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)

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

Effective hematopoiesis is usually induced by interactions between hematopoietic progenitor cells (HPC) and stromal cells. In cord blood (CB), umbilical vein endothelial cells (HUVEC) can support HPC as a stromal microenvironment. EC activated mainly by IL-1 and TNFalpha produce a variety of cytokines and growth factors such as IL-1, IL-4, IL-6, GM-CSF and G-CSF. Since HPC express c-kit on their surface, the SCF produced by HUVEC plays an important role in the hematopoiesis of CB. We examined the expression of cytokines and growth factors on HUVEC by PCR. Resting HUVEC expressed high level of SCF, and low levels of IL-6, IL-7, and IL-8. Thus, a variety of cytokines and growth factors are produced by EC, and this cytokine network is thought to play an important role in regulating hematopoiesis. Activated EC can also express various adhesion molecules including E-selectin, VCAM-1 and ICAM-1, and facilitate the adhesion of hematopoietic cells to the endothelium. Furthermore, the interaction of CB cells with HUVEC has recently been shown in vitro. We previously showed that the culture media of HUVEC induced high numbers of colony formation. Suitable cytokine productions are thus provided to HPC by the interaction of HUVEC and cord MNC. On the basis of these findings, several mechanisms to support hematopoiesis in CB can be considered. Specific growth factors produced by EC bind to HPC to induce proliferation. While cell-cell interactions involve adhesion of HPC to HUVEC via adhesion molecules, and the adhesion of HPC to EC will facilitate interaction with cytokines and growth factors. Thus HPC in CB proliferate and are maintained by growth factors, and adhesion molecules produced by HUVEC, and HPC themselves.
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PMID:Role of umbilical vein endothelial cells in hematopoiesis. 972 Jul 15

In keeping with the multistep model of leukocyte-endothelial cell interaction, stimulation of endothelium by cytokines or endotoxin (LPS) in vitro leads to selectin/integrin-mediated neutrophil adhesion, followed by neutrophil endothelial transmigration. The i.p. injection of LPS in vivo induces a systemic inflammatory reaction in a mouse model with generalized activation of both endothelial cells (up-regulation of adhesion molecules ICAM-1, VCAM-1, E-selectin) and neutrophils (up-regulation of Mac-1). However, no intravascular endothelial adhesion or tissue emigration of neutrophils can be observed. Even more importantly, the in vivo emigration of polymorphonuclear cells at sites of a local inflammatory reaction (IL-8, TNF, LPS) is totally inhibited when the mice are pretreated systemically with LPS, although the neutrophils respond fully to a rechallenge with LPS ex vivo, and endothelial adhesion molecules are further up-regulated locally. The systemic application of TNF also caused a total inhibition of neutrophil emigration. However, while anti-TNF mAb abrogated the inhibitory activity induced by TNF, they had no effect on systemic LPS. The systemic application of IL-8 did not inhibit neutrophil emigration, nor did the pretreatment of mice with anti-IL-8 mAb before the systemic application of LPS abrogate the inhibitory activity induced by LPS. Therefore, the putative inhibitor of neutrophil emigration, which may be of great physiologic importance, as it prevents in vivo the generalized emigration of activated neutrophils, most likely is not IL-8.
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PMID:Inhibition of leukocyte emigration induced during the systemic inflammatory reaction in vivo is not due to IL-8. 975 86

Proinflammatory effects induced by the serine protease factor Xa were investigated in HUVEC. Exposure of cells to factor Xa (5-80 nM) concentration dependently stimulated the production of IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) and the expression of E-selectin, ICAM-1, and VCAM-1, which was accompanied by polymorphonuclear leukocyte adhesion. The effects of factor Xa were blocked by antithrombin III, but not by the thrombin-specific inhibitor hirudin, suggesting that factor Xa elicits these responses directly and not via thrombin. IL-1alpha and TNF-alpha were not implicated, since neither the IL-1 receptor antagonist nor a TNF-neutralizing Ab could suppress the factor Xa responses. Active site-inhibited factor Xa and factor Xa depleted from gamma-carboxyglutamic acid residues were completely inactive. The effector cell protease receptor-1 (EPR-1) seems not to be involved since anti-EPR-1 Abs failed to inhibit cytokine production. Moreover, neither the factor X peptide Leu83-Leu88, representing the inter-epidermal growth factor sequence in factor Xa that mediates ligand binding to EPR-1, nor the peptide AG1, corresponding to the EPR-1 sequence Ser123-Pro137 implicated in factor Xa binding, inhibited the factor Xa-induced cytokine production. In conclusion, these findings indicate that factor Xa evokes a proinflammatory response in endothelial cells, which requires both its catalytic and gamma-carboxyglutamic acid-containing domain. The receptor system involved in these responses induced by factor Xa remains to be established.
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PMID:Factor Xa induces cytokine production and expression of adhesion molecules by human umbilical vein endothelial cells. 978 Feb 8

