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)

Infection and injury are frequently accompanied by hemolysis. Endothelial cells are direct targets of free Hb or its oxidative derivatives, including methemoglobin (MHb) and hemin. This study tested whether Hb or its derivatives alter chemokine (IL-8) and cytokine (IL-6) production and the membrane expression of cell adhesion molecule (E-selectin) in human umbilical vein endothelial cells (passages 2-4, HUVECs). E-selectin membrane content and IL-6 and IL-8 release were quantified by ELISA; cellular mRNA levels were determined by RT-PCR. MHb in vitro resulted in a dose (1-50 microM)- and time (2-16 h)-dependent increase in E-selectin membrane content and IL-6 and IL-8 release in HUVECs. The stimulatory effect of MHb (12 microM) on E-selectin membrane expression and IL-6 and IL-8 release was similar to that produced after treatment with TNF-alpha (5 ng/ml) and IL-1beta (0.25 ng/ml). In contrast, Hb or hemin had no effects. As expected, MHb, Hb, and hemin markedly induced heme oxygenase-1 expression in HUVECs. Haptoglobin, cytochalasin D, and actinomycin inhibited the MHb-induced responses, whereas zinc protoporphyrin IX (a heme oxygenase inhibitor) or desferroxamine (an iron chelator) did not inhibit MHb-induced responses. MHb also increased cellular mRNA levels of E-selectin, IL-6, and IL-8. MHb treatment activated cellular NF-kappaB and NF-kappaB inhibitors; N-acetyl cysteine, SN50, and caffeic acid phenylethyl ester inhibited the MHb-induced responses. These data indicate that MHb is a potent activator of endothelial cells through NF-kappaB-mediated upregulation of cell adhesion molecule expression and chemokine and cytokine production. MHb-induced endothelial cell activation may have clinical significance after infections, hemolysis, or methemoglobinemia.
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PMID:Methemoglobin is a potent activator of endothelial cells by stimulating IL-6 and IL-8 production and E-selectin membrane expression. 1283 37

Infection of cells with influenza A virus results in cell death with apoptotic characteristics. Apoptosis is regarded as a non-inflammatory process. However, during influenza an inflammatory response occurs in the airway epithelium. An examination of this apparent paradox was made using influenza A virus infection of human nasal and bronchiolar epithelial cells. Some cytokine genes (IL-18, CCL2 and CCL5) were expressed constitutively in nasal cells but no cytokine was released. In bronchiolar cells, IL-1 beta, IL-6 and CXCL8 expression was constitutive, whilst CCL2 and CCL5 expression was upregulated following influenza virus infection. IL-6, CXCL8 and CCL5 were released but IL-1 beta and CCL2 were not. In bronchiolar cells, cell death was inhibited by the caspase-8 (Z-IETD-fmk) and pan-caspase (Z-VAD-fmk) inhibitors and these inhibitors enhanced expression of CCL5 and increased the levels of the three secreted cytokines significantly. Thus, the amount of each cytokine released from bronchiolar cells is reduced during cell death, implying that the observed inflammatory response in influenza would be greater if cell death did not occur. Reduced cytokine release is also associated with fragmentation of the Golgi body, as the caspase inhibitors also rescued influenza A virus-induced fragmentation of the Golgi ribbon.
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PMID:Influenza A virus-induced apoptosis in bronchiolar epithelial (NCI-H292) cells limits pro-inflammatory cytokine release. 1291 60

Cytokines play an important role in controlling the homoeostasis of the immune system. Infection with HIV results in dysregulation of the cytokine profile in vivo and in vitro. During the course of HIV-1 infection secretion of T-helper type 1 (Th1) cytokines, such as interleukin (IL)-2, and antiviral interferon (IFN)-gamma, is generally decreased, whereas production of T helper type 2 (Th2) cytokines, IL-4, IL-10, proinflammatory cytokines (IL-1, IL-6, IL-8) and tumour necrosis factor (TNF)-alpha, is increased. Such abnormal cytokine production contributes to the pathogenesis of the disease by impairing cell-mediated immunity. A number of cytokines have been shown to modulate in vitro HIV-1 infection and replication in both CD4 T lymphocytes and cells of macrophage lineage. HIV-inductive cytokines include: TNF-alpha, TNF-beta, IL-1 and IL-6, which stimulate HIV-1 replication in T cells and monocyte-derived macrophages (MDM), IL-2, IL-7 and IL-15, which upregulate HIV-1 in T cells, and macrophage-colony stimulating factor, which stimulates HIV-1 in MDM. HIV-suppressive cytokines include: IFN-alpha, IFN-beta and IL-16, which inhibit HIV-1 replication in T cells and MDM, and IL-10 and IL-13, which inhibit HIV-1 in MDM. Bifunctional cytokines such as IFN-gamma, IL-4 and granulocyte-macrophage colony-stimulating factor have been shown to have both inhibitory and stimulatory effects on HIV-1. The beta-chemokines, macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES are important inhibitors of macrophage-tropic strains of HIV-1, whereas the alpha-chemokine stromal-derived factor-1 suppresses infection of T-tropic strains of HIV-1. This review outlines the interactions between cytokines and HIV-1, and presents clinical applications of cytokine therapy combined with highly active antiretroviral therapy or vaccines.
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PMID:Cytokines and HIV-1: interactions and clinical implications. 1295 22

