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)

The mast cell is one of the major effector cells in inflammatory reactions and can be found in most tissues throughout the body. During inflammation, an increase in the number of mast cells can be seen, e.g., in the intraepithelial cell layer after a provoked allergic reaction. Such accumulation probably requires directed migration of mature mast cells or their precursors. To study the migration of human mast cells we used as a model the human mast cell line, HMC-1, and stem cell factor-dependent (also referred to as mast cell growth factor or Kit ligand) cord blood-derived mast cells. The results show that stem cell factor is a potent chemotactic factor for human mast cells in vitro. The chemotactic response to SCF was found to be dose dependent, reaching a maximum at 50 ng/ml. The activity of SCF could be blocked by anti-SCF Abs. We also tested the effect of different intercrines, i.e., IL-8, MIP-1 alpha, MIP-1 beta, RANTES, and MCAF (also referred to as monocyte chemotactic protein 1), on human mast cell migration. Only RANTES was chemotactic for in vitro-developed mast cells. None of the tested intercrines induced migration of HMC-1 cells. For migration, the mast cells were dependent on binding to an extracellular matrix protein. Thus, coating of the filters with fibronectin was required, whereas collagen or laminin did not promote migration. Adhesion of HMC-1 cells to fibronectin could also be shown in an adhesion assay. In addition, expression of receptors for fibronectin could be detected on the surface of the mast cells. These results show that SCF is not only a growth and differentiation factor for human mast cells in vitro but also a potent chemoattractant for such cells.
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PMID:Stem cell factor is a chemotactic factor for human mast cells. 752 4

Monocyte chemotactic and activating factor (MCAF) is the most potent cytokine that activates basophils to release histamine. The response of human basophils to either simultaneous or sequential addition of the chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, platelet factor (PF)4, connective tissue activating peptide III (CTAP-III), interleukin (IL)-8, and inflammatory protein (IP)-10 on MCAF-induced histamine release was studied. Simultaneous addition of MCAF and any of the chemokines studied evoked an augmented response as measured by histamine release, whereas preincubation of leukocytes or purified basophils (80%) with these chemokines decreased MCAF-induced histamine release in a dose-dependent manner. Histamine release by anti-IgE remained unchanged. When tested at 5 x 10(-9) mol/L, the decrease in histamine release by RANTES was 69.2% +/- 3.5%, by MIP-1 alpha 48.8% +/- 3.1%, by MIP-1 beta 42.9% +/- 3.1%, by PF4 56.5% +/- 2.9%, by IL-8 41.2% +/- 2.2, by CTAP III 27% +/- 4.4%, and by IP-10 15.3% +/- 2.6%. The peak inhibition of histamine release by the chemokines was reached within 10 minutes of preincubation with basophils and remained unchanged thereafter. Washing basophils after preincubation with chemokines abolished the inhibition, with the exception of desensitization by low concentrations of MCAF. With the exclusion of MCAF and RANTES, none of the chemokines (at the concentration range of 5 x 10(-8) to 5 x 10(-11)) induced significant (> 10% above spontaneous) histamine release from basophils. Preincubation of basophils with C5a (5 x 10(-10) mol/L) did not affect histamine release, whereas preincubation with granulocyte-macrophage colony-stimulating factor (10 ng/ml) or IL-5 (10 ng/ml) enhanced MCAF-induced histamine release by 121.8% +/- 10.1% and 108% +/- 10.8%, respectively. We have therefore characterized RANTES, MIP-1 alpha, MIP-1 beta, CTAP III, PF4, IL-8, and IP-10 as inhibitors of MCAF-induced histamine release. Although the results are consistent with receptor blockade, the alpha and beta chemokines appear to interact with separate receptors linked to G proteins; thus, a mechanism of receptor class desensitization is proposed. Interaction of this group of cytokines at the site of allergic inflammation may modulate a function of basophils to initiate, augment, or inhibit histamine release.
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PMID:Chemokines of the alpha, beta-subclass inhibit human basophils' responsiveness to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1. 753 29

