Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

KM+, a lectin purified from Artocarpusintegrifolia seeds, is an attractant for neutrophils, and has properties similar to fMLP, IL-8 and MNCF. The endogenous lectin MNCF, inhibits carrageenan-induced neutrophil migration when intravenously administered in rats. In an attempt to mimic the activity of MNCF with KM+, we determined the effect of intravenous (iv) injection of KM+ (5 microg) on neutrophil migration to the peritoneal cavity of Wistar rats induced by KM+ (50 microg, intraperitoneal, ip), fMLP (5 ng, ip) and carrageenan (300 microg, ip). Initially we evaluated the effect of the time interval between intravenous and intraperitoneal administration of KM+. The intervals ranged from 20 to 120 min and progressively stronger inhibition was observed with increasing time intervals up to a maximum of 60 min, with effect decreasing thereafter. With injections at the optimum interval of 60 min, we observed that KM+ inhibited KM+- and carrageenan-induced neutrophil migration by 72%, and fMLP-induced migration by 56%. White cell counts for Wistar rats that only received KM+iv, performed at 0 to 120 min intervals after injection, revealed early neutropenia lasting 60 min, followed by a marked increase in circulating neutrophils that reached a maximum of twice the initial levels within 90 min and after 120 min returned to levels near to that observed before intravenous administration of KM+. These results indicate that when KM+ is present in the intravascular space, it produces an inhibitory effect on neutrophil migration similar to that caused by the intravenous administration of other chemoattractants, regardless of whether they act through a mechanism independent of carbohydrate recognition, as does IL-8, or are dependent on carbohydrate recognition, like MNCF.
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PMID:An intravascular chemoattractant lectin inhibits neutrophil migration. 988 57

We studied the large-scale production of a variety of natural cytokines during the activation and expansion of human T lymphocytes in a hollow fiber bioreactor culture system. Peripheral blood mononuclear cells (PBMC) were activated using phytohemagglutinin plus recombinant interleukin-2 (IL-2). Phytohemagglutinin was either present in the hollow fiber bioreactor during the entire 15-16-day culture period or only during the 20-h preactivation of the PBMC in culture bags. The expanding T lymphocytes were mainly CD3+,8+ and exerted maximal natural, activated, bispecific monoclonal antibody-redirected and lectin-dependent cytolytic activities between days 9 and 13 of culture. IL-1 and IL-4 were only produced in low amounts. IL-8 and lymphotoxin were primarily produced during the first week of culture. Harvest of the hollow fiber bioreactor culture supernatant at the time of peak cytokine concentration would have yielded per 10(8) PBMC input between 3.7 and 4.9 micrograms of IL-8 (at days 2 or 3), and between 0.02 and 0.5 microgram of lymphotoxin (at days 6 or 7). Tumor necrosis factor-alpha and IL-6 were produced during the entire culture period of 15 or 16 days: per 10(8) PBMC input, between 0.1 and 0.4 microgram of tumor necrosis factor-alpha (at days 2 or 3) and between 0.03 and 0.5 microgram of IL-6 (at days 15 or 16). Production of interferon-gamma and granulocyte-macrophage colony-stimulating factor started from initiation of cultures onwards to reach peak levels at the end of the 15- or 16-day culture period, yielding at that time between 2.1 and 17.7 micrograms/ml of interferon-gamma and between 0.4 and 4.2 micrograms of granulocyte-macrophage colony-stimulating factor per 10(8) PBMC input. The production of tumor necrosis factor-alpha, IL-6, interferon-gamma, and granulocyte-macrophage colony-stimulating factor was proportional to the extent of lymphocyte multiplication. These results demonstrate the usefulness of hollow fiber bioreactor cultures to produce natural cytokines during the activation and expansion of predominantly CD3+,8+ T lymphocytes.
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PMID:Large-scale production of natural cytokines during activation and expansion of human T lymphocytes in hollow fiber bioreactor cultures. 1040 31

Cultured Caco-2 cells were stimulated with Lens culinaris, Phaseolus vulgarisandVicia fabalectins. The production of IL-1, IL-6, IL-8 and MCP-1 was measured by ELISA and RT-PCR. IL-8 production appeared to be specifically triggered upon stimulation with all three lectins used, since none of the other cytokines tested were produced. The IL-8 secreted may induce the extravasation of activated neutrophils and generate tissue damage. A similar mechanism may be implicated in the lesions observed after infection by some enteric pathogens, with lectin-like domains on their membrane. Finally, this model may be suitable one to study the regulation of IL-8 production.
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PMID:Lens culinaris, Phaseolus vulgaris and vicia faba lectins specifically trigger IL-8 production by the human colon carcinoma cell line CACO-2. 1093 Mar 14

