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)

Surfactant protein A (SP-A) and lactoferrin (LF) play important roles in innate immune systems in the respiratory mucous membranes. We investigated how SP-A and LF act against respiratory syncytial virus (RSV) infection. The present study indicated that RSV-induced IL-8 secretion from HEp-2 cells was up-regulated by SP-A (170% of control) but down-regulated by LF (23% of control). RSV infectivity determined by viral titers and the uptake of FITC-labeled RSV were also increased by SP-A, but decreased by LF. To clarify the mechanism of these opposite effects, we examined the interactions of SP-A and LF with RSV F protein, the most important surface glycoprotein for viral penetration. RSV F protein was found to be the ligand for both SP-A and LF, but the manners of binding were different. LF directly interacted with the F(1) subunit, which involved antigenic sites of F protein. Contrarily, SP-A associated with the F(2) subunit, which was highly glycosylated. SP-A but not LF failed to interact with deglycosylated F protein. Moreover, SP-A initiated the hemolyzing fusion activity of F protein. These results suggest that SP-A and LF modulate RSV infection by different binding specificity to F protein.
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PMID:Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection. 1451 73

Glycoprotein hormone receptors (GPHRs) differ from the other seven transmembrane receptors mainly through a complex activation mechanism that requires the binding of a large hormone toward a large N-terminal ectodomain. The intramolecular mechanism of the signal transduction to the serpentine domain upon hormone binding at the ectodomain is not understood. To identify determinants at the GPHR ectodomain that may be involved in signal transduction, we first searched for homologous structural features. Based on high sequence similarity to the determined structures of the Nogo-receptor ectodomain and the intermolecular complex of the Interleukin-8 ligand (IL8) and the N-terminal peptide of the IL8 receptor (IL8RA), the hypothesis was developed that portions of the intramolecular components, Cysteine-box-2 and Cysteine-box-3, of the GPHR ectodomain interact and localize at the interface between ectodomain and serpentine domain. Indeed, point mutations within the D403EFN406 motif at Cysteine-box-3 of the thyrotropin receptor resulted in increased basal cAMP levels, suggesting that this motif may be important for transduction of the signal from the ectodomain to the transmembrane domain. New indications are provided about the tight spatial cooperation and relative location of the new epitope and other determinants at the thyrotropin receptor ectodomain, such as the leucine-rich repeat motif Ser281 and the cysteine boxes. According to the high sequence conservation, the results are of general relevance for the signal transduction mechanism of other glycoprotein hormone receptors such as choriogonadotrophic/luteinizing hormone receptor and follicle-stimulating hormone receptor.
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PMID:Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface. 1534 20

In acute myeloid leukemia (AML), cell proliferation and differentiation are uncoupled, causing a maturation block. Induction of terminal differentiation is a potential therapeutic strategy. 1alpha, 25(OH)2 Vitamin D3 regulates differentiation and is immunomodulatory at concentrations causing severe hypercalcemia, thus limiting its use. We investigated 1alpha, 25(OH)2 Vitamin D3 and 5 of its more potent analogs with reduced calcium resorbing activity for differentiation of blast cells from AML (FAB M1) patients, compared to TPA. Blast phenotype, p-glycoprotein expression, cytokine production, and lineage specificity were examined. The Vitamin D3 analogs had no effect on cell viability and proliferation. They induced incomplete differentiation, with increase in AP, NSE and NBT positivity of cells, but no cell sticking and spreading as observed with TPA. The analogs were more effective than the parent compound. They also inhibited the production of IL-6 and IL-8. Vitamin D3 and its analogs can induce differentiation of primary cells from AML patients in vitro, but may need to be combined with other agents for terminal differentiation of blasts and effective therapy in vivo.
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PMID:Effect of 1,25(OH)2 Vitamin D3 analogs on differentiation induction and cytokine modulation in blasts from acute myeloid leukemia patients. 1537 Feb 59

Respiratory syncytial virus (RSV) is worldwide the single most important respiratory pathogen in infancy and early childhood. The G glycoprotein of RSV, named attachment protein, is produced by RSV-infected lung epithelial cells in both a membrane-anchored (mG protein) and a soluble form (sG protein) that is secreted by the epithelial cell. Currently, the biological role of the sG protein in primary RSV infection is still elusive. Therefore, we analyzed the inflammatory response of human lung epithelial cells (A549) infected either with wild-type RSV (RSV-WT) or a spontaneous mutant thereof deficient in the production of secreted G protein (RSV-DeltasG). Our data reveal that RSV-DeltasG, in comparison to RSV-WT, induced an increased cell surface expression of ICAM-1 on A549 cells and an enhanced release of the chemokines IL-8 and RANTES after 20 h postinfection. The increased protein expression pattern correlated with an enhanced mRNA level encoding for ICAM-1, IL-8, and RANTES, respectively. Furthermore, epithelial cells infected with RSV-DeltasG showed a more increased binding activity of the transcription factor NF-kappaB when compared to RSV-WT. In contrast, the mutant RSV-DeltasG replicated less efficiently in A549 cells than RSV-WT. Our data suggest that RSV, in the course of an ongoing infection, reduces by the production of sG protein the detrimental inflammatory response evolved by the infected resident lung epithelial cell and thereby supports its own replication.
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PMID:Respiratory syncytial virus deficient in soluble G protein induced an increased proinflammatory response in human lung epithelial cells. 1556 33

