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 virulence of Entamoeba histolytica is governed by adhesion/colonization in the gut which is mediated by a galactose specific lectin. Two morphologically identical but distinct species i.e. pathogenic E. histolytica and non-pathogenic E. dispar, can be differentiated by distinct epitopes in the lectin. Both species bind to colonic epithelial cells, but only E. histolytica infection induces an inflammatory response and subsequent pathogenesis. Thus, comparing the responses of the intestinal cells to pathogenic and non-pathogenic lectins is a point of interest. The pathogenic lectin causes cytolysis of epithelial and immune-competent cells. Our data (both qualitative and mRNA quantitation) indicate that the epithelial cells responded to E. histolytica lectin with an increased expression of pro-inflammatory IL-2, IL-6, IL-8, MIP-1alpha, MCP-1, RANTES, GROalpha and GMCSF as compared to E. dispar lectin. The pathogenic LCM induced a significant increase in intracellular calcium concentration, proliferative response and chemotaxis of lymphocytes from ALA patients as compared to non-pathogenic LCM. High RANTES and IL-6 were induced in patients' lymphocytes by pathogenic LCM, along with their receptors CCR5 and CD126 as compared to NP-LCM. The local release of such a complex network of cytokines/chemokines could explain the histopathology of E. histolytica infection. The comparative low levels of these chemokines/pro-inflammatory cytokines and high levels of anti-inflammatory IL-10 in response to non-pathogenic E. dispar could explain the absence of an acute inflammatory response and the disease process. The cytokines and chemokines may provide a mechanism for initiation, amplification or containment of inflammation during disease state.
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PMID:Enhanced pro-inflammatory chemokine/cytokine response triggered by pathogenic Entamoeba histolytica : basis of invasive disease. 1633 32

IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1 (pIgA1) and complement. Complement activation via mannose-binding lectin and the lectin pathway is associated with disease progression. Furthermore, recent studies have indicated a possible role for secretory IgA. IgAN is associated with abnormalities in circulating IgA, including aberrant O-linked glycosylation. This study characterized and compared functional properties and N-linked glycosylation of highly purified monomeric IgA (mIgA) and pIgA from patients with IgAN and control subjects. Total serum IgA was affinity-purified from patients (n = 11) and control subjects (n = 11) followed by size separation. pIgA but not mIgA contained secretory IgA, and its concentration was significantly higher in patients with IgAN than in control subjects. Both in patients with IgAN and in control subjects, IgA binding to the GalNAc-specific lectin Helix Aspersa and to mannose-binding lectin was much stronger for pIgA than for mIgA. Furthermore, binding of IgA to mesangial cells largely was restricted to polymeric IgA. Binding of pIgA to mesangial cells resulted in increased production of IL-8, predominantly with IgA from patients with IgAN. Quantitative analysis of N-linked glycosylation of IgA heavy chains showed significant differences in glycan composition between mIgA and pIgA, including the presence of oligomannose exclusively on pIgA. In conclusion, binding and activation of mesangial cells, as well as lectin pathway activation, is a predominant characteristic of pIgA as opposed to mIgA. Furthermore, pIgA has different N-glycans, which may recruit lectins of the inflammatory pathway. These results underscore the role of pIgA in glomerular inflammation in IgAN.
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PMID:Differential glycosylation of polymeric and monomeric IgA: a possible role in glomerular inflammation in IgA nephropathy. 1705 Jul 73