Microglia are a major glial component of the central nervous system (CNS), play a critical role as resident immunocompetent and phagocytic cells in the CNS, and serve as scavenger cells in the event of infection, inflammation, trauma, ischemia, and neurodegeneration in the CNS. Studies of human microglia have been hampered by the difficulty of obtaining sufficient numbers of human microglia. One way to circumvent this difficulty is to establish permanent cell lines of human microglia. In the present study we report the generation of immortalized human microglial cell line, HMO6, from human embryonic telencephalon tissue using a retroviral vector encoding myc oncogene. The HMO6 cells exhibited cell type-specific antigens for microglia-macrophage lineage cells including CD11b (Mac-1), CD68, CD86 (B7-2), HLA-ABC, HLA-DR, and ricinus communis agglutinin lectin-1 (RCA), and actively phagocytosed latex beads. In addition, HMO6 cells showed ATP-induced responses similar to human primary microglia in Ca2+ influx spectroscopy. Both human primary microglia and HMO6 cells showed the similar cytokine gene expression in IL-1beta, IL-6, IL-8, IL-10, IL-12, IL-15, and TNF-alpha. Using HMO6 cells, we investigated whether activation was induced by Amyloid-beta fragments or lipopolysaccharide (LPS). Treatment of HMO6 cells with Amyloid-beta 25-35 fragment (Abeta(25-35)) or Amyloid-beta 1-42 fragment (Abeta(1-42)) led to increased expression of mRNA levels of cytokine/chemokine IL-8, IL-10, IL-12, MIP-1beta MIP-1, and MCP-1, and treatment with LPS produced same results. Expression of TNF-alpha and MIP1-alpha was not detected in unstimulated HMO6 cells, but their expression was later induced by long-term exposure to Abeta(25-35) or Abeta(1-42.) ELISA assays of spent culture media showed increased protein levels of TNF-alpha and IL-8 in HMO6 cells following treatment with Abeta(25-35) or LPS. Taken together, our results demonstrate that treatment of human primary microglia and HMO6 immortalized human microglia cell line with Abeta(25-35), Abeta(1-42) and LPS upregulate gene expression and protein production of proinflammatory cytokines and chemokines in these cells. The human microglial cell line HMO6 exhibits similar properties to those documented in human microglia and should have considerable utility as an in vitro model for the studies of human microglia in health and disease.
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PMID:Generation and characterization of immortalized human microglial cell lines: expression of cytokines and chemokines. 1174 1

Enriched populations of human microglial cells were isolated from mixed cell cultures prepared from embryonic human telencephalon tissues. Human microglial cells exhibited cell type-specific antigens for macrophage-microglia lineage cells including CD11b (Mac-1), CD68, B7-2 (CD86), HLA-ABC, HLA-DR and ricinus communis aggulutinin lectin-1 (RCA-1), and actively phagocytosed latex beads. Gene expression and protein production of cytokines, chemokines and cytokine/chemokine receptors were investigated in the purified populations of human microglia. Normal unstimulated human microglia expressed constitutively mRNA transcripts for interleukin- 1beta (IL-1beta) -6, -8, -10, -12, -15, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and monocyte chemoattractant protein-1 (MCP-1), while treatment with lipopolysaccharide (LPS) or amyloid beta peptides (Abeta) led to increased expression of mRNA levels of IL-8, IL-10, IL-12, TNF-alpha, MIP-1alpha, MIP-1beta, and MCP-1. Human microglia, in addition, expressed mRNA transcripts for IL-1RI, IL-1RII, IL-5R, IL-6R, IL-8R, IL-9R, IL-10R, IL-12R, IL-13R, and IL-15R. Enzyme-linked immunosorbent assays (ELISA) showed increased protein levels in culture media of IL-1beta, IL-8, TNF-alpha, and MIP-1alpha in human microglia following treatment with LPS or Abeta. Increased TNF-alpha release from human microglia following LPS treatment was completely inhibited with IL-10 pretreatment, but not with IL-6, IL-9, IL-12, IL-13, or transforming growth factor-beta (TGF-beta). Present results should help in understanding the basic microglial biology, but also the pathophysiology of activated microglia in neurological diseases such as Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, stroke, and neurotrauma.
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PMID:Cytokines, chemokines, and cytokine receptors in human microglia. 1211 20