Leukemia inhibitory factor (LIF) is a cytokine released at the site of injuries where there is a recruitment of monocytes and polymorphonuclear cells. We analyzed the effect of LIF on human monocytes, which are a major source of chemotactic factors. We showed that supernatants of monocytes treated with LIF (50 ng/mL) for 18 hours had chemotactic activity for neutrophils and monocytes that was neutralized by anti-interleukin-8 (anti-IL-8) and anti-monocyte chemotactic and activating factor (anti-MCAF) neutralizing antibodies. Northern blot analysis showed induction of IL-8 and MCAF RNA in monocytes treated with LIF. Both IL-8 and MCAF mRNA were induced within 3 hours of stimulation. IL-8 and MCAF mRNAs expression peaked at 6 hours and 18 hours, respectively. Interferon-gamma (IFN-gamma), a potent monocyte activator, inhibited IL-8 induction by LIF. On the contrary, IFN-gamma by itself induced MCAF and did not affect the LIF-induced MCAF. These results indicate that LIF released at the site of injury by inducing IL-8 and MCAF can play an important role in recruiting leukocytes and that IFN-gamma can differentially regulate this recruitment.
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PMID:Leukemia inhibitory factor induces interleukin-8 and monocyte chemotactic and activating factor in human monocytes: differential regulation by interferon-gamma. 765 23

We report that polyethylene particles can activate mononuclear cells within the joint to produce the monocyte chemotactic and activating factor (MCAF) and to a lesser degree interleukin 8 (IL-8) as judged by immunohistological staining. Polyethylene particles suspended in hyaluronic acid were injected weekly for 12 weeks into the right knee joint of New Zealand white rabbits. The average size of the particles was 7 (3-12) microns in diameter. The left knee joint was injected with hyaluronic acid as the control. The animals were killed after 13 weeks. On the control side, the synovial membrane was histologically normal, without signs of inflammation. In the knees that were injected with polyethylene particles, histological analysis showed a weak inflammatory response, consisting of mononuclear cells, multi-nucleated giant cells and polyethylene particles. In the vicinity of the particles, the presence of mononuclear cells that were highly positive for MCAF was noted, whereas IL-8 was present in endothelial cells and in the lining layer, but not in cells in the vicinity of polyethylene particles, suggesting that polyethylene particles are able to activate cytokine metabolism in a differentiated way in the synovial monocytes.
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PMID:Polyethylene particles stimulate monocyte chemotactic and activating factor production in synovial mononuclear cells in vivo. An immunohistochemical study in rabbits. 862 84

We have tested the histamine releasing properties and priming abilities of a wide range of recombinant or purified cytokines and growth factors on the basophils of 20 subjects (10 atopic and 10 nonatopic). We found that monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), RANTES, human macrophage inflammatory protein-1 alpha and human inflammatory protein-1 beta, Connective tissue activating peptide III and Neutrophil Activating Peptide-2 (NAP-2) cause histamine release from basophils and are all members of the intercrine/chemokine family. MCAF/MCP-1 was as potent as anti-IgE or C5a and it is clearly the major contributor to histamine releasing factor activity. RANTES was the second major histamine releasing factor among the positive cytokines. Both MCAF/MCP-1 and RANTES are present in conditioned mononuclear cell media and can be separated using Mono Q anion exchange chromatography. We also demonstrated that RANTES has unusual chromatographic properties in spite of its isoelectric point of > 9.0 because it is largely found in peak-2 of the Mono Q column rather than peak-1 in which intercrines such as MCAF/MCP-1, IL-8, and connective tissue activating peptide III are found. All other cytokines and growth factors tested were negative, with the exception of IL-3, which caused histamine release in a subpopulation of subjects, and also primed basophils for release by anti-IgE. Other basophil primers for anti-IgE-dependent histamine release were IL-5, mast cell growth factor (c-kit ligand), and insulin-like growth factor II. Using specific neutralizing antibodies we have shown that MCAF/MCP-1, RANTES, and IL-3 contribute significantly to the activity found in mononuclear cell culture supernatants. Granulocyte-macrophage-CSF, IP-10, I-309, IL-7, IL-8, IL-9, IL-10, IL-11, IgE-binding factor, TNF-alpha, TGF-beta 1, fibroblast growth factor, epidermal growth factor, and endothelial cell growth factor were negative for direct histamine release and as primers of basophils. Our results indicate that cytokines belonging to the intercrine/chemokine family are major constituents of the activity known as "histamine releasing factor" found in MNC supernatants.
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PMID:Characterization of the human basophil response to cytokines, growth factors, and histamine releasing factors of the intercrine/chemokine family. 767 99