Ebola virus, a member of the family Filoviridae, causes one of the most severe forms of viral hemorrhagic fever. In the terminal stages of disease, symptoms progress to hypotension, coagulation disorders, and hemorrhages, and there is prominent involvement of the mononuclear phagocytic and reticuloendothelial systems. Cells of the mononuclear phagocytic system are primary target cells and producers of inflammatory mediators. Ebola virus efficiently produces four soluble glycoproteins during infection: sGP, delta peptide (Delta-peptide), GP(1), and GP(1,2Delta). While the presence of these glycoproteins has been confirmed in blood (sGP) and in vitro systems, it is hypothesized that they are of biological relevance in pathogenesis, particularly target cell activation. To gain insight into their function, we expressed the four soluble glycoproteins in mammalian cells and purified and characterized them. The role of the transmembrane glycoprotein in the context of virus-like particles was also investigated. Primary human macrophages were treated with glycoproteins and virus-like particles and subsequently tested for activation by detection of several critical proinflammatory cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], and IL-1 beta) and the chemokine IL-8. The presentation of the glycoprotein was determined to be critical since virus-like particles, but not soluble glycoproteins, induced high levels of activation. We propose that the presentation of GP(1,2) in the rigid form such as that observed on the surface of particles is critical for initiating a sufficient signal for the activation of primary target cells. The secreted glycoproteins do not appear to play any role in exogenous activation of these cells during Ebola virus infection.
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PMID:Role of Ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages. 1568 42

Since previous results showed that interleukin 8 (IL-8) was induced in rainbow trout (Oncorhynchus mykiss) in response to viral hemorrhagic septicemia virus (VHSV) infection, we have cloned IL-8 in an expression vector (pIL8+) and studied its possible adjuvant effect on the early response to a VHSV immunization model, focusing on the early response of several cytokines induced by a vector coding for the glycoprotein of VHSV (pMCV1.4-G) in the spleen and head kidney. First, we demonstrated that the pIL8+ successfully transcribed IL-8, by induction of IL-8 transcription in the muscle and blood, and by a massive infiltration of neutrophils at the muscle inoculation site. We have studied the effect of pIL8+ co-administration on the expression of two pro-inflammatory cytokines, such as IL-1beta and tumour necrosis factor alpha (TNF-alpha); cytokines that have mainly an inhibitory role, IL-11 and transforming growth factor beta (TGF-beta); and a Th1 type cytokine, IL-18. We demonstrated that the co-administration of pIL8+ with pMCV1.4-G modulates the cytokine response that is induced, mainly by having its effect increasing pro-inflammatory cytokines (IL-1beta and TNF-alpha1), with a greater impact on the spleen, and to a lesser extent in the head kidney. All these data suggest that IL-8 is able to modulate the early cytokine immune response that is produced in response to a DNA vaccine, and therefore, might be a potential immune adjuvant in fish viral vaccination. More work should be done to determine if this modulation has a beneficial effect on protection as seen in other mammal viral models.
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PMID:Co-injection of interleukin 8 with the glycoprotein gene from viral haemorrhagic septicemia virus (VHSV) modulates the cytokine response in rainbow trout (Oncorhynchus mykiss). 1672 33

In rainbow trout (Oncorhynchus mykiss), at least three CXC chemokines and eighteen CC chemokine sequences have been discovered in the past years, although no studies concerning their bioactivity have been performed yet. We have studied the expression of five different CC chemokines that cluster into the group of inducible chemokines (CK5A, CK5B, CK6, CK7A and CK7B) in trout injected with a plasmid coding for the glycoprotein G gene (pMCV1.4-G) of viral haemorrhagic septicemia virus (VHSV). In a previous work, we had demonstrated that a plasmid coding for the CXC chemokine interleukin 8 (IL-8, pIL8+) when co-administered with pMCV1.4-G was able to modulate the expression of induced pro-inflammatory cytokines, therefore, we have also studied the expression of these inducible CC chemokines in fish injected with pMCV1.4-G in the presence of pIL8+, study that will also help establish the relations among the different chemokine groups. All chemokines were induced in the head kidney of fish injected with the DNA vaccine, and the co-administration of pIL8+ together with the vaccine modulated the expression of all CC chemokines studied. In this sense, expression of the inducible CC chemokines was also studied in trout head kidney leucocytes treated with supernatants from EPC cells transfected with pIL8+. In this case, all CC chemokines studied except for CK5B were significantly induced by rainbow trout IL-8.
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PMID:Expression of inducible CC chemokines in rainbow trout (Oncorhynchus mykiss) in response to a viral haemorrhagic septicemia virus (VHSV) DNA vaccine and interleukin 8. 1728 35

