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)

Previously, we identified peptides that stimulate phosphoinositide hydrolysis in several leukocyte cell lines from mixtures of random hexapeptide sequences. Moreover, the peptides activate phospholipase C via a pertussis toxin-sensitive G protein-coupled receptor. We now investigate the structure-activity relationship of the peptides with the goal of improving the activity of the peptides, as well as the biologic function of the peptides. Substitution of the L-methionine at the C terminus of peptides with D-methionine markedly increased the effectiveness of the peptides. The half-maximal effective concentrations of MKYMPm-NH2 and WKYMVm-NH2 for stimulation of phosphoinositide hydrolysis in U266 cells were 30 and 0.5 nM, respectively. By BIAcore analysis we confirmed the existence of a receptor for WKYMVm-NH2. Furthermore, the intracellular calcium concentration increase induced by WKYMVm-NH2 was not inhibited by several chemoattractants (FMLP, IL-8, platelet-activating factor, C5a, granulocyte-macrophage CSF, and granulocyte CSF) suggests that WKYMVm-NH2 has a unique cell surface receptor on leukocytes. WKYMVm-NH2 stimulated the phosphoinositide hydrolysis in U937, HL60, and U266 cells, as well as in human neutrophils. Moreover, WKYMVm-NH2 is more effective than FMLP in the production of superoxide in human neutrophils. The data suggest that WKYMVm-NH2 may have the ability to activate the microbicidal functions of human neutrophils.
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PMID:A peptide with unique receptor specificity: stimulation of phosphoinositide hydrolysis and induction of superoxide generation in human neutrophils. 902 31

To investigate the responses of dendritic cells (DC) during Gram-negative infections, we analyzed the effects of graded doses of LPS on the cytokine profile, phenotype, and allostimulatory potential of human DC generated by culturing plastic-adherent PBMC in presence of IL-4 and granulocyte-macrophage-CSF. First, we found that LPS stimulates the production of high levels of TNF-alpha, IL-6, IL-8, IL-12 by DC and up-regulates their expression of HLA-DR, B7-1, B7-2, and CD40. The effects of LPS were dose dependent, with a significant stimulatory effect already observed at a concentration of 0.1 ng/ml and a plateau being reached at 10 ng/ml. These phenotypic changes correlated with increased allostimulatory properties of LPS-activated DC because DC treated with LPS were significantly more efficient than untreated DC in eliciting IL-2 and IFN-gamma synthesis by alloreactive T cells and stimulating their proliferation. Experiments using neutralizing anti-IL-12 mAb indicated that LPS-induced IL-12 is responsible for the increased production of IFN-gamma but not for the increased proliferation during MLR. Finally, we observed that the DC responses to low levels of LPS (1 ng/ml) were dramatically inhibited by a blocking anti-CD14 mAb, although DC do not express CD14 molecules on their membrane. Experiments using serum depleted of soluble CD14 (sCD14) and sCD14 either purified from human serum or in recombinant form further established that DC respond to LPS via a soluble CD14-dependent pathway.
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PMID:Bacterial lipopolysaccharide stimulates the production of cytokines and the expression of costimulatory molecules by human peripheral blood dendritic cells: evidence for a soluble CD14-dependent pathway. 905 30

