UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study we examined the mechanisms by which glomerular mesangial cells ingest apoptotic cells and the mesangial cell response to this event, since there is in vivo evidence that such semiprofessional phagocytes participate in phagocytic clearance of both apoptotic leukocytes and apoptotic resident cells from inflamed glomeruli, thereby promoting resolution of glomerulonephritis. Mesangial cell phagocytosis of apoptotic neutrophils in vitro was not affected by inhibitors of lectin-like receptors, phosphatidylserine receptors, the 61D3 Ag, and beta1 and beta2 integrins, receptors which have been implicated in phagocytosis of apoptotic cells by particular populations of semiprofessional and professional phagocytes. However, the specific inhibitory effects of cationic aminosugars, Arg-Gly-Asp-Ser (RGDS) peptide, and mAbs to phagocyte alpha(v)beta3 vitronectin receptor integrin and "bridging" thrombospondin 1 (TSP1) indicated that mesangial cell phagocytosis of apoptotic cells involved an alpha(v)beta3/TSP mechanism akin to that described for human monocyte-derived macrophages (Mphi) in which Mphi CD36 plays an important role in binding "bridging" TSP1. However, mesangial cells did not express CD36 and there was no evidence for involvement of alternative phagocyte receptors for TSP1, heparan sulfate proteoglycan and sulfatides. Nevertheless, phagocytosis of apoptotic neutrophils by either mesangial cells or Mphi failed to elicit secretion of IL-8 and MCP-1, representatives of each major class of proinflammatory chemotactic cytokines. We conclude that mesangial cell phagocytosis of apoptotic neutrophils involves a novel CD36-independent, alpha(v)beta3/TSP-mediated mechanism that is uncoupled from chemokine secretion, emphasizing the injury-limiting potential of mesangial cell phagocytosis of apoptotic cells.
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PMID:Human glomerular mesangial cell phagocytosis of apoptotic neutrophils: mediation by a novel CD36-independent vitronectin receptor/thrombospondin recognition mechanism that is uncoupled from chemokine secretion. 912 3

Activation of the complement cascade and subsequent assembly of the membrane attack complex (MAC) occur in a number of pathophysiological settings. When formed on the surface of endothelial cells in sublytic concentrations, the MAC can induce a number of proinflammatory activities, including the secretion of soluble mediators (eg, interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1) and the up-regulation of cell surface adhesion molecules. Available data indicate that MAC-induced cell activation may occur through several complex signal transduction pathways, but little is known about the intranuclear mechanisms by which complement-derived products promote the up-regulation of inflammatory mediators. Using purified distal complement proteins (C5-9) to assemble functional MAC on early-passage human umbilical vein endothelial cells (HUVECs), we examined mechanisms of MCP-1 and IL-8 induction. Formation of sublytic concentrations of MAC promoted an increase in nuclear factor (NF)-kappa B DNA binding activity within 60 minutes as determined by serial electrophoretic mobility shift assay. Cytosolic to nuclear translocation of NF-kappa B was confirmed by Western immunoblot and immunocytochemical analyses. Formation of the C5b-8 complex also promoted NF-kappa B translocation but to a lesser degree than observed in HUVECs containing complete MAC. No cytosolic to nuclear translocation of the p65 NF-kappa B subunit was observed in unstimulated HUVECs or in cells incubated with the MAC components devoid of C7. Preincubation of HUVECs with pyrrolidine dithiocarbamate prevented MAC-induced increases in IL-8 and MCP-1 mRNA concentrations and protein secretion. A direct cause and effect linkage between MAC assembly and NF-kappa B activation was established through examination of the pharmacological effect of the peptide SN50 on IL-8 and MCP-1 expression. SN50 is a recently engineered 26-amino-acid peptide that contains a lipophilic cell-membrane-permeable motif and a nuclear localization sequence that specifically competes with the nuclear localization sequence of the NF-kappa B p50 subunit. This study provides direct in vitro evidence that the distal complement system (MAC) can promote proinflammatory endothelial cell activation, specifically, increases in IL-8 and MCP-1 mRNA concentrations and protein secretion, and that cytosolic to nuclear translocation of NF-kappa B is necessary for this response.
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PMID:Sublytic concentrations of the membrane attack complex of complement induce endothelial interleukin-8 and monocyte chemoattractant protein-1 through nuclear factor-kappa B activation. 917 95