The recent molecular characterization and sequencing of equine P-selectin (ePsel), and its glycoprotein ligand, P-selectin glycoprotein ligand-1 (PSGL-1), have provided the tools for further investigation into their role in leukocyte trafficking. Here, we report the generation of a genetically engineered chimeric protein (ePsel-IgG) in which the equine P-selectin lectin and epithelial growth factor (EGF) domains were covalently linked to the equine IgG1 heavy chain constant region. The soluble ePsel-IgG was observed to bind to equine monocytes by confocal microscopy and flow cytometry. Furthermore, equine monocytes bound to immobilized ePsel-IgG in a time course and dose dependent manner. Not only did ePsel-IgG act as an adhesion molecule, it was also found to activate ERK1/2 kinase and induce IL-8 mRNA expression in equine monocytes. That all of the aforementioned ePsel-IgG-induced cell binding and cell signaling were abolished by the addition of EDTA, suggested that ePsel-IgG chimera mediated events occurred via the P-selectin ligand, PSGL-1. We were able to demonstrate that 78% of equine monocytes cross-reacted with anti-human HECA-452 antibody, which recognizes the sialy-Lewis X (sLex) epitope, a well-known carbohydrate binding site on human PSGL-1. Pre-incubation of equine PBMC with neuraminidase or O-sialoglycoprotein endopeptidase (OSGP) reduced ePsel-IgG monocyte binding to 36% or 60%, respectively. Taken together, these data suggest that there might be two ligand recognition sites on P-selectin, one of which recognizes sLex and another which recognizes P-selectin ligand core protein. The ePsel-IgG chimera can be a useful as a reagent for further studies on the role of equine P-selectin and signal transduction in inflammatory events in horse.
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PMID:Cloning and functional characterization of recombinant equine P-selectin. 1730 78

Lactoferrin (LF) is a cationic iron-binding glycoprotein that is abundantly expressed and secreted from glandular epithelial cells and a prominent component of the secondary granules of polymorphonuclear neutrophils. Various in vitro and in vivo experiments demonstrate anti-microbial, -viral, -mycotic and -inflammatory effects of LF, associated with modulations of the immune system. Effects of oral administered LF on selected immune system parameters were studied in calves. Five calves were fed LF beginning on day 3 of life with colostral milk and starting on day 6 of life milk replacer enriched with 0.16% LF was fed. The average daily intake of LF per calf was 1.5-1.6 g/day. Additional five calves served as control group with identical treatment except for the LF supplementation. At the end of the study (day 61 of life), all calves were slaughtered and various tissues were sampled for histological and gene-expression studies. LF given orally was shown to act as an immunomodulatory agent by enhancing the size of Peyer's patches in the ileum and increasing blood serum immunoglobulin G levels. In addition, the number of peripheral blood leucocytes increased and mRNA levels of various interleukins (IL) such as IL-1beta, IL-8, IL-10 and interferon gamma (IFNgamma) in those cells in response to LF treatment were enhanced. In blood, the mRNA expression of the pro-inflammatory marker genes IL-1beta and IFNgamma decreased over 10-week treatment. Additionally, LF feeding decreased villus sizes in the jejunum. Together these findings emphasize the ability of LF to stimulate prominent immune system parameters and that it has the capacity to modulate the immune responses in a positive way.
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PMID:Effect of lactoferrin on selected immune system parameters and the gastrointestinal morphology in growing calves. 1735 40

The recognition of bacterial lipopolysaccharide (LPS) is principally mediated by either membrane-bound or soluble form of the glycoprotein CD14 and CD14-associated signal transducer, toll-like receptor 4 (TLR4). Recent findings indicate that the serine protease inhibitor, alpha1-antitrypsin (AAT), may not only afford protection against proteolytic injury, but may also neutralize microbial activities and affect regulation of innate immunity. We postulated that AAT affects monocyte responses to LPS by regulating CD14 expression and soluble CD14 release. Here we show that a short-term (up to 2h) monocyte exposure to AAT alone or in combination with LPS leads to a remarkable induction of CD14 levels. In parallel, a short-term (2h) cell exposure to AAT/LPS significantly enhances LPS-induced NF kappaB (p50 and p65) activation in conjunction with increased TNFalpha, IL-1 beta and IL-8 release. In contrast, longer term incubation (18 h) of monocytes with combined AAT/LPS results in a significant reduction in expression of both CD14 and TLR4, inhibition of LPS-induced TNFalpha, IL-1 beta and IL-8 mRNA and protein expression. These findings provide evidence that AAT is an important regulator of CD14 expression and release in monocytes and suggest that AAT may be involved in LPS neutralization and prevention of over-activation of monocytes in vivo.
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PMID:alpha1-Antitrypsin regulates CD14 expression and soluble CD14 levels in human monocytes in vitro. 1744 22


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