Cytokines play an important role in granuloma formation, but the extent that cytokine profiles are similar in different granulomatous diseases and whether differences in the histopathologic features of the granulomatous response results from differences in cytokine production have not been evaluated. To investigate these questions, we used RT-PCR to quantify the expression of mRNAs coding for 16 cytokines in granulomatous lymph nodes from patients with tuberculosis and sarcoidosis and from control tissues, and we sought correlations between the level of expression of these cytokines and the histopathologic features of the granulomas. Expression of mRNAs coding for a number of cytokines (IL-1beta, IFN-gamma, TNF-alpha, granulocyte-macrophage (GM)-CSF, IL-12 (p40), and lymphotoxin-beta) was increased in tuberculous and sarcoid granulomas compared with that of control tissues. All sarcoid granulomas were shown to express a Th1 pattern of cytokine mRNAs, while tuberculous lymph nodes expressed either a Th1 or a Th0 profile. GM-CSF and lymphotoxin-beta mRNAs were more abundant in sarcoid than in tuberculous granulomas, whereas IL-8 mRNA was strongly expressed only in tuberculous lymph nodes. Strong expression of GM-CSF, TNF-alpha, and IL-8 by granulomas was shown to be correlated, respectively, with the presence of florid granulomatous lesions, the absence of central necrosis, and the presence of neutrophil infiltration. These results demonstrate that the formation of tuberculous and sarcoid granulomas in humans is associated with the expression of characteristic cytokine profiles and indicate that the expression of certain cytokines is associated with the development of specific pathologic features in the resulting granulomas.
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PMID:Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response. 930 Jul 29

The conditions that control the migratory status of hematopoietic progenitor cells on extracellular matrix (ECM) and that decide whether a cell migrates or adheres are incompletely understood. We analyzed the migratory behavior of murine hematopoietic progenitor cells factor-dependent-cell-paterson (FDCP)-mix and purified lin-Sca1+ bone marrow cells on ECM. We found that migration on fibronectin (Fn) or laminin (Lam) becomes dependent on beta1-integrins if a surface restraint force is introduced by tilting the ECM-coated culture vessels. Under these conditions, migration specifically occured on Fn and Lam, and was not detected on collagen IV-, hyaluronate-, or bovine serum albumin- coated surfaces. Migration depended on the continuous presence of hematopoietic cytokines interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage-CSF (M-CSF), granulocyte-macrophage-CSF (GM-CSF), or stem cell factor (SCF), whereas other cytokines, such as IL-8, macrophage inflammatory protein-1alpha, macrophage-chemotactic and activating factor, and erythropoietin resulted in very little or no migratory response. IL-3 induced migration was synergistically enhanced by other CSFs, but was completely inhibited by addition of transforming growth factor-beta1. In contrast to firm local adhesion of previously cytokine depleted progenitors that was rapidly inducible within 1 hour after exposure to cytokines, preincubation on Fn matrix for 4 to 6 hours was required before cytokines could induce migration. A sudden increase of cytokine concentration reversibly inhibited migration and induced a fully adhesive state; this effect could be prolonged by consecutive stimulation with heterologous cytokines. Whereas cytokines activated resting progenitor cells to migrate on ECM, cell migration speed was regulated by Fn concentration. These results indicate that beta1-integrin-mediated progenitor cell adhesion and migration are differentially regulated by external stimuli and suggest that this regulation corresponds to different activation states of beta1-integrins in hematopoietic progenitor cells.
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PMID:Adhesion and migration are differentially regulated in hematopoietic progenitor cells by cytokines and extracellular matrix. 934 36

Treatment of primary monocytes with soluble HIV-Tat protein is associated with increased monocyte metalloproteinase-9 (MMP-9) expression and enhanced beta 2 integrin expression that increases monocyte/endothelial adhesion. These alterations require greater than 12 h of HIV-Tat treatment, suggesting the involvement of intermediate factors. Thus, we have examined the role of cytokines in the HIV-Tat-induced alteration of monocyte function. Treatment of monocytes with HIV-Tat rapidly up-regulated the production of IL-1 beta, IL-6, IL-8, and TNF-alpha, but not IL-3, granulocyte-macrophage CSF, basic fibroblast growth factor, or macrophage-inflammatory protein-1 alpha, and was associated with up-regulation of the corresponding cytokine mRNA. Inclusion of neutralizing anti-cytokine Abs to IL-1 beta or TNF-alpha during the HIV-Tat pretreatment period significantly inhibited the HIV-Tat-induced increase in MMP-9 production, monocyte/endothelial adhesion, and monocyte-dependent endothelial damage. In contrast, neutralizing Abs against IL-6 and IL-8 had no effect. The effects of HIV-Tat treatment, namely MMP-9 production, enhanced monocyte/endothelial cell adhesion, and monocyte-dependent endothelial damage, were mimicked by treating the monocytes with IL-1 beta or TNF-alpha, but not with IL-6 or IL-8. Therefore, the mechanism by which HIV-Tat activates monocyte function is dependent on HIV-Tat-induced production of cytokines (IL-1 beta and TNF-alpha).
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PMID:Activation of monocytes by HIV-Tat treatment is mediated by cytokine expression. 937 98

