Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both keratin synthesis and the formation of the horny layer are "classical" functions of human epidermal keratinocytes. In recent year a couple of interesting immunological functions of keratinocytes have been discovered. In the present review phagocytosis, production and secretion of cytokines (IL-1, IL-3, IL-6, IL-8, CSF, ECDF, IFN) and their ligands as well as the expression of selected cell surface receptors (HLA-DR, ICAM-1, Fc-gamma receptor) ligands are described.
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PMID:[The keratinocyte--a biologically active cell]. 169 21

In this in vitro study, the influence of serum-concentration, heat inactivation of the serum and the origin of the serum on the responsiveness of cultured human umbilical vein endothelial cells (HUVEC) to immunological challenges was investigated. Addition of human serum during stimulation with 1 microgram/ml bacterial lipopolysaccharide (LPS) increased endothelial cell ELAM-1 expression and interleukin (IL)-6 release five to ten-fold. Full endothelial cell responsiveness to LPS required 10 to 50% human serum and was largely abrogated after heating the serum for 30 minutes at 56 degrees C. Addition of newborn or fetal bovine serum instead of human serum, induced even higher IL-6 release and ELAM-1 expression in response to LPS, whilst heat-inactivation of these serum-batches only moderately decreased endothelial cell responses. Endothelial cell IL-6 release and ELAM-1 expression after stimulation with IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) were less influenced by heat inactivation of the serum and by omission of serum, whilst responses to PMA remained completely unaffected by such modifications in assay media. Finally, we demonstrated that endothelial cell IL-8 release also and ICAM-1 expression in response to LPS and cytokines were increased by addition of human serum, indicating that the use of serum-free assay media, or the use of media enriched with heat-inactivated (HI) human serum interferes with physiological endothelial cell responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:LPS and cytokine-induced endothelial cell IL-6 release and ELAM-1 expression; involvement of serum. 172 50

Interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) both induce polymorphonuclear leucocyte (PMNL) infiltration into tissues and they have a synergistic action in this respect. We and others have observed that IL-1 alpha and TNF-alpha induce 51Cr-labelled PMNL migration across monolayers of umbilical vein endothelium via an endothelial cell-dependent mechanism. Here we investigated the interaction of PMNL with fibroblasts, since PMNL probably encounter such cells in many tissues once they traverse the vascular wall. TNF-alpha, but not IL-1 alpha, was found to activate fibroblast monolayers, grown on polycarbonate filters, to stimulate PMNL transfibroblast migration. This was a time- and fibroblast-dependent process which required fibroblast protein synthesis, as indicated by inhibition with cycloheximide. The effect of TNF-alpha was not related to fibroblast chemotactic factor production (primarily IL-8), or to ICAM-1 up-regulation, since IL-1 was as active as TNF-alpha in this respect, without activating fibroblasts to support PMNL transfibroblast migration. Antiserum to IL-8, present during the assay, did not inhibit PMNL migration across the monolayers. The PMNL migration was highly dependent on the function of both CD11a (LFA-1) and CD11b (MAC-1) PMNL adhesion molecules, since monoclonal antibodies to either inhibited migration by about 80%. The results suggest a distinct activation by TNF-alpha of fibroblasts to facilitate PMNL migration through fibroblast barriers. These findings may in part account for the synergistic action of IL-1 and TNF-alpha in inducing extravascular accumulation of PMNL during inflammation.
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PMID:Tumour necrosis factor-alpha but not interleukin-1 induces polymorphonuclear leucocyte migration through fibroblast layers by a fibroblast-dependent mechanism. 193 64

Cytokines and cell adhesion receptors play a pivotal role in the recruitment of cells from the peripheral blood into inflamed tissue. Allergic rhinitis has previously been described as an inflammatory reaction characterised by the migration of granulocytes into the nasal mucosa. Using this model, we investigated the release of proinflammatory cytokines (interleukin IL-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha TNF-alpha) and the expression of cell adhesion molecules (ELAM-1, ICAM-1 and LFA-1) in two studies involving biopsies as well as lavage and brush techniques. IL-1 beta and TNF-alpha can be found rapidly after allergen exposure and seem to initiate the cellular infiltration. The release of the chemokine IL-8 correlates with the continuously increasing number of granulocytes on the mucosal surface. Allergic rhinitis subjects showed significantly increased secretion levels of the proinflammatory cytokines IL-1 beta and IL-6 and of the chemokine IL-8. These findings correspond to a higher expression of the adhesion receptors ELAM-1, ICAM-1 and LFA-1 in allergic mucosa. We conclude that proinflammatory cytokines regulate the cell infiltration by the induction of adhesion receptor expression.
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PMID:[The role of pro-inflammatory cytokines in recruiting inflammatory cells in the nose]. 751 83