When injected subcutaneously, extracts from the white berry mistletoe (Viscum album L) lead to a dose-dependent local inflammatory reaction at the injection site. From in vitro investigations with V album extracts, the release of proinflammatory cytokines from peripheral blood mononuclear cells and from a human skin model (Skin(2) model; Advanced Tissue Sciences, La Jolla, CA) is known. This shows dose dependence for mistletoe lectin-I in the range of 0.02 ng/mL to 10.0 ng/mL. In this study, an investigation was conducted of which cytokines are released in the skin by the mistletoe lectin-standardized mistletoe extracts Viscum album QuFrF (VaQuFrF) and Iscador Qu Spzial (IQuS) (Institute Hiscia, Arlesheim, Switzerland) and whether dose dependency exists. The model used for this study is the multilayered skin model EpiDerm (MatTek Corporation, Ashland, MA), which consists of multilayered keratinocytes. The viability of the cell culture was measured after incubation with 0.01, 0.1, 0.2, 0.3, 0.5, and 15.0 ng/mL VaQuFrF or 0.01, 0.1, 0.2, 0.3, 0.5, 5.0, and 15.0 ng/mL IQuS. The release of interleukin (IL)-1alpha, IL-2, IL-6, IL-8, IL-10, IL-12p(40+70), IL-12p(70), tumor necrosis factor-alpha (TNFalpha), interferon (IFN)-alpha, IFNgamma, granulocyte macrophage-colony stimulating factor, and RANTES was determined after incubation with 0.5 ng/mL of IQuS ng/mL and VaQuFrF. The dose dependency of the release of IL-1alpha and IL-6 after incubation with 0.5 and 15.0 ng/mL VaQuFrF or 0.5 ng/mL, 5.0 ng/mL, and 15.0 ng/mL IQuS and that of the release of IL-1alpha, IL-2, IL-6, IL-10, and TNFalpha after incubation with 0.01 ng/mL, 0.1 ng/mL, 0.2 ng/mL, 0.3 ng/mL, and 0.5 ng/mL VaQuFrF or IQuS were determined. A dose-dependent decrease of cellular viability and an increase of IL-1alpha, IL-6, and TNFalpha as well as the release of IL-8 could be demonstrated. These results are compatible with the hypothesis that the subcutaneous injection of VaQuFrF and IQuS leads to a release of proinflammatory cytokines at the injection site.
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PMID:Cytokine release of a keratinocyte model after incubation with two different Viscum album L extracts. 1252 19

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that are characterized by chronic intestinal inflammation and a constant influx of leukocytes mediated by pro-inflammatory cytokines and chemokines. The intestinal expression of the CXCR1-binding chemokines IL-8/CXCL8 and GCP-2/CXCL6 and the participation of immunocompetent cells in IBD were evaluated. IL-8 production by peripheral blood mononuclear cells (PBMC) from IBD patients, stimulated with endotoxin, plant lectin or double-stranded RNA, was significantly lowered in patients with CD, but not in UC patients or healthy subjects. The reduced chemokine production by PBMC from IBD patients was both IL-8 and CD specific, but not inducer dependent. In serum, most chemokines remained undetectable, while the levels of those that were measurable remained unaltered in IBD patients. GCP-2, but not ENA-78/CXCL5, nor IL-8, were highly expressed by endothelial cells in inflamed intestinal tissue of IBD patients. In contrast, stimulated endothelial cell cultures produced more IL-8 than GCP-2. The selective GCP-2 staining of endothelial cells at sites of ulcerations suggests that GCP-2, despite its low production capacity in vitro, plays a role in IBD that is different from that of structurally (ENA-78) and functionally (IL-8) related ELR(+) CXC chemokines. Thus, the chemokine network shows complementarity rather than redundancy.
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PMID:CXCR1-binding chemokines in inflammatory bowel diseases: down-regulated IL-8/CXCL8 production by leukocytes in Crohn's disease and selective GCP-2/CXCL6 expression in inflamed intestinal tissue. 1521 47

