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 CC chemokine monocyte chemotactic protein-1 (MCP-1) was markedly elevated in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-infected patients with cytomegalovirus (CMV) encephalitis. The MCP-1 CSF levels in CMV encephalitis were markedly higher than those in the CSF of HIV-infected patients with or without unrelated neurologic diseases, including progressive multifocal leukoencephalopathy, cryptococcal meningitis, toxoplasmic encephalitis, and primary lymphoma. Interleukin-8, RANTES, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta were not substantially increased in the CSF of CMV encephalitis patients. High levels of MCP-1 may underlie monocyte recruitment and tissue damage in CMV encephalitis and may represent a rapid and useful tool in the diagnostic armamentarium for neurologic disorders associated with HIV infection.
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PMID:Selective elevation of monocyte chemotactic protein-1 in the cerebrospinal fluid of AIDS patients with cytomegalovirus encephalitis. 889 15

The majority of synovial fluids from 29 rheumatoid arthritis patients were strongly attractive for normal blood lymphocytes judged by assays of polarization and collagen gel invasion. While rheumatoid synovial fluids contained IL-15, IL-8, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) at levels sufficient to attract lymphocytes, inhibition of the activity of any single cytokine using specific antibody did not abolish the activity of the fluid. However combinations of anti-cytokine antibodies used together (anti-IL-15+anti-MCP-1; anti-IL-8+anti-MCP-1 or +anti-MIP-1 alpha) inhibited most of the activity, suggesting that attraction of lymphocytes by the fluids is due to a combination of attractants. Blood lymphocytes required activation by overnight culture to respond optimally, while rheumatoid synovial tissue lymphocytes responded to synovial fluids without a requirement for a period of culture. Lymphocytes derived from rheumatoid synovial fluids were poorly responsive to locomotor stimulants. Most of the responding cells from blood mononuclear cell fractions were T lymphocytes of the CD45RO isotype. Incubation in the presence of cyclosporin A or corticosteroids inhibited the response of lymphocytes to the fluids, but the presence of non-steroidal anti-inflammatory drugs (NSAIDs) and other agents used in therapy of the patients from whom the fluids were taken had no inhibitory effect.
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PMID:The chemoattractant activity of rheumatoid synovial fluid for human lymphocytes is due to multiple cytokines. 891 67

The neuroectodermally-derived retinal pigment epithelium (RPE) forms part of the blood-retina barrier where it is strategically-positioned to regulate leukocyte infiltration in retinal diseases. Activated human RPE cells possess several functions enabling them to perform this role including expression of HLA-DR antigens, production of intercellular adhesion molecule-1, and secretion of monocyte chemotactic protein-1 and interleukin-8. In this study, we examined the ability of interleukin-7 to induce RPE-derived monocyte chemotactic protein-1 and interleukin-8 and assessed the potentiating effects of interleukin-7 on interleukin-1 beta- and tumor necrosis factor-alpha-induced RPE monocyte chemotactic protein-1 and interleukin-8 production. Human RPE cells incubated with interleukin-7 (1-100 ng ml-1) for 24 hr secreted significant levels of antigenic RPE monocyte chemotactic protein-1 and interleukin-8 in a dose-dependent fashion interleukin-7 (P < 0.05). RPE costimulation with interleukin-7 and interleukin-1 beta (2 ng ml-1) or tumor necrosis factor-alpha (2 ng ml-1) resulted in additive increases (P < 0.05) in secreted monocyte chemotactic protein-1 and interleukin-8. Steady-state RPE monocyte chemotactic protein-1 mRNA was substantially increased by interleukin-7 (1-100 ng ml-1), while RPE interleukin-8 mRNA was mildly elevated by higher doses of interleukin-7 (10-100 ng ml-1). Time-dependent increases in RPE monocyte chemotactic protein-1 and interleukin-8 mRNA were noted. RPE monocyte chemotactic protein-1 mRNA peaked at 2 hr and decreased over 8 hr and 24 hr. Whereas, RPE interleukin-8 mRNA was perceptible at 2 hr, maximal at 8 hr, and reduced by 24 hr. Interleukin-7 potentiated interleukin-1 beta-induced monocyte chemotactic protein-1 and interleukin-8 steady-state mRNA expression at all interleukin-7 concentrations. Interleukin-7 potentiated tumor necrosis factor-alpha-induced RPE monocyte chemotactic protein-1 steady-state mRNA expression at all doses of interleukin-7 while only high dose interleukin-7 (100 ng ml-1) enhanced tumor necrosis factor-alpha-induced RPE interleukin-8 steady-state gene expression. Our data show that interleukin-7 is a primary stimulus of RPE monocyte chemotactic protein-1 and interleukin-8. This is one of the first reports demonstrating: (1) interleukin-7 induction of monocyte chemotactic protein-1 in any cell type, and (2) interleukin-7 induction of interleukin-8 in resident, tissue-based cells. These studies suggest that interleukin-7 potentiation of interleukin-1 beta and tumor necrosis factor-alpha-induced RPE monocyte chemotactic protein-1 and IL-8 may be important for the elicitation of leukocyte chemotaxins in diseased retinal tissue when only low ambient levels of individual pro-inflammatory cytokines are present.
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PMID:Interleukin-7 (IL-7) induces retinal pigment epithelial cell MCP-1 and IL-8. 894 2

