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

Numerous studies indicate that enteroviruses, such as the Coxsackievirus (CV) group, are linked to autoimmune diseases. Virus tropism and tissue access are modulated by vascular endothelial cells (ECs), mainly at the level of the microvasculature. Data on the permissiveness of ECs to CV are, however, scanty and derived from studies on large vessel ECs. To examine the susceptibility of microvascular ECs to infection of group B CV (CVB), human dermal microvascular ECs (HMEC-1) were infected with three CVB strains, and the immunological phenotype of the infected cells was analyzed. All CVB persistently infected the EC cultures without producing overt cytopathic effects. Infected ECs retained endothelial characteristics. Release of infectious particles in cell supernatants persisted for up to 3 mo of culture. Infection up-regulated expression of the adhesion molecules ICAM-1 and VCAM-1, with the highest values detected during the first 30 days of infection (p < 0.05 vs uninfected HMEC-1). CVB infection increased production of the proinflammatory cytokines, IL-6, IL-8, and TNF-alpha, which may account for the enhanced expression of adhesion molecules. Parallel infection of macrovascular HUVEC had less evident effects on induction of ICAM-1 and did not significantly increase expression of VCAM-1. Moreover, mononuclear cell adhesion to CVB-infected HMEC-1 monolayers was increased, compared with uninfected monolayers. These results provide evidence that small vessel ECs can harbor a persistent viral infection, resulting in quantitative modification of adhesion molecule expression, which may contribute to the selective recruitment of subsets of leukocytes during inflammatory immune responses. Furthermore, our data confirm that the behavior against a viral challenge of ECs in large vessels and microvessels may differ.
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PMID:Persistent infection of human microvascular endothelial cells by coxsackie B viruses induces increased expression of adhesion molecules. 1281 28

An understanding of the endothelial cell/blood/biomaterial interactions is central to advancing the success of cardiovascular devices that continue to fail because of the lack of nonthrombogenic biomaterials. A simplified endothelial cell/blood cell/biomaterial static model was used to assess these interactions. Human whole blood or isolated blood cells (mononuclear cells, neutrophils, platelets) were pretreated with biomaterial beads with different surface chemistries: polystyrene (PS), PS beads grafted with 3-kDa polyethylene glycol (PEG) with either hydroxyl (PS-PEG-OH) or amine (PS-PEG-NH2) terminal groups at bead concentrations of 5.4 or 54 x 10(4) beads/mL. Leukocyte and platelet activation and microparticle formation was assessed using flow cytometry. Biomaterial-activated whole blood or isolated cells or mononuclear cell fractions were applied to human umbilical cord endothelial cells (HUVEC) for static coculture, and the resultant proinflammatory HUVEC phenotype was characterized. ICAM-1 and E-selectin expression on HUVEC was increased after 4-h static coculture with biomaterial-treated human whole blood or mononuclear cells but not neutrophils or platelets. VCAM-1 expression on HUVEC was similarly increased after 24-h static coculture but not after 4 h of coculture. Increased concentrations of cytokines, IL-6, IL-8, and MCP-1, were detected in the supernatant of cocultures of HUVEC with biomaterial-treated whole blood or mononuclear cells but not neutrophils or platelets, compared with the media control. After 24 h, cytokine release was significantly increased for both IL-8 and MCP-1 but not IL-6 above concentrations after 4 h of coculture. Neither the cell adhesion molecule (CAM) expression nor cytokine release induced by coculture with biomaterial-treated whole blood or isolated cells was dependent on either material surface chemistry or material surface area. The changes in HUVEC CAM expression and cytokine release induced by biomaterial-treated mononuclear cells can be attributed predominantly to adherent cells on beads and nonadherent bulk cells with moderate regulation by the soluble supernatant; however, mononuclear cell-derived microparticles induced no significant changes in CAM expression or cytokine release after static coculture with HUVEC.
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PMID:Proinflammatory phenotype of endothelial cells after coculture with biomaterial-treated blood cells. 1287 Apr 71