Endothelial cells, as they normally exist in the vasculature as quiescent cells, perform several functions. In an inflammatory response, endothelial cells are activated to up-regulate a number of genes, including E-selectin (ELAM-1), VCAM-1, ICAM-1, interleukin (IL)-1, IL-8 and plasminogen activator inhibitor-1 (PAI-1). Very little is known about factors that regulate the activation process. We describe here that a heat-stable protein, normally present in the alpha-globulin fraction of serum, inhibits induced expression of E-selectin, ICAM-1, and VCAM-1 in vitro and also impedes the accumulation of mRNA for these molecules. Inhibition of E-selectin, the only gene tested in this respect, is at the level of transcription. At the same time, the alpha-globulins do not, under the same conditions, repress mRNA accumulation for IL-1, IL-8, or PAI-1. The effect of the inhibitor does not relate to constraints on function of nuclear-factor kappa B, the induced activity of which is not interfered with at the early time points at which the suppression of these three genes is seen.
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PMID:Selective inhibition of E-selectin, ICAM-1, and VCAM in endothelial cells. 752 66

We investigated the effect of interleukin-1 (IL-1) activation of human umbilical vein endothelium (HUVE) on human monocyte transendothelial migration induced by chemotactic factors. Monocyte migration across unactivated endothelium in response to macrophage inflammatory protein-1 alpha (MIP-1 alpha), RANTES, platelet-activating factor (PAF), or monocyte chemoattractant protein-1 (MCP-1) was completely inhibited (90%) by monoclonal antibodies (mAbs; 60.3) to CD18 of the CD11/CD18 complex on the monocyte and partially inhibited (by 75%) in response to C5a. When the HUVE was stimulated with IL-1 alpha (5 h, 0.1 ng/ml), monocyte migration in response to C5a, MIP-1 alpha, RANTES, or PAF was no longer inhibited by mAb to CD18. However, migration was blocked by the combination of mAb to the alpha 4-integrin (CD49d) chain of very late antigen-4 (CD49d/CD29) with the mAb to CD18. In contrast to the above stimuli, activation of the HUVE with IL-1 alpha inhibited the transendothelial migration of monocytes in response to MCP-1. mAbs to the adhesion molecules up-regulated on HUVE by IL-1, i.e., E-selectin (CD62E), intercellular adhesion molecule-1 (CD54) or vascular cell adhesion molecule-1 (CD106), did not reverse the inhibitory effect. Transendothelial migration in response to MCP-1 but not to C5a was inhibited by the treatment of monocytes with culture supernatant from IL-1 alpha-stimulated (but not from unstimulated) HUVE. Such supernatant contained chemotactic activity for monocytes, and a mAb to MCP-1 blocked the migration inhibitory effect of IL-1 activation of the HUVE monolayer, as well as the chemotactic activity in the supernatant from IL-1-stimulated HUVE. The inhibitory effect on migration of IL-1-stimulated HUVE was specific for monocytes because polymorphonuclear leukocyte transendothelial migration in response to IL-8 (a related chemokine) was not inhibited by IL-1 activation of HUVE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IL-1 activation of endothelium supports VLA-4 (CD49d/CD29)-mediated monocyte transendothelial migration to C5a, MIP-1 alpha, RANTES, and PAF but inhibits migration to MCP-1: a regulatory role for endothelium-derived MCP-1. 754 7

Treatment of human endothelial cells with cytokines such as interleukin-1, tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma induces the expression of specific leukocyte adhesion molecules on the endothelial cell surface. Interfering with either leukocyte adhesion or adhesion protein upregulation is an important therapeutic target as evidenced by the potent anti-inflammatory actions of neutralizing antibodies to these ligands in various animal models and in patients. In the present study we report that cotreatment of human endothelial cells with certain hydroxyflavones and flavanols blocks cytokine-induced ICAM-1, VCAM-1, and E-selectin expression on human endothelial cells. One of the most potent flavones, apigenin, exhibited a dose- and time-dependent, reversible effect on adhesion protein expression as well as inhibiting adhesion protein upregulation at the transcriptional level. Apigenin also inhibited IL-1 alpha-induced prostaglandin synthesis and TNF-alpha-induced IL-6 and IL-8 production, suggesting that the hydroxyflavones may act as general inhibitors of cytokine-induced gene expression. Although apigenin did not inhibit TNF-alpha-induced nuclear translocation of NF-kappa B(p50(NFKB1)/p65(RelA)) we found this flavonoid did inhibit TNF-alpha induced beta-galactosidase activity in SW480 cells stably transfected with a beta-galactosidase reporter construct driven by four NF-kappa B elements, suggesting an action on NF-kappa B transcriptional activation. Adhesion of leukocytes to cytokine-treated endothelial cells was blocked in endothelial cells cotreated with apigenin. Finally, apigenin demonstrated potent anti-inflammatory activity in carrageenan induced rat paw edema and delayed type hypersensitivity in the mouse. We conclude that flavonoids offer important therapeutic potential for the treatment of a variety of inflammatory diseases involving an increase in leukocyte adhesion and trafficking.
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PMID:Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression. 763 22