The human bladder carcinoma cell line KU-19-19 synthesizes and secretes hematopoietic growth factors. Conditioned medium (CM) from KU-19-19 stimulated the [3H]thymidine incorporation of growth factor-dependent hematopoietic cell lines. ELISA documented high amounts of granulocyte colony-stimulating factor (G-CSF; > 5 ng/ml); also granulocyte-macrophage CSF (GM-CSF), macrophage-CSF (M-CSF), stem cell factor (SCF), IL-6, and IL-8 were detected in KU-19-19 CM. Pretreatment with phorbol ester, IL-1 beta, or IFN-gamma increased the level of G-CSF, GM-CSF, and M-CSF in KU-19-19 CM. Thus, KU-19-19 represents a reliable source for purification of G-CSF and can easily be used to support proliferation of growth factor-dependent cell lines. The ability to respond to different stimuli suggests that several regulatory pathways may be involved in cytokine production of this bladder carcinoma cell line.
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PMID:Bladder carcinoma cell line KU-19-19-derived cytokines support proliferation of growth factor-dependent hematopoietic cell lines: modulation by phorbol ester, interferon-gamma and interleukin-1 beta. 946 44

Mitogen-activated protein (MAP) kinase-mediated signal-transduction pathways convert extracellular stimulation into a variety of cellular functions. However, the roles of MAP kinases in neutrophils are not well understood yet. Protein phosphorylation analysis of cellular MAP kinases indicates that exposure of human neutrophils to chemotactic factor FMLP as well as granulocyte-macrophage CSF, PMA, or ionomycin rapidly induced the activation of p38 and p44/42 MAP kinases, but stimulation with inflammatory cytokine TNF-alpha triggered the activation of p38 MAP kinase only. To study the cellular functions of these MAP kinases, the inhibitor SB20358, which specifically inhibited enzymatic activity of cellular p38 MAP kinase, and the inhibitor PD98059, which specifically blocked the induced protein phosphorylation and activation of p44/42 MAP kinase in intact neutrophils, were utilized. Inhibition of the cellular p38 MAP kinase activation almost completely abolished the TNF-alpha-stimulated IL-8 production and superoxide generation of human neutrophils. In addition, the FMLP-induced neutrophil chemotaxis as well as superoxide generation were suppressed markedly by inhibiting the activation of cellular p38 MAP kinase, but not p44/42 MAP kinase. Moreover, RIA indicates that the activation of cellular p38 MAP kinase was required for the neutrophil IL-8 production stimulated by granulocyte-macrophage CSF or LPS as well as TNF-alpha, but not for that induced by PMA or ionomycin. These results demonstrate that the activation of cellular p38 MAP kinase is indispensable for the TNF-alpha- or FMLP-mediated cellular functions in human neutrophils, and suggest that p38 MAP kinase may play a different role in response to distinct stimulation.
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PMID:p38 mitogen-activated protein kinase activation is required for human neutrophil function triggered by TNF-alpha or FMLP stimulation. 946 62