Gastroesophageal reflux disease is the most common malady of the esophagus, affecting 7% of the United States population. Histological assessment demonstrates classic inflammatory mechanisms including selective leukocyte recruitment and hemorrhage, suggesting a prominent role for the microvasculature. We isolated and characterized human esophageal microvascular endothelial cells (EC) (HEMEC), examined inflammatory activation in response to cytokines, LPS, and acidic pH exposure, and identified signaling pathways that underlie activation. HEMEC displayed characteristic morphological and phenotypic features including acetylated LDL uptake. TNF-alpha/LPS activation of HEMEC resulted in upregulation of the cell adhesion molecules (CAM) ICAM-1, VCAM-1, E-selectin, and mucosal addressin CAM-1 (MAdCAM-1), increased IL-8 production, and enhanced leukocyte binding. Both acid and TNF-alpha/LPS activation lead to activation of SAPK/JNK in HEMEC that was linked to VCAM-1 expression and U-937 leukocyte adhesion. Expression of constitutive inducible nitric oxide synthase in HEMEC was in marked contrast to intestinal microvascular endothelial cells. In this study, we demonstrate that HEMECs are phenotypically and functionally distinct from lower gut-derived endothelial cells and will facilitate understanding of inflammatory mechanisms in esophageal inflammation.
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PMID:Isolation and characterization of human esophageal microvascular endothelial cells: mechanisms of inflammatory activation. 1291 42

Naturally acquired infections with Francisella tularensis, the bacterial agent of tularemia, occur infrequently in humans. However, the high infectivity and lethality of the organism in humans raise concerns that it might be exploited as a weapon of bioterrorism. Despite this potential for illicit use, the pathogenesis of tularemia is not well understood. To examine how F. tularensis interacts with cells of its mammalian hosts, we tested the ability of a live vaccine strain (LVS) to induce proinflammatory changes in cultured HUVEC. Living F. tularensis LVS induced HUVEC to express the adhesion molecules VCAM-1 and ICAM-1, but not E-selectin, and to secrete the chemokine CXCL8, but not CCL2. Stimulation of HUVEC by the living bacteria was partially suppressed by polymyxin B, an inhibitor of LPS, but did not require serum, suggesting that F. tularensis LVS does not stimulate endothelium through the serum-dependent pathway that is typically used by LPS from enteric bacteria. In contrast to the living organisms, suspensions of killed F. tularensis LVS acquired the ability to increase endothelial expression of both E-selectin and CCL2. Up-regulation of E-selectin and CCL2 by the killed bacteria was not inhibited by polymyxin B. Exposure of HUVEC to either live or killed F. tularensis LVS for 24 h promoted the transendothelial migration of subsequently added neutrophils. These data indicate that multiple components of F. tularensis LVS induce proinflammatory changes in endothelial cells in an atypical manner that may contribute to the exceptional infectivity and virulence of this pathogen.
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PMID:Francisella tularensis selectively induces proinflammatory changes in endothelial cells. 1292 7