Development, peak and healing lesions were induced in the skin of rabbits by topical applications (on different days) of the chemical irritant sulfur mustard (SM). Immediately after the rabbits were euthanized, the intact lesions were excised and organ-cultured for 17 to 20 hours. The culture fluids from early, peak and healing SM lesions all showed high chemotactic activity for both PMN and MN. This finding suggests that the PMN and MN, seen microscopically in tissue sections of the lesions, were entering continuously, even during the healing process. The chemotaxins identified were the eicosanoid LTB4, the chemokine IL-8, and proteases producing the complement fragment C5a. Other studies from our laboratory showed that the number of cells containing IL-1, IL-8, MCP-1, and GRO mRNAs was increased in SM lesions. Chemotactic activity was released by both live and dead (frozen and thawed) cell suspensions of PMN, MN, and fibroblasts, suggesting that these cells were major sources of the chemotaxins produced by the SM lesion explants. Explants of normal skin produced considerable chemotactic activity for MN, but not for PMN. Chemotactic activity for PMN, and the release of LTB4, IL-8 and proteases cleaving C5 to C5a, occurred only in explants infiltrated by leukocytes.
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PMID:Chemotactic factors released in culture by intact developing and healing skin lesions produced in rabbits by the irritant sulfur mustard. 918 66

Chemokines are small proteins that selectively activate and recruit leukocytes to sites of inflammation. Several of them, including the CC chemokines RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and the CXC chemokines IL-8, GRO-alpha, ENA-78 have been identified in rheumatoid synovium, implicating a potential role for these molecules in rheumatoid arthritis. We have investigated the expression patterns of CC chemokine receptors in the joints of mice with collagen-induced arthritis, a model for human rheumatoid arthritis. In addition, we have investigated the incidence and severity of arthritis in mice receiving administration of MetRANTES, a modified chemokine which is a nanomolar antagonist of certain CC chemokine receptors. The mRNA expression pattern of the chemokines and their receptors in the joints of arthritic mice was investigated using reverse transcriptase-PCR and in situ hybridization. An upregulation of the CC chemokine receptors mCCR1, mCCR2; mCCR3 and mCCR5 was found in the joints from arthritic mice, compared to control animals. In addition, injections of MetRANTES reduced the incidence of disease in a dose dependent manner. Furthermore, in MetRANTES-treated mice that did develop arthritis a significantly lower severity of disease was observed compared with control animals. Our data clearly demonstrate a role for CC chemokines and their receptors in inflammatory joint destruction and support the use of chemokine receptor antagonists as potential tools to control inflammatory diseases such as rheumatoid arthritis.
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PMID:Effect of a CC chemokine receptor antagonist on collagen induced arthritis in DBA/1 mice. 923 36

Dendritic cells (DC) are migratory cells that exhibit complex trafficking properties in vivo. The present study was designed to characterize receptor expression and responsiveness to chemoattractants of human DC obtained from PBMC by culture with granulocyte/macrophage-CSF and IL-13. DC expressed appreciable levels of the CCR1, CCR2, and CCR5 receptors for the CC chemokines and the chemokine receptors CXCR1, CXCR2, and CXCR4. DC increased intracellular free calcium and migrated in response to the CC chemokines MCP-3, MCP-4, RANTES, MIP-1alpha, MIP-1beta, and MIP-5/HCC2 and the CXC chemokine SDF-1. In contrast, the CC chemokines MCP-1 and eotaxin had little or no activity in the concentration range tested (up to 1 microg/ml). IL-8 and Gro-beta (CXC) and lymphotactin (C chemokines) were also inactive. DC did not respond to 5-HETE, whereas platelet-activating factor was an active agonist. Selected chemokines active on DC in terms of migration and calcium fluxes were examined for their capacity to modulate endocytosis and Ag presentation. Under conditions in which TNF-alpha was active, MCP-1, MCP-3, MIP-1alpha, and RANTES did not affect these two responses. Thus, among hemopoietic elements, DC respond to a unique set of CC and CXC chemokines, and their responsiveness is restricted to migration with no effect on Ag capture and presentation. Chemokines may play a role in the trafficking of DC under resting or stimulated conditions. Chemokine receptors expressed in DC are likely to underlie HIV infection of this cell type.
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PMID:Receptor expression and responsiveness of human dendritic cells to a defined set of CC and CXC chemokines. 925 66

