supernatants of the upper and lower compartments. IL-8 mRNA was compared by competitive PCR. IL-8 secretion by TEC into the basolateral environment was significantly higher than secretion into the apical compartment, representing the tubular lumen. However, stimulation of IL-8 secretion by TEC was restricted to IL-1alpha and was not inducible by E. coli mutants, S fimbriae, or lipopolysaccharide. With this in vitro model of polarized TEC, we show that luminal contact of TEC with uropathogenic E. coli does not result in enhanced IL-8 secretion. The basolaterally directed production of the neutrophil chemotactic factor IL-8 by TEC after stimulation with IL-1alpha might play an important role in the initiation of inflammatory cell influx into the renal parenchyma.
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PMID:Interleukin-8 secretion of cortical tubular epithelial cells is directed to the basolateral environment and is not enhanced by apical exposure to Escherichia coli. 1060 5

Tissue distribution of dendritic cells was investigated in eight cases of papillary carcinoma of the thyroid using immunohistochemistry. Most dendritic cells had an immature phenotype (CD1a++, CD11c+, CD40+, CD86-, HLA-DR-) and were located at the invasion edge of the tumor. This pattern of distribution was profoundly different from that of CD68+ macrophages, which were evenly distributed throughout the tumor. The ability of tumor cells to release chemotactic factors active on dendritic cells was investigated in primary cultures of the same cases of papillary carcinoma, and was compared to that of the corresponding normal thyroid cells obtained from the tumor-free contralateral lobe. Chemotactic activity of culture supernatants was tested against dendritic cells in a chemotaxis chamber. It was found that papillary carcinoma cells were active in releasing chemotactic activity, that hepatocyte growth factor (HGF; 100 ng/ml) or interleukin (IL)-1beta (10(3) U/ml) induced a fourfold increase in the amount of chemotactic activity released, and that normal thyroid cells obtained from the same patients were as effective as tumor cells. Characterization of chemokines at RNA level revealed that unstimulated cells contain large amounts of IL-8 and monocyte chemotactic protein (MCP)-1 RNAs, and that stimulation with HGF or IL-1beta induced RNAs for regulated upon activation normal T expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-3alpha, interferon-gamma-inducible protein 10 (IP-10), and, to a lesser extent, MIP-1alpha and MIP-1beta. The possibility that HGF/Met interaction has a biological role in vivo was investigated in serial sections of six tumors immunostained for CD1a+, Met protein, and HGF. It was found that all six tumors were intensely and diffusely positive for Met protein, that HGF staining was present in tumor cells of the advancing edge, and that HGF+/Met+ tumor cell nests were infiltrated by CD1a+ dendritic cells. The foregoing observations are consistent with the possibility that HGF stimulation of Met+ tumor cells is one of the molecular mechanisms involved in the recruitment of dendritic cells.
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PMID:Papillary carcinoma of the thyroid: hepatocyte growth factor (HGF) stimulates tumor cells to release chemokines active in recruiting dendritic cells. 1070 99

Nucleic acid immunization has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. Moreover, immune responses induced by DNA immunization can be enhanced by the use of molecular adjuvants. For example, coadministration of costimulatory molecules (CD80 and CD86), proinflammatory cytokines (interleukin-1alpha [IL-1alpha], tumor necrosis factor-alpha [TNF-alpha, and TNF-beta), Th1 cytokines (interleukin-2 [IL-2], IL-12, IL-15, and IL-18), Th2 cytokines (IL-4, IL-5, and IL-10), and granulocytes-macrophage colony-stimulating factor (GM-CSF) with DNA vaccine constructs leads to modulation of the magnitude and direction (humoral or cellular) of the immune responses. To further engineer the immune response in vivo, we compared the induction and regulation of immune responses from the codelivery of chemokine (IL-8, interferon-gamma-inducible protein-10 [gammaIP-10], macrophage inhibitory protein-1alpha [MIP-1alpha], and RANTES) genes with codelivery of cytokine genes. We found that as in cytokine gene codelivery, coimmunization with chemokine genes along with DNA immunogen constructs can modulate the direction and magnitude of induced immune responses. We observed that coimmunization with IL-8, gammaIP-10, and MIP-1alpha genes increased the antibody response. We also found that coinjection with IL-8, gammaIP-10, and RANTES resulted in a dramatic enhancement of T helper (Th) proliferation response. Furthermore, among all coinjection combinations, we found that RANTES coinjection caused a high level of cytotoxic lymphocyte (CTL) enhancement. This enhancement of CTL responses observed from the coinjection with RANTES was CD8+ T cell dependent. Together with earlier reports on the utility of coimmunizing immunologically important molecules with DNA immunogens, we demonstrate the potential of this strategy as an important tool for the development of more rationally designed vaccines.
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PMID:Chemokine gene adjuvants can modulate immune responses induced by DNA vaccines. 1084 Oct 77

