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Endothelial Adhesion Molecules (endothelial + adhesion_molecule)
Selected AbstractsEffects of TNF-alpha antagonism on E-selectin in obese subjects with metabolic dysregulationCLINICAL ENDOCRINOLOGY, Issue 1 2010Markella V. Zanni Summary Objective, Endothelial adhesion molecules like E-selectin play an important role in leukocyte recruitment and development of atherosclerotic plaque. E-selectin is increased in obesity, yet little is known regarding the specific factors contributing to elevated E-selectin in obesity and whether tumour necrosis factor alpha (TNF-alpha) increases E-selectin in vivo in this population. The objectives of this study were to: (1) determine the body composition, metabolic and inflammatory factors associated with increased E-selectin and (2) determine the role of TNF-alpha in the physiological regulation of E-selectin by antagonism of TNF-alpha with etanercept among obese subjects. Methods, E-selectin levels, body composition, metabolic parameters and inflammatory cytokines were assessed in 51 obese subjects and 37 non-obese healthy controls. Obese subjects were randomized to etanercept 50 mg weekly or placebo for 4 weeks. Changes in E-selectin were compared between treatment groups. Results, Obese subjects had higher E-selectin than non-obese controls (47·4 [32·7,58·8] vs. 27·2 [20·3,42·1] ng/ml, obese vs. non-obese, P < 0·0001). E-selectin was significantly associated with multiple body composition measures and metabolic parameters, along with specific measures of TNF-alpha activation, including soluble tumour necrosis factor receptors 1 (P = 0·03) and 2 (P = 0·02). In multivariate modelling, visceral adipose tissue, but not other measures of body composition, remained significantly associated with E-selectin. Among obese subjects, treatment with etanercept significantly decreased E-selectin (,5·7 ± 8·7 vs. 0·5 ± 6·0 ng/ml, etanercept vs. placebo, P = 0·005). Conclusions, E-selectin is increased in obesity, in relationship to increased visceral adiposity and markers of TNF-alpha activation. TNF-alpha antagonism with etanercept reduces E-selectin in obese subjects, providing evidence that the systemic circulatory release of E-selectin is regulated at least in part by TNF-alpha in obesity. [source] Effect of intravenous lidocaine administration on laminar inflammation in the black walnut extract model of laminitisEQUINE VETERINARY JOURNAL, Issue 3 2010J. M. WILLIAMS Summary Reasons for performing study: Laminitis is a serious complication of horses suffering from sepsis/endotoxaemia-related events. Laminitis in horses and organ injury in human sepsis are both reported to involve inflammatory injury to the laminae/organs including early activation of endothelium and leucocytes leading to emigration of neutrophils into the tissue interstitium. In the black walnut extract (BWE) model, systemic inflammatory events coincide with marked increase in laminar mRNA concentrations of inflammatory genes including proinflammatory cytokines (i.e. IL-1,, IL-6), COX-2, chemokines (i.e. IL-8) and endothelial adhesion molecules (i.e. ICAM-1 and E-selectin). In models of human sepsis, i.v. lidocaine has been reported to decrease leucocyte and endothelial activation, and the expression of proinflammatory cytokines and chemokines. Objectives: To evaluate the effect of i.v. lidocaine therapy on the inflammatory processes documented to occur in the BWE model of laminitis. Methods: Twelve horses were administered BWE and treated immediately with either lidocaine (1.3 mg/kg bwt bolus, followed by 0.05 mg/kg bwt/min CRI, n = 6) or saline (n = 6) for 10 h. At 10 h post BWE administration, laminar samples were obtained under general anaesthesia for assessment of proinflammatory gene expression (using RT-qPCR) and leucocyte emigration (via CD13 immunohistochemistry). At 0, 3 and 10 h post BWE administration, skin samples were obtained for assessment of leucocyte emigration (via calprotectin immunohistochemistry). Results: No significant differences between groups were noted for inflammatory gene mRNA concentrations (IL-1,, IL-6, IL-8, COX-2) or for number of leucocytes present within the laminar interstitium or skin dermis. Increased (P<0.05) laminar E-selectin mRNA concentrations were present in the LD group (vs. SAL group). Conclusions: Continuous administration of i.v. lidocaine does not inhibit inflammatory events in either the laminae or skin in the horse administered black walnut extract. Potential relevance: This work questions the use of continuous i.v. administration of lidocaine as an effective anti-inflammatory therapy for systemic inflammation. [source] Down-regulation of endothelial adhesion molecules and leukocyte adhesion by treatment with superoxide dismutase is beneficial in chronic immune experimental colitisINFLAMMATORY BOWEL DISEASES, Issue 10 2005Joaquim Seguí PhD Abstract Modulation of adhesion molecule expression that govern trafficking of leukocytes into the inflamed intestine is envisioned as a new strategy for treatment of inflammatory bowel disease (IBD). This study was designed to determine the impact of reducing oxidative stress on adhesion molecules expression and leukocyte recruitment in experimental chronic colitis. For that purpose, colitic interleukin-10 knockout and wild-type mice were studied. Groups of animals were treated with Cu/Zn superoxide dismutase (SOD1) 13 mg/kg/d or vehicle for either 7 or 14 days. Expression of vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1 were determined; leukocyte-endothelial cell interactions in colonic venules were studied with intravital microscopy; and changes in colon pathology and biomarkers of colitis severity were determined. Development of colitis was associated with a marked increase in endothelial vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1 expression, which were significantly reduced by treatment with SOD1. The increase in leukocyte rolling and adhesion in colonic venules of colitic mice were significantly reduced by administration of SOD1. This treatment markedly reduced colonic lipid hydroperoxidation, myeoloperoxidase activity, and plasma levels of serum amyloid A protein and resulted in significant, although modest, reductions in histologic damage score. The therapeutic value of SOD1 when administered prophylactically was assessed in the dextran sulfate sodium model of colitis with similar positive results. These results indicate that SOD1 affords significant amelioration of colonic inflammatory changes in experimental colitis. Down-regulation of adhesion molecule expression, reduction of lipid hydroperoxidation, and recruitment of leukocytes into the inflamed intestine contribute to this beneficial effect. [source] Acute inflammatory reactions caused by histamine via monocytes/macrophages chronically participate in the initiation and progression of atherosclerosisPATHOLOGY INTERNATIONAL, Issue 7 2004Satoshi Kimura Previously we demonstrated that histidine decarboxylase (HDC), which produces histamine from l -histidine, was detected in monocytes/macrophages located in human atherosclerotic lesions. As monocytic migration is a key event of atherogenesis, we investigated whether histamine induces monocytic expression of monocyte chemoattractant protein (MCP)-1 and its receptors CCR2-A and -B, and also endothelial expression of ICAM-1 and VCAM-1. Furthermore, we studied the effect of interleukin (IL)-4, which inhibits the HDC expression, on the expression of MCP-1 and CCR2. Histamine stimulated monocytes, but not macrophages, to express MCP-1 and CCR2-A and -B. The expression of MCP-1 was inhibited by histamine H2 blocker. In contrast, IL-4 enhanced CCR2 expression but not MCP-1. Histamine stimulated endothelial cells to express ICAM-1 and VCAM-1. These results indicate that histamine and IL-4, which are both synthesized in the arterial intima, chronically participates in the pathogenesis of atherosclerosis via the enhanced expression of monocytic MCP-1, CCR2 and endothelial adhesion molecules. [source] | ||||||||||