We hypothesized that blocking the induction of proinflammatory genes associated with endothelial cell (EC) activation, by inhibiting the transcription factor nuclear factor kappaB (NF-kappaB), would prolong survival of vascularized xenografts. Our previous studies have shown that inhibition of NF-kappaB by adenovirus-mediated overexpression of I kappaB alpha suppresses the induction of proinflammatory genes in EC. However, I kappaB alpha sensitizes EC to TNF-alpha-mediated apoptosis, presumably by suppressing the induction of the NF-kappaB-dependent anti-apoptotic genes A20, A1, manganese superoxide dismutase (MnSOD), and cellular inhibitor of apoptosis 2. We report here that adenovirus mediated expression of a dominant negative C-terminal truncation mutant of p65/RelA (p65RHD) inhibits the induction of proinflammatory genes, such as E-selectin, ICAM-1, VCAM-1, IL-8, and inducible nitric oxide synthase, in EC as efficiently as does I kappaB alpha. However, contrary to I kappaB alpha, p65RHD does not sensitize EC to TNF-alpha-mediated apoptosis although both inhibitors suppressed the induction of the anti-apoptotic genes A20, A1, and MnSOD equally well. We present evidence that this difference in sensitization of EC to apoptosis is due to the ability of p65RHD, but not I kappaB alpha, to inhibit the constitutive expression of c-myc, a gene involved in the regulation of TNF-alpha-mediated apoptosis. These data demonstrate that it is possible to block the expression of proinflammatory genes during EC activation by targeting NF-kappaB, without sensitizing EC to apoptosis and establishes the role of c-myc in controlling induction of apoptosis during EC activation. Finally, these data provide the basis for a potential approach to suppress EC activation in vivo in transgenic pigs to be used as donors for xenotransplantation.
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PMID:Adenovirus-mediated expression of a dominant negative mutant of p65/RelA inhibits proinflammatory gene expression in endothelial cells without sensitizing to apoptosis. 979 84