The lectin from the legume Vatairea macrocarpa is a galactose/N-acetylgalactosamine binding protein that induced cellular inflammatory response mediated by resident cells. This study investigated which inflammatory mediators would be released from lectin-activated cells. The intraperitoneal injection in rats of the supernatant from cultured macrophages, but not from mast cells, stimulated with lectin induced a time- and dose-dependent release of a neutrophil chemotactic factor, termed MNCF-VML. Pharmacological modulation with dexamethasone inhibited both the lectin-induced chemotactic activity in vivo and also the lectin-induced release of MNCF-VML into the supernatant of cultured macrophages. Cyclooxygenase and lipoxygenase metabolites are apparently not involved in the action of this factor or its release, since indomethacin or MK886 were unable to affect the lectin response. The molecular weight of MNCF-VML was found to be greater than 5 kDa, which led to the investigation of which cytokine(s) could be involved by the following approaches: (a) treatment of animals with antiserum to tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1, or IL-8 before intraperitoneal injection of lectin and (b) addition of antiserum to TNF-alpha, IL-1, or IL-8 to the supernatant of lectin-stimulated macrophages before intraperitoneal administration. Antiserum to TNF-alpha, but not IL-1 nor IL-8, inhibited the neutrophil migration induced either by lectin or MNCF-VML. Our data suggest that neutrophil migration induced by V. macrocarpa lectin occurs via the release of cytokines such as TNF-alpha by macrophages. Thus, this lectin may represent an important tool to better understand pathological situations where an excess of leukocytes at inflammatory sites causes tissue injury.
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PMID:Vatairea macrocarpa (Leguminosae) lectin activates cultured macrophages to release chemotactic mediators. 1717 56

The bacterial single cell protein (BSCP), BioProtein, is dried bacterial mass derived from fermentation of the gram negative bacteria Methylococcus capsulatus, used for animal and fish feed. Workers in this industry suffer frequently from pulmonary and systemic symptoms which may be induced by an inflammatory reaction. The aim of the present study was to examine the effect of BSCP on inflammation in vitro as evaluated by complement activation and cytokine production. Human serum was incubated with BSCP and complement activation products specific for all pathways were detected by enzyme-linked immunosorbent assay (ELISA). Human whole blood anti-coagulated with lepirudin was incubated with BSCP and a panel of 27 biological mediators was measured using multiplex technology. BSCP induced a dose-dependent complement activation as revealed by a pronounced increase in alternative and terminal pathway activation (fivefold and 20-fold, respectively) at doses from 1 microg BSCP/ml serum and a similar, but less extensive (two- to fourfold) increase in activation of the lectin and classical pathways at doses from 100 and 1000 microg BSCP/ml serum, respectively. Similarly, BSCP induced a dose-dependent production of a number of cytokines, chemokines and growth factors in human whole blood. At doses as low as 0 x 05-0 x 5 microg BSCP/ml blood a substantial increase was seen for tumour necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, IL-6, interferon (IFN)-gamma, IL-8, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, IL-4, IL-9, IL-17, IL-1Ra, granulocyte-colony-stimulating factor (G-CSF) and vascular endothelial growth factor (VEGF). Thus, BSCP induced a substantial activation of all three initial complement pathways as well as a pronounced cytokine response in vitro, indicating a potent inflammatory property of this agent.
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PMID:Complement activation and cytokine response by BioProtein, a bacterial single cell protein. 1730 29

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

The anti-cancer activity of mistletoe has been ascribed to a combination of cytotoxic and immunological effects. We previously showed that Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) can stimulate IFN-gamma production and modulate proliferation in murine splenocytes. In this study, we investigated the effects of VCA on human peripheral blood mononuclear cells (hPBMC) and T-lymphocytes. The addition of VCA resulted in a significant inhibition of proliferation at higher concentrations (at 2-8 ng/mL, 1-8 ng/mL in hPBMC and T-lymphocytes, respectively) but an induction at lower concentrations (at 4-16 pg/mL, 4-32 pg/mL in hPBMC and T-lymphocytes, respectively). Further studies were carried out to determine if the pro-proliferative or anti-proliferative activity exhibited by VCA was correlated with apoptosis and cytokine secretion. As a result, the apoptotic cell number increased to 26% after 48 h of VCA treatment (10 ng/mL) in the presence of anti-CD3/CD28 antibodies. On the other hand, without anti-CD3/CD28 antibody stimulants, VCA did not arrest cell cycle. In addition, it was shown that VCA could induce IL-2 secretion was dose-dependently increased by VCA in stimulated (anti-CD3/CD28 antibodies) (at 0.25-2 ng/mL) and non-stimulated (at 3-25 pg/mL) human T-lymphocytes. Also, at low and non-toxic concentrations of VCA, the RT-PCR result confirmed the release of pro-inflammatory cytokines such as IL-1alpha, IL-1beta, IL-6, IL-8, and IFN-gamma. These data may suggest new perspective to modulate the balance between cell growth, cytokine production and programmed cell death therapeutically.
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PMID:Effects of Korean mistletoe lectin (Viscum album coloratum) on proliferation and cytokine expression in human peripheral blood mononuclear cells and T-lymphocytes. 1803 4