Summary beta2-adrenoreceptor agonists are able to modulate various aspects of airway cell functions involved in the inflammatory and repair processes characterizing a variety of respiratory disorders. Human bronchial epithelial cells (HBECs), which can act as immune effector cells and express beta2-adrenoreceptors, were used to test the effects of different concentrations (0.1-100.0 nM) of salmeterol (Salm) on adhesion molecule expression and chemokine/cytokine release. HBECs, freshly isolated from resected bronchi at the time of surgery in ex-smokers with lung cancer, constitutively expressed over 3 times more ICAM-1 than VCAM-1 (P<0.05) and secreted greater amounts of IL-8 than of GM-CSF or RANTES (P<0.001). Stimulation of HBECs with IL-4, TNF-alpha or IL-4 plus TNF-alpha-upregulated ICAM-1 expression (P<0.05) and increased GM-CSF and IL-8 secretion (P<0.05). Similarly, VCAM-1 expression was significantly increased by IL-4 plus TNF-alpha, while RANTES release was significantly enhanced by IL-4 or by IL-4 plus TNF-alpha (P<0.05), but not by TNF-alpha alone (P>0.05). Dose-response curves showed that Salm, at concentration >1.0 nM, was effective in inhibiting adhesion molecule expression and cytokine release by HBECs (P<0.05). At a Salm concentration of 10 nM the degree of inhibition observed was similar for ICAM-1 and VCAM-1 expression (37.2 +/- 9.3% and 32.9 +/- 9.6%, respectively; P>0.05), but higher for RANTES (88.4 +/- 4.4%), as compared to IL-8 (21.8 +/- 7.0%) or GM-CSF (30.1 +/- 6.6%; P<0.05, each comparison). Thus, adhesion molecules and cytokines may be expressed/released at very different levels by unstimulated or stimulated HBECs and those activities appear to be modulated by Salm.
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PMID:Cytokine release and adhesion molecule expression by stimulated human bronchial epithelial cells are downregulated by salmeterol. 1450 60

When exposed to proinflammatory mediators, human bronchial epithelial cells (HBECs) upregulate the 'constitutive' adhesion molecule expression and cytokine/chemokine release. We tested whether and to what extent the inhibitory effect of fluticasone propionate on HBECs could involve the 'constitutive' and 'cytokine-induced' proinflammatory functions. Stimulation of the HBECs with interleukin (IL)-4 plus tumour necrosis factor (TNF)-alpha was more effective in upregulating intercellular adhesion molecule (ICAM)-1 ( approximately 2.2-fold increase) than vascular adhesion molecule (VCAM)-1 ( approximately 1.6-fold increase) expression (P<0.05) and in increasing the release of 'regulated on activation normal T cell expressed' (RANTES, 5.7-fold increase) than of IL-8 (3.5-fold increase) and granulocyte macrophage-colony stimulating factor (GM-CSF, 2.8-fold increase), (P<0.01). Fluticasone propionate, at the two concentrations tested (10 and 100 nM), was more effective in inhibiting the 'IL-4 plus TNF-alpha-induced' ICAM-1 expression than VCAM-1 expression (P<0.05) and in downregulating RANTES than IL-8 or GM-CSF secretion (P<0.05). The degree of inhibition demonstrated by fluticasone propionate appeared to be related to the degree of cell activation. In addition, for both adhesion molecules, the effect of fluticasone propionate at both concentrations tested appeared to be related to a complete inhibition of 'IL-4 plus TNF-alpha-induced' expression with no involvement of the 'constitutive' expression. Slightly different results were observed for cytokine/chemokine release. Indeed, evaluating RANTES, a complete inhibition of the 'IL-4 plus TNF-alpha-induced' release with a partial inhibition also of the 'constitutive' release at both concentrations of the drug tested was found, whereas for GM-CSF and IL-8, only a partial inhibition of the 'IL-4 plus TNF-alpha-induced' release in the presence of fluticasone propionate 10 and 100 nM. Thus, HBECs can constitutively or upon activation express adhesion molecules and secrete proinflammatory proteins at various levels and the different ability of fluticasone propionate to modulate the HBEC functions appears to be mostly related to the different inhibition of the various 'IL-4 plus TNF-alpha-induced' responses.
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PMID:Modulation of the constitutive or cytokine-induced bronchial epithelial cell functions in vitro by fluticasone propionate. 1455 81