Macrophage colony-stimulating factor (M-CSF) was found to be a glycoprotein with a molecular weight of 85 kDa which stimulated macrophage colony formation of mouse bone marrow cells in a semisolid agar culture system in 1978. M-CSF stimulates differentiation of progenitor cells to mature monocytes, and prolongs the survival of monocytes. It enhances expression of differentiation antigens and stimulates chemotactic, phagocytic and the killing activities of monocytes. Macrophage CSF also stimulates production of several cytokines such as granulocyte-macrophage CSF, granulocyte CSF and interleukin (IL)-6 by priming monocytes, and directly stimulates production and secretion of IL-8 and reactive nitrogen intermediates. In addition to the stimulation of hematopoiesis, M-CSF also stimulates differentiation and proliferation of osteoclast progenitor cells and cytotrophoblasts. Proteoglycan type M-CSF, which contains chondroitin sulfate chains, was found in 1992. In a large-scale double-blind controlled study on acute myeloid leukemia (AML), it has been shown that the administration of M-CSF to patients after consolidation chemotherapies shortens the periods of neutropenia and thrombopenia after chemotherapy and reduces the incidence and shortens the duration of febrile neutropenia, as well as shortening the period required to finish three courses of intensive consolidation therapy.
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PMID:Biological activities and clinical application of M-CSF. 963 77

Mast cells are found frequently in close proximity to blood vessels, and endothelial cells are likely to be exposed to high concentrations of their granule mediators. We have investigated the proinflammatory actions of the major mast cell product tryptase on HUVEC. Addition of purified tryptase was found to stimulate thymidine incorporation, but induced little alteration in cell numbers, suggesting it is not a growth factor for HUVEC. Expression of ICAM-1, VCAM-1, and E-selectin was not altered following incubation with tryptase, but the potent granulocyte chemoattractant IL-8 was released in a dose-dependent fashion in response to physiologically relevant concentrations, with maximal levels in supernatants after 24 h. The actions of tryptase on HUVEC were inhibited by heat inactivation of the enzyme, or by preincubating with the protease inhibitors leupeptin or benzamidine, suggesting a requirement for an intact catalytic site. Reverse-transcription PCR analysis indicated up-regulation of mRNA for IL-8 as well as for IL-1 beta in response to tryptase or TNF-alpha. However, tryptase was a more selective stimulus than TNF-alpha and did not induce increased expression of mRNA for granulocyte-macrophage CSF or stimulate the release of this cytokine. Leukocyte accumulation in response to tryptase may be mediated in part through the selective secretion of IL-8 from endothelial cells.
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PMID:The role of mast cell tryptase in regulating endothelial cell proliferation, cytokine release, and adhesion molecule expression: tryptase induces expression of mRNA for IL-1 beta and IL-8 and stimulates the selective release of IL-8 from human umbilical vein endothelial cells. 971 64

Endogenous proteolytic enzymes have been shown to be potential sources of airway inflammation inducing proinflammatory cytokine release from respiratory epithelial cells; however, whether any of the exogenous proteases from important allergen sources such as the house dust mite present in our environment behave in a similar fashion is unclear. To this end, we have investigated whether the mite cysteine and serine proteolytic allergens, Der p 1 and Der p 9, respectively, induced cytokine production from primary human bronchial epithelial cells and from the epithelial cell line BEAS-2B. Cells were exposed to mite proteases, and cells or supernatants were assayed for cytokine release, cytokine mRNA expression, and modulation of intracellular calcium ion concentration. Both proteases induced concentration- and time-dependent increases in the release of granulocyte-macrophage (GM)-CSF, IL-6, and IL-8 as well as an increase in the expression of IL-6 mRNA. Cytokine release and mRNA expression were first observed at 8 h and 2 h after protease exposure, respectively. The minimum concentration of each protease that was required to stimulate GM-CSF, IL-6, and IL-8 release was approximately 10 ng/ml. Cytokine release was initiated by 1 to 2 h of protease exposure, although maximum concentrations were detected only after a 24-h incubation. IL-6, but not IL-8 and GM-CSF, was shown to be degraded by both proteases at concentrations of > 2 microg/ml. The proteases also stimulated changes in the intracellular calcium ion concentration. All mite protease-induced phenomena were inhibited using appropriate protease inhibitors. These results suggest that the proteolytic activity of an allergen may stimulate the release of proinflammatory cytokines from human bronchial epithelium.
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PMID:Dust mite proteolytic allergens induce cytokine release from cultured airway epithelium. 975 88

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