Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Members of the interleukin (IL)-12 family constitute subunits of IL-12, -23, and -27. These ILs represent pivotal mediators in the regulation of cell-mediated immune responses and in animal models of human inflammatory bowel disease. Recent work has suggested that intestinal endothelial cells might serve as a second line of defense in bacterial sensing of invading pathogens. The purpose of this study was to examine the production of IL-12 family members in intestinal endothelial cells (HIMEC). HIMEC were stimulated with proinflammatory agents (TNF-alpha, IFN-gamma, IL-1beta) and microbial antigens [LPS, lipoteichoic acid, peptidoglycan, CpG-DNA, flagellin, poly(I:C)]. Expression of IL-12 family members and of Toll-like receptor (TLR)3 in HIMEC was assessed by real-time RT-PCR, immunostaining, flow cytometry, and immunoblot analysis. HIMEC display an induction of Epstein-Barr virus-induced gene 3 (EBI3), IL-12p35, and IL-23p19, whereas no expression of IL-12p40 and IL-27p28 was detectable. The strongest induction was induced by proinflammatory factors known to utilize the NF-kappaB pathway, and expression of EBI3 and IL-23p19 was diminished by an NF-kappaB inhibitor. HIMEC display regulated expression of TLR3. Adhesion and transmigration assays showed proinflammatory responses after HIMEC stimulation. HIMEC are capable of producing IL-12 family members as a response to microbial stimuli. The TLR3 agonist, poly(I:C), was shown to enhance leukocyte adhesion in vitro in HIMEC. Our data suggest that the intestinal microvasculature is responsive to ligands of TLR3 expressed on intestinal endothelial cells, thereby adding to the regulation of adaptive immunity and leukocyte recruitment.
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PMID:Expression of IL-12-related molecules in human intestinal microvascular endothelial cells is regulated by TLR3. 1794 55

Adhesion molecules expressed by activated endothelial cells play a key role in regulating leukocyte trafficking to sites of inflammation. Resting endothelial cells normally do not express adhesion molecules, but cytokines activate endothelial cells to express adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1), which mediate leukocyte adherence to endothelial cells. We now show that endothelial cells express microRNA 126 (miR-126), which inhibits VCAM-1 expression. Transfection of endothelial cells with an oligonucleotide that decreases miR-126 permits an increase in TNF-alpha-stimulated VCAM-1 expression. Conversely, overexpression of the precursor to miR-126 increases miR-126 levels and decreases VCAM-1 expression. Additionally, decreasing endogenous miR-126 levels increases leukocyte adherence to endothelial cells. These data suggest that microRNA can regulate adhesion molecule expression and may provide additional control of vascular inflammation.
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PMID:MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. 1822 15

Mesenchymal stem cells (MSCs) participate in the wound healing process in mammalians. Adhesion of MSCs to endothelium is a key step in the homing of MSCs circulating in the bloodstream to the sites of injury and inflammation. Because endothelial cells (ECs) may become apoptotic under certain pro-inflammatory conditions, we investigated the effects of pro-inflammatory, TNF-alpha and IL-1 beta, and pro-apoptotic agents, actinomycin D, cycloheximide, okadaic acid, wortmannin, and staurosporine, on human MSCs (hMSCs) adhesion to ECs. Treatment of ECs with pro-apoptotic agents markedly increased adhesion of hMSCs to ECs. This adhesion correlated with reduction of mitochondrial membrane potential, inhibition of NADH dehydrogenases, and release of von Willebrand factor (vWF) by ECs. Treatment of ECs with exogenous vWF also stimulated hMSC adhesion. These data provide evidence that apoptosis of ECs may regulate homing of hMSCs to the sites of tissue injury. These results are consistent with the hypothesis that activation of apoptotic signaling pathways in ECs releases vWF which regulates hMSC adhesion to ECs.
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PMID:Apoptotic endothelial cells demonstrate increased adhesiveness for human mesenchymal stem cells. 1902 68