Endothelial cell activation is achieved by the rapid, protein synthesis-independent induction of a characteristic set of genes. Because of the abundance of binding sites for the transcription factor NF-kappa B in the regulatory region of the aforementioned genes, we hypothesized that this factor might play a key role. Reactive oxygen intermediates act as second messengers in the activation of NF-kappa B. We have used the antioxidant pyrrolidine dithiocarbamate to analyze the effect of NF-kappa B inhibition on TNF alpha-induced EC activation in vitro. We show that pyrrolidine dithiocarbamate strongly reduces the TNF alpha-mediated induction of E-selectin, VCAM-1, ICAM-1, PAI-1, tissue factor, IL-8 and I kappa B-alpha. We present evidence identifying NF-kappa B as a central of EC activation. Therefore, this factor may represent a prime target for therapeutic intervention in pathologic conditions associated with EC activation such as allo- and xenograft rejection, atherosclerosis, ischemic reperfusion injury and vasculitis.
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PMID:Inhibition of NF-kappa B by pyrrolidine dithiocarbamate blocks endothelial cell activation. 754 93

Leukocyte recruitment is a key step in the inflammatory reaction. Several changes in the cell morphology take place during lymphocyte activation and migration: spheric-shaped resting T cells become polarized during activation, developing a well defined cytoplasmic projection designated as cellular uropod. We found that the chemotactic and proinflammatory chemokines RANTES, MCP-1, and, to a lower extent, MIP-1 alpha, MIP-1 beta, and IL-8, were able to induce uropod formation and ICAM-3 redistribution in T lymphoblasts adhered to ICAM-1 or VCAM-1. A similar chemokine-mediated effect was observed during T cells binding to the fibronectin fragments of 38- and 80-kD, that contain the binding sites for the integrins VLA-4 and VLA-5, respectively. The uropod structure concentrated the ICAM-3 adhesion molecule (a ligand for LFA-1), and emerged to the outer milieu from the area of contact between lymphocyte and protein ligands. In addition, we found that other adhesion molecules such as ICAM-1, CD43, and CD44, also redistributed to the lymphocyte uropod upon RANTES stimulation, whereas a wide number of other cell surface receptors did not redistribute. Chemokines displayed a selective effect among different T cell subsets; MIP-1 beta had more potent action on CD8+ T cells and tumor infiltrating lymphocytes (TIL), whereas RANTES and MIP-1 alpha targeted selectively CD4+ T cells. We have also examined the involvement of cAMP signaling pathway in uropod formation. Interestingly, several cAMP agonists were able to induce uropod formation and ICAM-3 redistribution, whereas H-89, a specific inhibitor of the cAMP-dependent protein kinase, abrogated the chemokine-mediated uropod formation, thus pointing out a role for cAMP-dependent signaling in the development of this cytoplasmic projection. Since the lymphocyte uropod induced by chemokines was completely abrogated by Bordetella pertussis toxin, the formation of this membrane projection appears to be dependent on G proteins signaling pathways. In addition, the involvement of myosin-based cytoskeleton in uropod formation and ICAM-3 redistribution in response to chemokines was suggested by the prevention of this phenomenon with the myosin-disrupting agent butanedione monoxime. Interestingly, this agent also inhibited the ICAM-3-mediated cell aggregation, but not the cell adhesion to substrata. Altogether, these results demonstrate that uropod formation and adhesion receptor redistribution is a novel function mediated by chemokines; this phenomenon may represent a mechanism that significantly contributes to the recruitment of circulating leukocytes to inflammatory foci.
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PMID:Chemokines regulate cellular polarization and adhesion receptor redistribution during lymphocyte interaction with endothelium and extracellular matrix. Involvement of cAMP signaling pathway. 759 74

The majority of T cells at the site of an inflammatory lesion do not appear to be Ag-specific, but they still contribute to the inflammatory response. Herein, we report that sCD23 activates monocytes to participate in the stimulation of resting T cells in the absence of TCR engagement. First, sCD23 selectively triggers monokine release by purified monocytes in the absence of costimulus. It induces TNF-alpha, IL-1 beta, IL-8, granulocyte-macrophage-CSF, and prostaglandin E2 but no IL-10, IL-12, TGF-beta, or leukotriene B4. The sCD23-induced TNF-alpha production is significantly inhibited by IL-4 and IL-10 but not by TGF-beta. Also, monocytes activated by sCD23 express decreased levels of HLA-DR and increased levels of CD14, CD54, CD40, and B7 Ag. Next, we show that, in the presence of monocytes, sCD23 is a potent costimulator of IL-2 or IL-12-induced IFN-gamma production by resting T cells in the absence of exogenous Ag and that this effect is partially reduced by anti-TNF-alpha mAb. B cells cannot substitute for monocytes, and CD4+ and CD8+ T cells are equal responders. The data further indicate that monocyte-T cell contact, more particularly CD40-CD40L interactions, is required for IFN-gamma production in response to IL-2 plus sCD23, and the response to IL-12 plus sCD23 is CD40- and B7-independent but is still partially contact-dependent. It is proposed that sCD23, when produced locally at a site of immune response, may trigger an inflammatory process via monokine release and may further amplify it via the stimulation of bystander non-Ag-specific T cells.
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PMID:Soluble CD23 directly activates monocytes to contribute to the antigen-independent stimulation of resting T cells. 759 90


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