We have examined in detail the activities of IL-13 on monokine production in vitro and compared its effects with those of IL-10 and IFN-gamma. IL-13 and IL-10 show qualitatively and quantitatively similar activities on cytokine production by monocytes when administered simultaneously with LPS i.e. inhibition of IL-1, IL-6 and TNF-alpha, up-regulation of IL1-ra. However when either LPS and IFN-gamma or fixed S. aureus Cowan (SAC) are used to activate monocytes, IL-10 is a much more potent inhibitor of TNF-alpha production than is IL-13. IL-10 is also an extremely potent inhibitor of IL-12 (p70) production when given with either SAC or LPS, while IL-13 has little effect. Indeed, IL-13 actually increases SAC-induced IL-12 production. When IL-13 is administered prior to the LPS stimulation, its modulation of cytokine production is drastically different. Production of IL-12, MCP-1, TNF-alpha and to a lesser extent IL-6 induced by LPS is now "primed", whereas that of IL-1, IL-8, and IL-10 is still inhibited. IL-10 does not show this "priming" effect, and is a dominant inhibitor of IL-13. The initial IL-13 priming effect is not however due to an inhibition of endogenous IL-10 production; nor is it due to inhibition of PGE2 production. The priming effect of IL-13 on IL-12 production is additive with that of IFN-gamma, and is partly independent of IFN-gamma. The earliest event in IL-13 priming so far noted is an increase in TNF-alpha mRNA production at 1-2 hours. IL-13 priming of IL-12 production can be completely abolished by anti-TNF-alpha antibodies suggesting that IL-13 may be priming via increased TNF-alpha expression, although merely substituting TNF-alpha for IL-13 does not reproduce the priming effect. IL-13 is a thus a more subtle immune regulator than IL-10 or IFN-gamma. When administered with LPS or SAC, it dampens the resulting inflammatory response, though in a more selective way than IL-10. In contrast, when it is added before an inflammatory signal, it primes an immunostimulatory monokine secretion profile resembling that of IFN-gamma, but without the proinflammatory IL-1 component. Early in response to an inflammatory stimulus, IL-13 may thus play an essentially anti-inflammatory role, switching to a primarily immunostimulatory role in the case of an ongoing infection.
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PMID:Interleukin-13 effects on activated monocytes lead to novel cytokine secretion profiles intermediate between those induced by interleukin-10 and by interferon-gamma. 926 68

GRO-alpha, GRO-beta and GRO-gamma are closely related peptides that stimulate growth of tumor cells and activate leukocytes in acute inflammatory reactions. In order to study the biology of GRO peptides in the lungs of experimental animals, we have developed and characterized a sensitive and specific immunoassay for rabbit GRO, and used this assay to measure GRO in rabbit lung fluids and plasma. GRO was cloned from a rabbit cDNA library and expressed in Escherichia coli. Specific goat polyclonal antibodies were used to create an antigen-capture immunoassay. The assay is sensitive to approximately 30 pg/ml GRO and does not crossreact with rabbit IL-8 or MCP-1, or human GRO. The assay accurately measures GRO in rabbit bronchoalveolar lavage fluid, plasma and serum. Rabbit erythrocytes bind little GRO and do not interfere with the detection of GRO in lung fluids. Circulating GRO was detected in the plasma of 4 of 6 pathogen-free rabbits, but the function of circulating GRO in normal animals is uncertain. This immunoassay will facilitate the study of the biology of GRO in rabbits with acute and chronic inflammation in the lungs and other tissues.
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PMID:A sensitive immunoassay to detect the alpha-chemokine GRO in rabbit blood and lung fluids. 929 94

Chemokines secreted by endothelium have been demonstrated to promote leucocyte recruitment to sites of inflammation. In the present study we investigated the effect of the T lymphocyte-secreted cytokine interleukin (IL)-13 on endothelial expression of chemokines. Employing in situ hybridization and enzyme-linked immunosorbent assay (ELISA) techniques we demonstrate that IL-13, which shares many of its activities with IL-4, selectively induces expression of the C-C chemokine monocyte chemoattractant protein (MCP)-1 in human umbilical vein endothelial cells (HUVEC). However, it fails to up-regulate other C-C and C-X-C chemokines potentially inducible in endothelium such as RANTES (regulated on activation, normal T expressed and secreted), gro-alpha, or IL-8. IL-13 dose-dependently induces monocyte chemotactic activity by HUVEC which can be efficiently blocked by neutralizing antisera against MCP-1. In contrast to the synergistic effect of IL-13 and tumour necrosis factor-alpha (TNF-alpha) on endothelial vascular cell adhesion molecule-1 (VCAM-1) surface expression, TNF-alpha-induced secretion of MCP-1 is not augmented by IL-13. Studying the signalling pathway activated by IL-13 it is demonstrated that a neutralizing monoclonal antibody (mAb) to the 140,000 MW component of the IL-4 receptor (IL-4R alpha) inhibits the effect of IL-13. Immunoprecipitation studies reveal that endothelial IL-4R alpha is rapidly tyrosine phosphorylated upon treatment with IL-13 and IL-4. We furthermore show that both cytokines activate the signal transducer and activator of transcription (Stat) protein-6 in endothelial cells. Our data suggest that IL-13 partly utilizes components of the IL-4 receptor signalling pathway for induction of endothelial MCP-1 expression to facilitate recruitment of blood leucocytes.
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PMID:Interleukin-13 selectively induces monocyte chemoattractant protein-1 synthesis and secretion by human endothelial cells. Involvement of IL-4R alpha and Stat6 phosphorylation. 930 36