Chemokines bind and signal through G-protein coupled seven transmembrane receptors. Various chemokine receptors are expressed on leukocytes, and these may impart selective homing of leukocyte subsets to sites of inflammation. Human eosinophils express the eotaxin receptor, CCR3, but respond to a variety of CC chemokines apart from eotaxin, including RANTES, monocyte chemotactic protein (MCP)-2, MCP-3, and MCP-4. Here we describe a mAb, 7B11, that is selective for CCR3 and has the properties of a true receptor antagonist. 7B11 blocked binding of various radiolabeled chemokines to either CCR3 transfectants, or eosinophils. Pretreatment of eosinophils with this mAb blocked chemotaxis and calcium flux induced by all CCR3 ligands. In all individuals examined, including allergic and eosinophilic donors, > 95% of the response of eosinophils to eotaxin, RANTES, MCP-2, MCP-3, and MCP-4 was shown to be mediated through CCR3. The IL-8 receptors, particularly CXCR2, were induced on IL-5 primed eosinophils, however these eosinophils responded to CC chemokines in the same manner as unprimed eosinophils. These results demonstrate the importance of CCR3 for eosinophil responses, and the feasibility of completely antagonizing this receptor.
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PMID:Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody. 900 85

Chemokines, together with adhesion molecules, cytokines, and proteases, are essential for the directional migration of leukocytes during normal and inflammatory processes. Interleukin-8 and monocyte chemotactic protein-1 are the best-characterized members of the C-X-C and C-C chemokine subfamilies, respectively. However, more than 20 human chemokines have been identified but are only partially characterized at the biological level. Chemokines are involved in chemotaxis of monocytes, lymphocytes, neutrophils, eosinophils, basophils, natural killer cells, dendritic cells, and endothelial cells. This review describes the chemokine subfamilies, the chemokine producer and target cells, their receptors, signal transduction mechanisms, and the role of chemokines during physiological and pathological conditions. More and more evidence points to a role for chemokines in chemotaxis-related phenomena, such as the expression of adhesion molecules, the secretion of proteinases, inhibition of apoptosis, hematopoiesis, and angiogenesis. Chemokines are also involved in diseases such as cancer (tumor regression and tumor metastasis), autoimmune diseases, and bacterial or viral infection.
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PMID:The role of chemokines in inflammation. 900 10

Activation of T cells in the intestinal mucosa in response to gluten exposure is thought to play a key role in the pathogenesis of coeliac disease. Moreover, the response of the rectal mucosa to gluten challenge has been considered a useful predictor of gluten sensitivity in coeliac disease. In the present study, we assessed early changes in the expression of proinflammatory cytokine genes and the T cell receptor (TCR) Vbeta repertoire in the rectal mucosa of coeliac disease patients following experimental gluten challenge. Cytokine gene expression was assessed in rectal mucosal biopsies from coeliac disease subjects and controls before and after rectal gluten challenge using quantitative reverse transcription polymerase chain reaction analysis, and the TCR Vbeta repertoire was characterized using a multiprobe RNase protection assay. Marked up-regulation of expression of the C-X-C chemokine IL-8, the proinflammatory cytokine IL-1beta, and the C-C chemokine monocyte chemotactic protein-1 occurred within 24 h of rectal gluten challenge in coeliac disease subjects, but not in controls. Furthermore, these changes occurred in the absence of parallel changes in the expressed repertoire of TCR Vbeta genes in the rectal mucosa. Thus, an increased expression of proinflammatory cytokine genes precedes the expansion of antigen-specific T cell populations in the early period following experimental exposure of the rectal mucosa of coeliac disease patients to gluten. These findings provide new insights into pathways that may be involved in the activation or reactivation of coeliac disease.
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PMID:Increased proinflammatory cytokine gene expression in the colonic mucosa of coeliac disease patients in the early period after gluten challenge. 901 Feb 69