Although they are considered as destructive agents, free radicals can sometimes become useful. Their presence is intimately coupled with the activity of certain hemal oxydases which insert an atom of oxygen into their substrate by a stereospecific radical mecanism. The cytochromes P450 and the enzymes of the eicosanoide metabolism are some examples. The free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract or to infer a myorelaxation. They can even play the role of neurotransmitters such as azote monoxyde. The activation of phagocytes, which is an essential event in the inflammatory reaction, integrates these notions at several levels: in the mechanisms of bacterial death, in the spread of the inflammatory reaction and in the alteration of the extra-cellular matrix. The inflammatory reaction is initiated by interactions between vascular endothelium, platelets and leukocytes including signal exchanges, adhesion molecule expression and secretion of chimiotactic mediators. Activation of vascular endothelium is a key event in the initiation of the phenomenon. The cells intervening in the precocious inflammatory phase were tissular mastocytes and platelet-liberating mediators (histamine) and neutrophile cells responsible for vascular injuries induced by oxygen free radicals and nitric oxide. Reactive oxygen intermediates play a critical role, primarily to limit tissue damage and prevent or inhibit infection, secondary to enhancing and prolonging reaction. The monocytes and platelets liberate cytokines early, which appears to be important in activation and production of an inflammatory response. In fact, cytokines, especially TNF alpha and IL-1, induce synthesis and secretion endothelial adhesion molecules such as ICAM-1, VCAM-1 and E-selectin, which have been demonstrated to mediate leukocyte recruitment to sites of inflammation. The cytokines also activate the fibroblasts and endothelial cells that produce, among others, free radicals and other chimiotactic cytokines of which some (IL-8 and related) can induce neutrophil degranulation and stimulate oxidative stress and formation of free radicals. Furthermore, endothelial cells have been shown to make use of a broad repertoire of cytokines including IL-1, IL-6, IL-8, MCP-1 and gro/MGSA, which may be secreted during an inflammatory response and exercise pro-inflammatory functions. Under the influence of the inflammatory mediators, other enzymes are also activated. The inducible isoforms of cyclo-oxygenase (COX-2) and nitric oxide synthase (iNOS) play an important role in inflammatory reactions via the production respectively of prostaglandins and nitric oxide. The induction of cell adhesion molecules (ICAM-1, VCAM-1 and E-selectin), cytokines, acute phase proteins, growth factors, COX-2 and iNOS expression is mediated by the activation of transcriptional factors, especially the nuclear factor kappa B (NF-kappa B). The NF-kappa B system is essentially involved in immediate early expression of various immunoregulatory genes and has been demonstrated to represent an important regulatory system of endothelial activation. The target genes for NF-kappa B comprise a growing list of genes intrinsically linked to a coordinated inflammatory response. The NF-kappa B is a heterodimer composed of two subunits (p65 and p50). In non-stimulated cells, NF-kappa B resides in the cytoplasm as an inactive complex bound to its inhibitor, I kappa B. Upon stimulation with various agents including cytokines, mitogenes, viruses and reactive oxygen intermediates, I kappa B dissociates from the NF-kappa B-I kappa B complex and translocates to the nucleus, binding with high affinity to specific sites in the promoter regions of target genes and stimulating their transcription. In the case of any weakness of this anti-oxidizing defence or any over-production of radical species, a state of oxidative stress occurs. (ABSTRACT TRUNC
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PMID:[Free radicals and antioxidants: physiology, human pathology and therapeutic aspects (part II)]. 980 2

Perivascular infiltrates of inflammatory cells are a hallmark of lesional skin in scleroderma. We have explored the potential for scleroderma fibroblasts to modulate mononuclear leucocyte migration across endothelial cell monolayers in tissue culture, and to regulate expression of endothelial cell adhesion molecules. Fibroblasts were grown from skin biopsies of eight patients with active diffuse cutaneous scleroderma and from four healthy controls. Co-culture and conditioned medium transfer experiments examined the effect of soluble fibroblast products on mononuclear leucocyte (U937) cell migration across endothelial cell (1E-7) monolayers grown on tissue culture inserts. Co-culture of scleroderma, but not control fibroblasts, promoted transendothelial migration of U937 cells. Scleroderma fibroblast-conditioned medium had qualitatively similar effects and equivalent results were obtained using Jurkat-6 (T lymphocyte) cells, and with peripheral blood mononuclear cells from a patient with diffuse cutaneous scleroderma. Promotion of leucocyte migration does not appear to result from increased endothelial adhesion molecule expression, since fibroblast-conditioned medium did not up-regulate endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) or E-selectin. Moreover, leucocyte migration across cytokine-activated endothelial cell layers in co-culture with fibroblasts was less than across resting cells, although the selective effect of scleroderma fibroblast co-culture persisted. Recombinant monocyte chemoattractant protein-1 (MCP-1) or IL-8 increased passage of mononuclear leucocytes across endothelial cell monolayers, whilst anti-MCP-1, but not anti-IL-8 antibodies, significantly reduced the effect of fibroblast conditioned medium. These data suggest that systemic sclerosis (SSc) fibroblasts promote leucocyte migration across endothelial cell monolayers in tissue culture via an MCP-1-dependent mechanism. These findings may be relevant to the perivascular mononuclear leucocyte infiltrates characteristic of early SSc lesions.
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PMID:Scleroderma fibroblasts promote migration of mononuclear leucocytes across endothelial cell monolayers. 982 90