We have examined the effect of various chemokines on neuronal toxicity in culture. In mixed cortical cultures, challenged with a brief pulse of N-methyl-D-aspartate (NMDA, 60 microM, 10 min), chemokines were either present for 2 h preceding the pulse or they were co-applied with NMDA and then kept in the medium for the following 20-24 h. Interleukin-8 (IL-8), regulated on activation of normal T cells expressed and secreted (RANTES) and macrophage/monocyte chemoattractant protein-1 (MCP-1), were neuroprotective under both conditions, whereas stromal cell-derived factor 1alpha (SDF-1alpha) was protective only when applied during and after the NMDA pulse. Mixed or pure neuronal cultures were also exposed for 48 h to a toxic fragment of the beta-amyloid peptide (beta-amyloid peptide-(25-35), 12.5 or 25 microM) in the absence or presence of chemokines. Among a number of chemokines, only RANTES was neuroprotective against beta-amyloid peptide-(25-35)-induced neurotoxicity in both cultures. We conclude that activation of chemokine receptors differentially affects neuronal degeneration induced by excitotoxins or beta-amyloid peptide in cortical cultures.
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PMID:Neuroprotective activity of chemokines against N-methyl-D-aspartate or beta-amyloid-induced toxicity in culture. 1088 10

The organic compounds of diesel exhaust particles (DEP-PAHs) have been shown to favor immunoglobulin production and bronchial hyperresponsiveness and to affect cytokine and chemokine productions. To evaluate if diesel exhaust could act in synergy with a house dust mite allergen (Der p 1), peripheral blood mononuclear cells from allergic patients were exposed to DEP-PAHs, with or without purified Der p 1. DEP-PAHs and Der p 1 separately induced an increase in interleukin (IL)-8, regulated on activation, normal T cells expressed and secreted (RANTES), and tumor necrosis factor-alpha concentrations. Interestingly, a synergy between the two stimuli was also observed. In the case of monocyte chemotactic protein (MCP)-1, DEP-PAHs reduced the release, whereas Der p 1 enhanced it. A simultaneous exposure led to reduced production as compared with allergen exposure alone, but still represented an increase as compared with the control exposure. Mitogen-activated protein (MAP) kinase Erk1/2 antagonist mainly inhibited the release of MCP-1, whereas MAP kinase p38 antagonist mainly suppressed the release of IL-8 and RANTES. Messenger RNA expression correlated with protein measurements. Moreover, supernatants from cells exposed to both DEP-PAHs and Der p 1 had a significant chemotactic activity on neutrophils and eosinophils. These findings suggest that simultaneous exposure of allergic patients to DEPs and allergens could result in high local chemokine levels via MAP kinase pathways activation, increasing the likelihood of reaching a critical threshold leading to the initiation of respiratory allergic symptoms.
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PMID:Synergistic effect of diesel organic extracts and allergen Der p 1 on the release of chemokines by peripheral blood mononuclear cells from allergic subjects: involvement of the map kinase pathway. 1091 93

The idiopathic inflammatory myopathies are characterized by antibody- or cell-mediated immune response against unknown muscle tissue antigens. In these diseases a cellular infiltrate, composed of T and B lymphocytes, macrophages and NK cells, may invade muscle tissue with a gradient from the perivascular space to the endomysial compartment. Muscle cells may be actively involved in the processes of mononuclear cell recruitment and activation from the blood stream to the areas of inflammation. In order to verify this hypothesis, cultured human myoblasts were tested for their capacity to express different pro-inflammatory cytokines [IL-1alpha, IL-1beta, IL-6 and tumor necrosis factor (TNF)-alpha] and chemokines (IL-8, MCP-1 and RANTES) at the mRNA level and protein secretion, in the presence of the pro-inflammatory cytokines IFN-gamma and TNF-alpha alone or in combination. We confirmed that human myoblasts expressed IL-1alpha and IL-6 constitutively, while IL-1beta and TNF-alpha are detected only after treatment with pro-inflammatory cytokines; moreover, we observed that TNF-alpha was expressed on an autocrine fashion by myoblasts. IL-8 and RANTES were expressed constitutively while MCP-1 after proper induction. These molecular data were further confirmed by specific ELISA in the supernatant from cultured myoblasts. Our results underline the importance of human myoblasts in the recruitment of leukocytes from the blood stream and, most probably, in the cross-talk between infiltrating inflammatory cells and muscle cells, creating the conditions for a chronic inflammation. Moreover, the capacity of muscle cells to behave as cells of the immune system has to be kept in mind, also in view of i.m. vaccination and use of molecular engineered myoblasts as vehicles in gene therapy.
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PMID:Cytokines and chemokines are both expressed by human myoblasts: possible relevance for the immune pathogenesis of muscle inflammation. 1096 28


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