Viscum album agglutinin-I (VAA-I) is a plant lectin which possesses antitumoral properties. This lectin is also known for its immunostimulatory effects when used at low concentrations (1-100 ng/ml). We have demonstrated recently that VAA-I is a potent inducer of human neutrophil apoptosis in vitro when used at higher concentrations. The role of VAA-I on activated neutrophils has not so far been investigated and its potential proinflammatory properties in vivo are poorly documented. Herein, we demonstrated that VAA-I (1000 ng/ml) induces apoptosis in lipopolysaccharide (LPS)-treated human neutrophils in vitro as well as in murine neutrophils isolated from lipopolysaccharide (LPS)-induced neutrophil influx. Using this model, we found that administration of VAA-I (100 or 1000 ng/ml) did not induce an inflammatory response. However, when used at 1 or 10 ng/ml, VAA-I was found to significantly induce a transitory inflammatory response, based on an increased leucocyte infiltration (>98% neutrophils). Also, we found that VAA-I inhibits LPS-induced neutrophil influx when administered simultaneously with LPS. In such conditions, some characteristic apoptotic neutrophils were observed in the pouch. Unlike LPS, which increased the production of some cytokines, VAA-I (1 or 10 ng/ml) did not increase the production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1Ra, IL-1alpha, IL-beta, IL-8, IL-10 or IL-12 (p70) in human neutrophils. We conclude that VAA-I possesses the ability to induce apoptosis of preactivated neutrophils at a concentration that does not induce a proinflammatory response. Moreover, we conclude that VAA-I can inhibit a LPS-induced proinflammatory response in vivo. These data may provide new clinical perspectives in future mistletoe therapy and favour its potential utilization based on anti-inflammatory activity that at first appears contradictory with its use as immunostimulant.
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PMID:Anti-inflammatory effect of Viscum album agglutinin-I (VAA-I): induction of apoptosis in activated neutrophils and inhibition of lipopolysaccharide-induced neutrophilic inflammation in vivo. 1527 Aug 43

Human CD33 is a myeloid-restricted transmembrane protein of the sialic acid-binding Ig-like lectin (Siglec) family. While structural analysis predicts an inhibitory function, it remains unknown under which circumstances CD33 may operate as an inhibitory molecule. Here we show that treatment of human monocytes with anti-CD33 mAb induces the production of the proinflammatory cytokines IL-1 beta, TNF-alpha, and IL-8. However, decreased CD33 surface expression obtained by RNA interference using cognate small interfering RNA (siRNA) was specifically paralleled by spontaneous cytokine production. Similarly, sialic acid (CD33 ligand) removal from the monocyte surface by neuraminidase resulted in IL-1 beta up-regulation, while the addition of red blood cells or sialyllactosamine (but not lactosamine) reversed the effect of neuraminidase treatment, thus demonstrating the importance of ligand recognition by CD33 for repression of monocyte activation. Finally, inhibition of phosphoinositide 3-kinase (PI3K) dramatically enhanced the IL-1 beta response to anti-CD33 and neuraminidase, while inhibition of p38 mitogen-activated protein kinase (MAPK) abolished it. Simultaneous addition of both inhibitors resulted in low levels of IL-1 beta, suggesting that CD33 exerts an inhibitory role mediated by PI3K, while p38 MAPK signaling is required for IL-1 beta production. These data indicate that by controlling monocyte activation, CD33 is a key molecule in the inflammatory response, depending on the sialic acid microenvironment for its repressor activity.
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PMID:Constitutive repressor activity of CD33 on human monocytes requires sialic acid recognition and phosphoinositide 3-kinase-mediated intracellular signaling. 1559 23

Decorin and biglycan are closely related abundant extracellular matrix proteoglycans that have been shown to bind to C1q. Given the overall structural similarities between C1q and mannose-binding lectin (MBL), the two key recognition molecules of the classical and the lectin complement pathways, respectively, we have examined functional consequences of the interaction of C1q and MBL with decorin and biglycan. Recombinant forms of human decorin and biglycan bound C1q via both collagen and globular domains and inhibited the classical pathway. Decorin also bound C1 without activating complement. Furthermore, decorin and biglycan bound efficiently to MBL, but only biglycan could inhibit activation of the lectin pathway. Other members of the collectin family, including human surfactant protein D, bovine collectin-43, and conglutinin also showed binding to decorin and biglycan. Decorin and biglycan strongly inhibited C1q binding to human endothelial cells and U937 cells, and biglycan suppressed C1q-induced MCP-1 and IL-8 production by human endothelial cells. In conclusion, decorin and biglycan act as inhibitors of activation of the complement cascade, cellular interactions, and proinflammatory cytokine production mediated by C1q. These two proteoglycans are likely to down-regulate proinflammatory effects mediated by C1q, and possibly also the collectins, at the tissue level.
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PMID:Interactions of the extracellular matrix proteoglycans decorin and biglycan with C1q and collectins. 1617 19


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