We investigated the effect of TNF alpha, IL-1alpha and IFN gamma on two neuroblastoma (NB) cell lines (SK-N-SH and SK-N-MC). These lines responded differentially to IL-1alpha, TNF alpha and IFN gamma for MCP-1 and IL-8 production and expression of the ICAM-1 and VCAM-1 adhesion molecules. None of the cytokines induced MCP-1 or IL-8 on SK-N-MC cells. Both chemokines were produced in response to IL-1alpha by SK-N-SH cells, while TNF alpha induced mainly MCP-1 production. Addition of IFN gamma decreased IL-8, but not MCP-1 production. These responses correlated with monocyte and neutrophil chemotactic activity in NB culture supernatants. This activity was neutralized by antibodies to IL-8 and MCP-1. The expression of ICAM-1 on SK-N-MC was up-regulated by TNF alpha or IFN gamma, while IL-1alpha also upregulated ICAM-1 on SK-N-SH cells. VCAM-1 expression on SK-N-SH was induced by IL-1alpha and TNF alpha and IFN gamma synergized with TNF alpha in this respect on both NB cell lines. These results suggest that mechanisms for chemokine production and VCAM-1 and ICAM-1 upregulation by inflammatory cytokines differ and IFN gamma, in conjunction with TNF alpha, stimulate neural cell responses (high MCP-1 and VCAM-1 and decreased IL-8) favouring mononuclear cell recruitment.
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PMID:Chemokine production and adhesion molecule expression by neural cells exposed to IL-1, TNF alpha and interferon gamma. 982 72

Endothelial cell dysfunction is a classic consequence of radiation damage. Bone marrow endothelial cells (BMEC) are a critical component of the stroma in the regulation of haemopoiesis. In animal models, radiation-induced injury of BMEC has been described and a role for BMEC in haemopoietic regeneration after irradiation has been suggested. However, functions of BMEC involved in the haemopoietic regeneration have not been assessed. Therefore we studied the functional response of human BMEC to irradiation using the transformed human BMEC line (TrHBMEC) irradiated with 2. 5 or 10Gy. Our results showed a time- and a dose-dependent increase in damage to irradiated TrHBMEC measured by a decreased number of adherent cells which correlated with increased apoptosis and augmented release of soluble ICAM-1 and von Willebrand factor. 2 Gy irradiated TrHBMEC expressed more ICAM-1 on their surface than non-irradiated cells, whereas no change in VCAM-1, E-selectin and PECAM-1 expression was observed. An increased production of G-CSF, GM-CSF, IL-8, IL-6, IL-1alpha, IL-11, MIP-1alpha and SCF and no production of LIF, TNF-alpha, TPO and IL-3 by 2 Gy irradiated TrHBMEC was observed. The haemopoietic supportive function of TrHBMEC was not altered after a 2 Gy exposure. These results suggest that although radiation induces endothelial cell damage, irradiated cells still support the proliferation and the differentiation of CD34+ haemopoietic cells.
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PMID:Characterization of the response of human bone marrow endothelial cells to in vitro irradiation. 988 9

Endothelial activation is a central feature of preservation-induced allograft injury. The present study aims at a quantitative assessment of stress proteins, adhesion molecules, and interleukin-8 in a cell culture-based model of organ preservation. Human umbilical vein endothelial cells were exposed to cold, hypoxic storage in University of Wisconsin (UW), histidine-tryptophane-ketoglutarate (HTK), and EuroCollins solutions for 8 h with subsequent rewarming/reoxygenation (rew/reox) for 1 and 4 h. A cell-based ELISA was designed for detection of heat shock proteins (HSP) 60 and 70, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). Immunohistochemical staining was performed for comparison. Interleukin-8 was quantified by ELISA. HSP 70 was expressed after cold storage in HTK and EuroCollins solution and after rew/reox in all groups. A constitutive expression of HSP 60 was observed with further upregulation after rew/reox following cold storage in all experimental groups. ICAM-1 was clearly upregulated, but VCAM-1 showed only weak expression after cold storage and rew/reox. ELAM-1 was detectable in minimal amounts after cold storage but was considerably upregulated after 4 h of rew/reox. A significant increase of interleukin-8 release could be found after 4 h of rew/reox following storage in EuroCollins solution. Expression of stress proteins can be considered as a new parameter of preservation-associated endothelial activation. Apart from possible protective effects, allograft vasculopathy could be in part a consequence of the antigeneic potential of heat shock proteins connected with effects caused by adhesion molecules and inflammatory cytokines.
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PMID:Expression of stress proteins, adhesion molecules, and interleukin-8 in endothelial cells after preservation and reoxygenation. 1019 Oct 34

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