Infection of cervical keratinocytes by high-risk HPV is involved in the etiology of cervical carcinoma. Since viral products are immunogenic, development of cancer may require suppression of immune responses directed against infected epithelial cells. Many markers of host immune effector responses decrease as cervical intraepithelial neoplasia progresses. Among these is epithelial cell expression of the chemokine MCP-1, though the mechanism for its suppression is unclear. Here, we show that the E6 and E7 viral oncogenes from high-risk HPV, individually and together, suppress MCP-1 expression in primary epithelial cells derived from the female genital tract. This is not a consequence of global suppression of chemokine expression since other chemokines, including IP-10, IL-8 and RANTES, were less affected. Furthermore, 4 of 6 HPV-positive cervical carcinoma cell lines did not express MCP-1. Our data indicate that suppression of MCP-1 expression is part of the program of high-risk HPV E6/E7-induced transformation of primary epithelial cells. These observations are consistent with a model in which MCP-1 expression by infected keratinocytes, which would stimulate an immune attack on HPV-transformed cells, is suppressed for invasive cervical cancer to appear.
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PMID:Selective suppression of monocyte chemoattractant protein-1 expression by human papillomavirus E6 and E7 oncoproteins in human cervical epithelial and epidermal cells. 1450 41

Airway epithelial cells are unresponsive to endotoxin (lipopolysaccharide (LPS)) exposure under normal conditions. This study demonstrates that respiratory syncytial virus (RSV) infection results in increased sensitivity to this environmental exposure. Infection with RSV results in increased expression of Toll-like receptor (TLR) 4 mRNA, protein, and increased TLR4 membrane localization. This permits significantly enhanced LPS binding to the epithelial monolayer that is blocked by disruption of the Golgi. The increased TLR4 results in an LPS-induced inflammatory response as demonstrated by increased mitogen-activated protein (MAP) kinase activity, IL-8 production, and tumor necrosis factor alpha production. RSV infection also allowed for tumor necrosis factor alpha production subsequent to TLR4 cross-linking with an immobilized antibody. These data suggest that RSV infection sensitizes airway epithelium to a subsequent environmental exposure (LPS) by altered expression and membrane localization of TLR4. The increased interaction between airway epithelial cells and LPS has the potential to profoundly alter airway inflammation.
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PMID:Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin. 1456 59

Cryptosporidium parvum is an obligate intracellular protozoan capable of causing life-threatening diarrhoeal disease in immunocompromised individuals. Efforts to develop novel therapeutic strategies have been hampered by the lack of understanding of the pathogenesis of infection. To better understand the host response to C. parvum infection, gene expression profiles of infected human ileocecal adenocarcinoma cells were analysed by using Affymetrix oligonucleotide microarrays containing probe sets for 12,600 human genes. Statistical analysis of expression data from three independent experiments identified 223 genes whose expression was reproducibly regulated by C. parvum infection at 24 h post-inoculation (125 up-regulated and 98 down-regulated), 13 of which were validated by quantitative reverse transcriptase polymerase chain reaction analysis. This analysis revealed the consistent up-regulation of host heat-shock genes and genes for pro-inflammatory chemokines IL-8, RANTES, and SCYB5. Multiple genes for host actin and tubulin genes were up-regulated whereas genes for actin binding proteins were down-regulated, confirming previous observations of host cytoskeleton rearrangement in response to C. parvum infection. In addition, host genes associated with cell proliferation and apoptosis were differentially regulated, reflecting the complexity of host-parasite interaction. Together, this study demonstrated that C. parvum infection results in significant changes in host biochemical pathways and provides new insights into specific biological processes of infectious disease caused by an intracellular protozoan parasite.
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PMID:Cryptosporidium parvum regulation of human epithelial cell gene expression. 1471 92