The appearance of polymorphonuclear and mononuclear leukocytes in the cerebrospinal fluid (csf) is an important hallmark of bacterial meningitis. Chemokines are candidate mediators of cell migration from blood into the subarachnoid space. Therefore, concentrations of C-X-C and C-C chemokines in the csf of patients with pyogenic meningitis were measured by ELISA. Highly significant elevations of chemokine levels in comparison with noninflammatory csf controls were found for IL-8 (median, 21.6 ng/ml; range, < 0.1 to 191.3), growth-related gene product alpha (median, 5.6 ng/ml; range, < 0.1 to 48.2), monocyte chemotactic protein-1 (median, 26.4 ng/ml; range, < 0.2 to 193.8), macrophage inflammatory protein-1 alpha (MIP-1 alpha; median, 1.8 ng/ml; range, < 0.5 to 18.0), MIP-1 beta (median, 10.6 ng/ml; range, < 0.3 to 84.4), but not for RANTES (regulated upon activation, normal T cell expressed and secreted). The csf of bacterial meningitis were chemotactic for neutrophils and mononuclear leukocytes. Correlation analysis demonstrated a strong association between individual chemokine levels and chemotactic activity mediated by csf. A significant reduction of neutrophil chemotaxis was obtained by anti-IL-8 and anti-growth-related gene product alpha Abs, and a reduction of mononuclear cell migration was achieved by a combination of anti-monocyte chemotactic protein-1, anti-MIP-1 alpha, and anti-MIP-1 beta Abs. Since no significant correlation was found between csf leukocyte counts and chemokine concentrations or chemotactic activity mediated by csf, additional factors influence the extent of pleocytosis in vivo.
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PMID:C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuclear cells in vitro. 902 38

The presence of histamine and eosinophil cationic protein in nasopharyngeal secretions of infants with respiratory syncytial virus (RSV)-induced bronchiolitis implies the activation of basophil and eosinophil leukocytes, but the specific mechanism of their recruitment has not been elucidated. Chemokines are potent and selective leukocyte chemotactic molecules that are also expressed by airway epithelial cells. Therefore, the pattern of chemokines produced in response to RSV infection was investigated in primary cultures of human nose- and adenoid-derived epithelial cells. Interleukin-8, growth-related peptide-alpha, and monocyte chemotactic protein-1 were constitutively released by uninfected epithelial cells and were not further enhanced by infection with RSV. RANTES (regulated upon activation, normal T cell-expressed and -secreted), which was present in negligible concentrations in uninfected cultures, was strongly induced by RSV infection, in a dose- and time-dependent manner. Through the release of RANTES, epithelial cells may control the selective concentration and activation of basophils and eosinophils in RSV-infected airway mucosa.
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PMID:Respiratory syncytial virus induces selective production of the chemokine RANTES by upper airway epithelial cells. 904 19

The chemokine superfamily is a large group of more than 30 small proteins. Many of these were originally identified because of their role in the selective recruitment and activation of leukocytes during inflammation. More recently, some of the chemokine receptors and ligands have been implicated in the mechanism of viral infection for primate lentiviruses such as HIV-1. From the original identification of interleukin-8 (IL-8; the most studied member of the superfamily), the number of new family members has mushroomed over the last few years. Two events have dramatically altered the speed at which sequence information concerning novel chemokines has become available to the scientific community. First, many groups have been obtaining large amounts of sequence information from cDNA libraries by sequencing the clones at random, generating expressed sequence tags (ESTs). Although these ESTs are relatively short, typically less than 500 bases, this amount of sequence is usually sufficient to obtain the entire open reading frame for chemokines. Second, there has been a rapid growth in the use of the WorldWideWeb by bioinformatics groups. The Web was originally set up by the European Centre for Particle Physics (CERN) in Geneva as a method of transferring data between collaborating groups throughout the world. It has enabled biologists throughout the world to have almost instantaneous access both to the databases containing the EST sequences and to the automated tools that are required for searching such databases. With such methods we have been able to rapidly identify more than 10 new human chemokines from public domain databases. In addition to the known categories of chemokines, which are named C, CC, and CXC based on the spacings of N-terminal cysteine residues, we have been able to identify the first member of a novel chemokine subfamily, with a novel CXXXC cysteine spacing. Furthermore, we can subdivide the CC chemokines into monocyte chemotactic protein and macrophage inflammatory protein families based on their sequence identity levels, but also their clustering on the human genome, as identified on other Web sites. The rapid availability of all this data has reduced the amount of time spent on conventional gene identification, enabling us to move quickly on to trying to understand the biology and physiological relevance of these molecules. The novel chemokine sequences obtained and alignments with existing members of the superfamily are now contained within a Chemokine Information Source on an open access server, allowing further searching of chemokine sequences and increasing the availability of such data to the scientific community.
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PMID:The chemokine information source: identification and characterization of novel chemokines using the WorldWideWeb and expressed sequence tag databases. 912 2

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


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