Pulmonary fibrosis corresponds to an accumulation of collagens and other proteins of the extracellular matrix in the interstitium and alveoli. Biochemical and cellular mechanisms of pulmonary fibrogenesis remain poorly understood. The cells of the alveolitis (macrophages, lymphocytes and neutrophils) play a key role in producing the factors which regulate the proliferation, chemotactism and secretory activity of the fibroblasts. Amongst these factors the cytokines (interleukins, interferons and growth factors) play a definite but very complex role. Certain cytokines stimulate in vitro the attraction and activation of cells of the alveolitis, as well as the multiplication, migration and secretory activity of fibroblasts. The following cytokines are involved: tumour necrosis factor alpha: (TNF alpha), interleukin 1 (IL-1), interleukin 6 (IL-6) interleukin 8 (IL-8) transforming growth factor beta (TGF beta), platelet derived growth factor (PDGF), insulin like growth factor 1 (IGF-1), fibronectin, monocyte chemotactic protein 1: (MCP-1). Other cytokines, principally the interferons (of alpha, beta or gamma type: IFN alpha, IFN beta, IFN gamma) inhibit in vitro and in vivo the proliferation and the production of collagen by fibroblasts. During the course of human pulmonary fibrosis or in experimental situations, the majority of the cytokines mentioned above are produced in excess in the lung. Without doubt they play an important role in the pathogenesis of fibrosis, even if it is not yet very well known how they interact and contribute in vitro to the process of fibrogenesis. Certain cytokines potentially regulating in the fibrosis are yet to be identified. In the future the use of cytokines and of their inhibitors will perhaps provide new therapies in pulmonary fibrosis.
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PMID:[Cytokines and pulmonary fibroses]. 768 79

Molecules representative of different classes of chemotactic agents, including formyl-Met-Leu-Phe (FMLP), C5a, leukotriene B4, platelet-activating factor, and interleukin (IL)-8, caused a rapid reduction in the IL-1 binding capacity by human polymorphonuclear leukocytes (PMN), a cell type expressing predominantly the IL-1 type II decoy receptor (IL-1 decoy RII). N-t-Boc-Met-Leu-Phe, an antagonist for the FMLP receptor, inhibited the loss of IL-1 binding capacity induced by FMLP. Monocyte chemotactic protein 1, a chemokine related to IL-8 but inactive on PMN, had no effect on IL-1 binding in this cell type. FMLP was selected for further detailed analysis of chemoattractant-induced loss of IL-1 binding by PMN. The action of FMLP was rapid, reaching 50% of its maximum (80%) at 30 s, the earliest measurable time point, and plateauing between 10 and 30 min. Dose-response analysis revealed that maximal reduction of IL-1 binding was reached at FMLP concentrations that were also optimal for chemotaxis (50% effective dose = 5 x 10(-9) M). The loss of IL-1 binding capacity caused by FMLP was determined by a reduction in receptor number with no change in their affinity. The effect of FMLP on IL-1 receptor (IL-1R) was selective in that the PMN surface structures IL-8R, CD16, CD18, and major histocompatibility complex class I antigens were unaffected under these conditions. Loss of surface IL-1R was not due to an augumented rate of internalization. FMLP caused rapid release of a 45-kD IL-1-binding molecule identified as the IL-1 decoy RII. After FMLP-induced release, PMN reexpressed newly synthesized receptors, reaching basal levels by 4 h. FMLP-induced release of the IL-1 decoy RII did not impair the responsiveness of PMN to IL-1 in terms of promotion of survival and cytokine production. FMLP-induced release of the IL-1 decoy RII was unaffected by protein synthesis inhibitors, was blocked by certain protease inhibitors, and was mimicked by agents (the Ca++ ionophore A23187 and phorbol myristate acetate) that recapitulate elements in the signal transduction pathway of chemoattractant receptors. The time frame and concentration range of chemoattractant-induced rapid release of the IL-1 decoy RII are consistent with the view that IL-1 decoy RII release is an early event in the multistep process of leukocyte recruitment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chemoattractants induce rapid release of the interleukin 1 type II decoy receptor in human polymorphonuclear cells. 776 5

The chemokine monocyte chemotactic protein 1 (MCP-1) is a cytokine with chemotactic activity specific for mononuclear phagocytes. To investigate the possible involvement of MCP-1 in the pathogenesis of sepsis, its course was studied in baboons challenged intravenously with a sublethal or lethal dose of Escherichia coli. Levels of MCP-1 started to increase in both groups of animals 2 h after injection of E. coli, reaching peak levels 4 and 6 h after a sublethal (186 +/- 21 ng/mL) or a lethal (213 +/- 24 ng/mL) dose, respectively. Levels of MCP-1 correlated significantly with plasma levels of another chemokine, interleukin-8 (IL-8; r = .826. P < .001), suggesting that common stimuli mediate the release of both cytokines in this model.
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PMID:Monocyte chemotactic protein 1 is released during lethal and sublethal bacteremia in baboons. 776 8