Large-scale trials established that statin administration in hypercholesterolaemic individuals and patients with coronary heart disease (CHD) significantly reduces the risk of vascular events and death. This benefit was primarily attributed to their actions on lipids. This review focuses on the benefits (clinical and experimental) of statins observed soon (approximately 12 weeks) after their administration. Statins rapidly increase nitric oxide production and improve endothelial function (e.g. increased flow-mediated dilatation). Similarly, antioxidant properties decrease the susceptibility of low density lipoprotein cholesterol to oxidation. Statins inhibit the migration of macrophages and smooth muscle cell proliferation leading to an antiproliferative effect and the stabilisation of atherosclerotic plaques. Anti-inflammatory effects include a reduction in serum C-reactive protein levels, inflammatory and proinflammatory cytokines (e.g. IL-6, IL-8), adhesion molecules (e.g. ICAM-1, VCAM-1) and other acute phase proteins. Statins influence the haemostatic system. They reduce tissue factor expression and platelet activity, whereas fibrinolysis can be enhanced. Statins improve microalbuminuria, renal function, hypertension and arterial wall stiffness. A significant reduction of the carotid intima media thickness (IMT) was also reported early after statin treatment. These early effects of statins probably contribute to the significant reduction in vascular events seen in some 'short-term' studies. There is a need to further elucidate the rapid and non-lipid lowering properties of statins.
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PMID:Early vascular benefits of statin therapy. 1459 27

The aim of this study was to determine whether Desulfovibrio desulfuricans-derived LPS stimulate the release of IL-6 and IL-8 from ECs and the expression of their adhesion molecules at the transcriptional level. Confluent monolayers of HUVEC were incubated in the absence or presence of 20 microg/ml and 60 microg/ml LPSs derived from the DdT and DdA bacterial strains. Also, the simultaneous stimulation of cells with LPSs and IL-1beta was evaluated. The levels of cytokines released were measured using ELISA. LPS-activated HUVEC increased the secretion of both IL-6 and IL-8, which was not LPS dose dependent. The expression of E-selectin and VCAM-1 was assessed by TR-PCR. The transcripts were detectable at all the concentrations (20, 40, 60 microg/ml) of LPSs used. These results suggest that D. desulfuricans LPS may activate immune functions in endothelial cells and influence the inflammatory response during bacteremia caused by these bacteria.
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PMID:Desulfovibrio desulfuricans lipopolysaccharides induce endothelial cell IL-6 and IL-8 secretion and E-selectin and VCAM-1 expression. 1466 22

In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/ or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-gamma), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22-57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-gamma showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system.
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PMID:Infiltrating cells and related cytokines in lesional skin of patients with chronic idiopathic urticaria and positive autologous serum skin test. 1470 3

The recruitment of monocytes into the artery wall is a crucial early step in atherogenesis. A novel compound, KR-31378, has been shown to be a neuroprotective agent for ischemia-reperfusion damage in rat brain via its potent antioxidant and antiapoptotic actions. Here, we report the effects of this compound on atherogenesis and possible mechanisms of action. In Ldlr knockout mice fed with a high-fat, high-cholesterol diet, treatment with KR-31378 significantly inhibited fatty streak formation and macrophage accumulation. To address the possibility that KR-31378 may influence the initial stages of atherogenesis, we examined its effect on the adhesion and migration of monocytes to endothelial cells stimulated with tumor necrosis factor-alpha. KR-31378 decreased the adhesion in a dose-dependent manner. The observed decreases in cell adhesion and migration correlated with KR-31378-mediated down-regulation of vascular cell adhesion molecule-1 (VCAM-1) and interleukin (IL)-8. Nuclear factor-kappaB (NF-kappaB) is known to regulate the expression of adhesive and chemotactic molecules including VCAM-1 and IL-8. Indeed, transient transfection experiments, electrophoretic mobility shift assay, and IkappaB degradation assay showed that KR-31378 decreased NF-kappaB activation. These results indicate that KR-31378 potently reduces fatty streak formation by inhibiting NF-kappaB-dependent cellular adhesion and chemotactic molecule expression, which are crucial to monocyte infiltration into the arterial wall during the early stages of atherogenesis.
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PMID:KR-31378 ameliorates atherosclerosis by blocking monocyte recruitment in hypercholestrolemic mice. 1476 97


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