Recent in vitro studies have suggested a role for sialylation in chemokine receptor binding to its ligand (Bannert, N., S. Craig, M. Farzan, D. Sogah, N.V. Santo, H. Choe, and J. Sodroski. 2001. J. Exp. Med. 194:1661-1673). This prompted us to investigate chemokine-induced leukocyte adhesion in inflamed cremaster muscle venules of alpha2,3 sialyltransferase (ST3Gal-IV)-deficient mice. We found a marked reduction in leukocyte adhesion to inflamed microvessels upon injection of the CXCR2 ligands CXCL1 (keratinocyte-derived chemokine) or CXCL8 (interleukin 8). In addition, extravasation of ST3Gal-IV(-/-) neutrophils into thioglycollate-pretreated peritoneal cavities was significantly decreased. In vitro assays revealed that CXCL8 binding to isolated ST3Gal-IV(-/-) neutrophils was markedly impaired. Furthermore, CXCL1-mediated adhesion of ST3Gal-IV(-/-) leukocytes at physiological flow conditions, as well as transendothelial migration of ST3Gal-IV(-/-) leukocytes in response to CXCL1, was significantly reduced. In human neutrophils, enzymatic desialylation decreased binding of CXCR2 ligands to the neutrophil surface and diminished neutrophil degranulation in response to these chemokines. In addition, binding of alpha2,3-linked sialic acid-specific Maackia amurensis lectin II to purified CXCR2 from neuraminidase-treated CXCR2-transfected HEK293 cells was markedly impaired. Collectively, we provide substantial evidence that sialylation by ST3Gal-IV significantly contributes to CXCR2-mediated leukocyte adhesion during inflammation in vivo.
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PMID:Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation. 1851 46

The increasing economic importance of fish parasitoses for aquaculture and fisheries has enhanced the interest in the defence mechanisms against these infections. Both innate and adaptive immune responses are mounted by fish to control parasite infections, and several mechanisms described for mammalian parasitoses have also been demonstrated in teleosts. Innate immune initiation relies on the recognition of pathogen-associated molecular patterns (PAMPs) by pathogen recognizing receptors (PRRs). A number of PRRs, mainly Toll-like receptors (TLRs), have been characterized in fish, and some molecules susceptible of functioning as PAMPs are known for some fish parasites. A lectin-carbohydrate interaction has also been described in some host fish-parasite systems, thus probably involving C-type lectin receptors. Inflammatory reactions involving cellular reactions, as phagocytosis and phagocyte activity (including oxidative mechanisms), as well as complement activity, are modulated by many fish parasites, including mainly ciliates, flagellates and myxozoans. Besides complement, a number of humoral immune factors (peroxidases, lysozyme, acute-phase proteins) are also implicated in the response to some parasites. Among adaptive responses, most data deal with the presence of B lymphocytes and the production of specific antibodies (Abs). Although an increasing number of T-cell markers have been described for teleosts, the specific characterization of those involved in their response is far from being obtained. Gene expression studies have demonstrated the involvement of other mediators of the innate and adaptive responses, i.e., cytokines [interleukins (IL-1, IL-8), tumor necrosis factor (TNF), interferon (IFN)], chemokines (CXC, CC), as well as several oxidative enzymes [inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX-2)]. Information is scarcer for factors more directly linked to adaptive responses, such as major histocompatibility (MH) receptors, T cell receptors (TCRs) and IgM. Expression of some immune genes varied according to the phase of infection, and proinflammatory cytokines were mainly activated in the early stages. Gene expression was generally higher in the target tissues for some skin and gill parasites, as Ichthyophthirius multifiliis, Neoparamoeba spp. and Lepeophtheirus salmonis, thus confirming the relevance of mucosal immunity in these infections. The existence of protective responses has been demonstrated for several fish parasites, both in natural infections and in immunization studies. Most information on the mechanisms involved in protection deals with the production of specific Abs. Nevertheless, their levels are not always correlated to protection, and the precise involvement of immune mechanisms in the response is unknown in many cases. No commercial vaccine is currently available for piscine parasitoses, although experimental vaccines have been assayed against I. multifiliis, Cryptobia salmositica and scuticociliates. The known information points to the need for integrated studies of the mechanisms involved in protection, in order to choose the optimum antigen candidates, adjuvants and formulations.
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PMID:Fish immunity and parasite infections: from innate immunity to immunoprophylactic prospects. 1878 35