A growing family of proteins, known as the chemokines, play an important role in the recruitment and activation of inflammatory cells. The purpose of these studies was to characterize the chemokine receptors present on human sodium butyrate differentiated EoL-3 cells (dEoL-3 cells). Using a combination of 3' rapid amplification of cDNA ends and nested polymerase chain reaction, we detected mRNA for CC chemokine receptor (CCR)1, CCR2, CCR3 and low level of CCR5. Radioligand binding studies demonstrated high-affinity saturable binding for both 125I-macrophage inflammatory protein (MIP)-1alpha and 125I-regulated upon activation normal T cell expressed and secreted (RANTES) with Kd values of 1.4 and 7 nM, respectively. Competition binding with chemokines demonstrated exactly the same rank order of potency for displacement of both ligands: MIP-1alpha approximately monocyte chemoattractant protein (MCP)-3 approximately RANTES > MIP-1beta >> MCP-1 >>> IL-8. RANTES, MCP-3 and MIP-1alpha all produced concentration-dependent transient increases in intracellular calcium concentrations in dEoL-3 cells. Desensitization studies indicated that RANTES, MIP-1alpha and MCP-3 interacted at the same receptor, which is identical in characterization to the cloned CCR1. 125I-MCP-1 also demonstrated high-affinity satuable binding to dEoL-3 cells with a Kd value of 0.4 nM. Competition studies showed that MCP-3 was slightly more potent than MCP-1 and MCP-2. MIP-1alpha, MIP-1beta and RANTES were unable to displace 125I-MCP-1. Addition of either MCP-1 or MCP-3 produced a concentration-dependent elevation of intracellular calcium with a maximun response 2-fold higher than that seen with RANTES or MIP-1alpha. Desensitization studies indicated that MCP-1 and MCP-3 function through CCR2 on these cells. Thus binding and functional studies indicate that dEoL-3 cells express functional CCR1 and CCR2 and that these cells may serve as an important system with which to study the regulation and role of these receptors.
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PMID:Characterization of functional chemokine receptors (CCR1 and CCR2) on EoL-3 cells: a model system to examine the role of chemokines in cell function. 933 50

We analysed in mice why the salivary gland extract (SGE-2) from Ornithodoros erraticus and O. moubata induce a protective response with Freund's adjuvants (FAs) in swine while the saliva, in natural conditions, does not. Such protection has been ascribed to the fact that administration of SGE-2 plus FAs permits the recognition of certain salivary components that under natural conditions are not immunogenic. The present findings confirm this hypothesis since in mice, which are unable to recognize the above components, the SGE-2-FAs do not induce any protection. We rule out the possibility that the cause of this could lie in the absence of prostaglandin E2 in the SGE-2 (vs saliva) since it is not present in either fluid. Neither could it be due to a change in antibody isotype since those induced by parasites bites and by the SGE-2-FAs are the same (IgG2a > IgG1 > IgG2b; not IgG3, IgM, IgE). No IgG2a were seen when the SGE-2 were administered alone or with alum or ricin. It is therefore suggested that first responses would be Th1 and the second ones Th2, although no IgE is seen in the latter responses either. The parasites do not require complement to feed; by contrast, they block its activation and skin cellular infiltrates, such as those elicited by IL-8, MCP-1 and C5a, do not affect them, regardless of the presence or not of antitick antibodies.
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PMID:Host immune response evasion strategies in Ornithodoros erraticus and O. moubata and their relationship to the development of an antiargasid vaccine. 934 16

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