The subendothelial basement membrane (BM) is regarded as an important barrier to the entry of leucocytes into inflammatory sites. This study compares the ability of leucocytes, platelets and endothelial cells (EC) to degrade a [35SO4]-labelled subendothelial extracellular matrix (ECM) and assesses the effect of PMA and various pro-inflammatory cytokines on this degradative activity. The different products of degradation, identified by fast protein liquid chromatography (FPLC) gel filtration chromatography, were indicative of protease, endoglycosidase (heparanase) and exoglycosidase and/or sulfatase activity. In terms of ECM degradation, EC and platelets were the most active, with PMA stimulation further enhancing the degradative activity of these two cell types. Platelets exhibited predominantly heparanase activity whereas the EC degradation products suggested a range of enzymic activities, namely proteases, heparanases and sulfatases. Interestingly, EC in suspension expressed these three enzymic activities whereas confluent EC monolayers only exhibited sulfatase activity, suggesting that the former situation might represent an angiogenic response. In the case of leucocytes, neutrophils and lymphocytes degraded the ECM to a much greater extent than monocytes. Each cell type also differed in the predominant enzymic activities it expressed, for example, heparanase activity by lymphocytes, protease activity by neutrophils and sulfatase activity by monocytes. Furthermore, PMA stimulation was shown to have differential effects on these enzymic activities. Some pro-inflammatory cytokines were found to be cell-type specific in their effects on ECM degradation. Thus, IL-1 + TNF enhanced neutrophil and EC degradation of the ECM but inhibited lymphocyte ECM degradation. In contrast, the chemokine IL-8 enhanced ECM degradation by neutrophils, lymphocytes and EC. Of particular interest was the unique sulfatase activity expressed by EC and monocytes which was induced in EC by TNF + IL-1 and IL-8, whereas in monocytes the sulfatase activity was exclusively induced by the chemokine monocyte chemotactic and activating factor (MCAF). Collectively, the results of this study show that leucocytes differ markedly in the enzymes they express to degrade the BM during extravasation and that PMA and cytokines are cell-type specific in their induction of hydrolytic enzyme activity. These results also indicate that EC may play an important role, not only in the recruitment of leucocytes, but also via sulfatase activity in the preparation of vascular BM for leucocyte extravasion.
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PMID:Comparative analysis of the ability of leucocytes, endothelial cells and platelets to degrade the subendothelial basement membrane: evidence for cytokine dependence and detection of a novel sulfatase. 779 31

This thesis discusses the phenotypic characteristics of different inflammatory dermatological diseases and sets this into context with the specific chemotactic ability of different cytokines. It further discusses the biological properties of different chemotactic cytokines and their relevance in certain inflammatory diseases. The term chemotaxis was introduced in 1884 by Pfeffer, who described it as directional migration of leukocytes along a gradient. Regular studies of chemotaxis were, however, not possible until 1962 when Boyden developed the chemotaxis chamber technique. This test has since then been improved, and it is now possible to define and characterize chemoattractants and examine the special chemotactic behavior of leukocytes. We investigated T lymphocyte responses towards different chemoattractants using a modified Boyden chamber technique and found that approximately 50% of normal individuals have cells which respond whereas T-cells from the remaining persons did not respond. We therefore chose human T lymphocytic cell lines as target cells for chemotaxis screening to avoid inter-individual variations among donors. T lymphocytic infiltrates dominated by CD4+, CD45R0+ memory T cells are characteristic for many dermatological inflammatory diseases. We have therefore performed experiments to evaluate whether an earlier described epidermal lymphocyte chemotactic factor (ELCF) from skin overlying a tuberculin skin reaction in addition with other cytokines specifically attracts different subsets of lymphocytes. ELCF which probably reflects a mixture of different epidermal T lymphocyte chemotactic factors rather than a single factor was shown to specifically attract CD4+, CD45R0+ T lymphocytes in contrast to fMLP, IL-8, C5a and LTB4, which induced equal chemotaxis for both CD4+ and CD8+ T lymphocytes. A newly described inhibitory cytokine IL-10 selectively attracted the CD8+ subpopulation of T lymphocytes, and it is suggested that IL-10 could be an important factor in the downregulation of an inflammatory response. The recently discovered neutrophil chemotactic and activating factor IL-8 has been shown to be chemotactic for T lymphocytes as well. It belongs to a family of 8,000-10,000 KDa peptides of which a monocyte chemotactic and activating factor MCAF is also a member. We showed that mRNA for IL-8 could be expressed in highly purified T lymphocytes only upon stimulation with ionomycin and PHA or PMA and PHA, and to a lesser extent PMA and IL-2. This is consistent with other reports of T lymphocytes requiring two signals for cytokine production. We showed that it was only the CD4+ subpopulation of the T lymphocytes that expressed IL-8 mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chemotactic cytokines and inflammation. Biological properties of the lymphocyte and monocyte chemotactic factors ELCF, MCAF and IL-8. 790 57

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