The macrophage-derived neutrophil chemotactic factor (MNCF) is an alpha-galactoside-binding lectin, known to induce dexamethasone-insensitive neutrophil recruitment. We further characterized MNCF effects on neutrophils and showed that it shares with TNF-alpha the ability to delay apoptosis and to trigger degranulation. MNCF and TNF-alpha effects show similar kinetics and involve Src kinases and MAPKinases dependent pathways. They were, however, clearly distinguished, since the soluble TNF-receptor etanercept prevented TNF but not MNCF effects, while melibiose disaccharide inhibited MNCF but not TNF effects. Absorption of MNCF on detoxi-gel did not alter its properties, precluding an LPS contamination effect. By contrast, galectin-3 required LPS to activate neutrophils. Specific antibodies allowed to further demonstrate that MNCF and galectin-3 are two distinct molecules. Finally, MNCF- and IL-8-induced neutrophil activation differed by their kinetic and sensitivity to pertussis toxin. In conclusion, MNCF is a distinct neutrophil agonist, with pro-inflammatory activities involving its carbohydrate recognition domain.
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PMID:The macrophage-derived neutrophil chemotactic factor, MNCF: a lectin with TNF-alpha-like activities on neutrophils. 1881 67

Staphylococcus epidermidis is an opportunistic biofilm-forming pathogen associated with neurosurgical device-related meningitis. Expression of the polysaccharide intercellular adhesin (PIA) on its surface promotes S. epidermidis biofilm formation. Here we investigated the pro-inflammatory properties of PIA against primary and transformed human astrocytes. PIA induced IL-8 expression in a dose- and/or time-dependent manner from U373 MG cells and primary normal human astrocytes. This effect was inhibited by depletion of N-acetyl-beta-d-glucosamine polymer from the PIA preparation with Lycopersicon esculentum lectin or sodium meta-periodate. Expression of dominant-negative versions of the TLR2 and TLR4 adaptor proteins MyD88 and Mal in U373 MG cells inhibited PIA-induced IL-8 production. Blocking IL-1 had no effect. PIA failed to induce IL-8 production from HEK293 cells stably expressing TLR4. However, in U373 MG cells which express TLR2, neutralization of TLR2 impaired PIA-induced IL-8 production. In addition to IL-8, PIA also induced expression of other cytokines from U373 MG cells including IL-6 and MCP-1. These data implicate PIA as an important immunogenic component of the S. epidermidis biofilm that can regulate pro-inflammatory cytokine production from human astrocytes, in part, via TLR2.
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PMID:Staphylococcus epidermidis polysaccharide intercellular adhesin induces IL-8 expression in human astrocytes via a mechanism involving TLR2. 1901 79


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