Several radiopharmaceuticals are currently used for diagnosis of inflammatory and infectious diseases in patients. Most inflammatory and infectious processes can be visualized with radiolabeled autologous leukocytes, currently considered to be the most appropriate radiopharmaceutical for this purpose. This agent is very well capable to delineate most inflammatory and infectious foci in a relatively short time after injection. The time-consuming and intricate labeling procedure and the handling of potentially contaminated blood, however cause that there is a great interest in the development of new radiopharmaceuticals comprising the same imaging qualities but without these disadvantages. Besides radiolabeled leukocytes several other radiopharmaceuticals, such as (67)Ga-citrate, radiolabeled anti-granulocyte antibodies and FDG are used to image infection and inflammation. These agents accumulate in infectious and inflammatory lesions in a non-specific manner or have suboptimal diagnostic characteristics. Nowadays, there is a great interest in the development of radiolabeled chemotactic and chemokinetic cytokines that accumulate and are retained in infectious and inflammatory foci by specific interaction with infiltrated inflammatory cells. In this review we describe the specific characteristics of the chemotactic and chemokinetic compounds that are currently studied as potential radiopharmaceutical to visualize infectious and inflammatory foci. The characteristics of a series of cytokines (IL-1, IL-2), chemokines (IL-8, PF-4, MCP-1, NAP-2), complement factors (C5a, C5adR), chemotactic peptides (fMLF) and other chemotactic factors (LTB4) are described. The potentials of these compounds to serve as an imaging agent are discussed.
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PMID:Radiolabeled chemotactic cytokines: new agents for scintigraphic imaging of infection and inflammation. 1497 17

Differentiation of hematopoietic stem cells (HSCs) can be influenced by different stimuli, including cytotoxic agents, certain cytokines, and contact with pathogens. Infection may result in dysregulation of these important progenitor cells and therefore interfere with the availability of blood cells. In this study we analyzed the effect of bacterial infection on HSCs concerning surface marker expression and cytokine release. Listeria monocytogenes and Yersinia enterocolitica accelerated maturation of hematopoietic progenitor cells along the myeloid lineage, as demonstrated by the upregulation of CD13, CD14, and costimulatory signals. By screening cytokine secretion, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-6, IL-8, IL-10, IL-12, and tumor necrosis factor-alpha were found to be induced by bacterial infection. These data indicate that infection of HSCs with L. monocytogenes and Y. enterocolitica affects the differentiation of CD34(+) hematopoietic progenitors in vitro and may lead to secretion of cytokines that can influence the HSC differentiation capacity and immune response.
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PMID:Bacterial infection of human hematopoietic stem cells induces monocytic differentiation. 1498 33

Infection with Shiga toxin (Stx)-producing Escherichia coli can lead to development of hemolytic uremic syndrome (HUS). Patients with severe HUS often exhibit central nervous system (CNS) pathology, which is thought to involve damage to brain endothelium, a component of the blood-brain barrier. We hypothesized that this neuropathology occurs when cerebral endothelial cells of the blood-brain barrier, sensitized by exogenous TNF-alpha and stimulated by Stx1, produce and release proinflammatory cytokines. This was tested by measuring changes in cytokine mRNA and protein expression in human brain endothelial cells (hBEC) in vitro when challenged by TNF-alpha and/or Stx. High doses of Stx1 alone were somewhat cytotoxic to hBEC; Stx1-treated cells produced increased amounts of IL-6 mRNA and secreted this cytokine. IL-1beta and TNF-alpha mRNA, but not protein, were increased, and IL-8 secretion increased without an observed increase in mRNA. Cells pretreated with TNF-alpha were more sensitive to Stx1, displaying greater Stx1-induction of mRNA for TNF-alpha, IL-1beta, and IL-6, and secretion of IL-6 and IL-8. These observations suggest that in the pathogenesis of HUS, Stx can induce cytokine release from hBEC, which may contribute toward the characteristic CNS neuropathology.
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PMID:Escherichia coli Shiga toxin 1 and TNF-alpha induce cytokine release by human cerebral microvascular endothelial cells. 1500 Dec 24

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)-gamma, inflammatory cytokines interleukin (IL)-1, IL-6 and IL-12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)-alpha, anti-inflammatory cytokine IL-10, Th1 cytokine IL-2 and Th2 cytokine IL-4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-gamma-inducible protein-10 (IP-10). Corticosteroid reduced significantly IL-8, MCP-1 and IP-10 concentrations from 5 to 8 days after treatment (all P < 0.001). Together, the elevation of Th1 cytokine IFN-gamma, inflammatory cytokines IL-1, IL-6 and IL-12 and chemokines IL-8, MCP-1 and IP-10 confirmed the activation of Th1 cell-mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.
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PMID:Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. 1503 May 7


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