Lymphocyte recruitment is a key pathogenic event in inflammatory bowel disease (IBD). Adhesion of T cells to human intestinal microvascular endothelial cells (HIMEC) is mediated by ICAM-1, VCAM-1 and fractalkine (FKN), but the signaling molecules that orchestrate this process have yet to be identified. Because MAPK play an important role in the response of many cell types to pro-inflammatory stimuli, we assessed the functional role of p38 MAPK, p42/44 MAPK and JNK in the regulation of lymphocyte adhesion to and chemotaxis across the microvasculature in IBD. We found that the MAPK were phosphorylated in the bowel microvasculature and human intestinal fibroblasts of patients with IBD but not of healthy individuals. Stimulation of HIMEC with TNF-alpha triggered phosphorylation of the MAPK, and up-regulation of VCAM-1, FKN and ICAM-1. Blockade of p38 decreased the expression of all MAPK by 50% (p<0.01), whereas inhibition of p42/44 decreased the expression of ICAM-1 and FKN by 50% (p<0.01). Treatment of human intestinal fibroblasts with TNF-alpha elicited production of IL-8 and MCP-1, which was reduced (p<0.05) by blockade of p38 and p42/44. Finally, blockade of p38 and p42/44 reduced lymphocyte adhesion to (p<0.05) and transmigration across (p<0.05) HIMEC monolayers. These findings suggest a critical role for MAPK in governing lymphocyte influx into the gut in IBD patients, and their blockade may offer a molecular target for blockade of leukocyte recruitment to the intestine.
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PMID:The role of MAPK in governing lymphocyte adhesion to and migration across the microvasculature in inflammatory bowel disease. 1913 May 54

Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality. Increased expression of cell adhesion molecules (CAM) and their ligands mediate essential processes in atherogenesis. Niacin reduces atherosclerotic cardiovascular complications and total mortality. Further understanding is needed on effects of niacin on CAM, and its functional consequences. The aim of this study was to evaluate the effects of niacin on CAM expression and monocyte adhesion in endothelial cells. Endothelial cells (HUVEC) were cultured to reach 80-90% confluence before experiments were initiated. Cells were exposed to DME/F12 with selected concentrations of niacin. To elicit the expression of CAM, cells were stimulated by addition of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 or interferon-gamma. Lysate from the conditioned media was assayed for CAM. The effect of niacin on mRNA expression of ICAM-1 was studied using semi-quantitative analysis of ICAM-1 mRNA. Adhesion assays were performed with flow cytometry to study the functional significance of the effects niacin on CAM expression. Niacin significantly reduced ICAM-1 and PECAM-1 protein levels basally, and reduced the cytokine-induced rise in ICAM-1, with a similar effect for TNF-alpha-induced PECAM-1 rise. The decrease in TNF-alpha-induced rise in ICAM-1 level was associated with a reduction of NF-kappaB activation, a reduction in mRNA expression of ICAM-1, and a functional reduction in monocyte adhesion to cultured endothelial cells. Niacin reduces CAM expression and monocyte adhesion to endothelial cells. Apart from its lipid-modifying effects, these pleiotropic effects of niacin may potentially contribute to the beneficial effects of risk reduction for atherosclerotic disease.
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PMID:Effects of niacin on cell adhesion and early atherogenesis: biochemical and functional findings in endothelial cells. 1915 36

Chios mastic gum (CMG) is a white, semitransparent, natural resin that is obtained as a trunk exudate from mastic trees. Triterpenic compounds and phytosterols like tirucallol are among its major components. CMG has been associated with cardiovascular protection, exerting its effect mainly through increasing the antioxidant defense system, and effectively lowering the levels of serum cholesterol in human subjects. However, data on its anti-inflammatory effect on endothelium are scarce. Attachment of leukocytes to the vascular endothelium and the subsequent migration of cells into the vessel wall are early events in atherogenesis, and this process requires the expression of endothelial adhesion molecules. In this study, we examined the effect of CMG neutral extract (25-200 microg/ml) and tirucallol (0.1-100 microM) on the following: 1) the expression of adhesion molecules (VCAM-1 and ICAM-1) by Cell ELISA and 2) the attachment of monocytes (U937 cells) in TNF-alpha stimulated Human Aortic Endothelial Cells (HAEC) by Adhesion assay. The impact of treatment with CMG neutral extract and tirucallol in NFkB phosphorylation was also examined by a cell-based ELISA kit. Both CMG extract and tirucallol inhibit significantly VCAM-1 and ICAM-1 expression in TNF-alpha-stimulated HAEC. They also inhibit significantly the binding of U937 cells to TNF-alpha-stimulated HAEC and attenuate the phosphorylation of NFkB p65. This study extends existing data regarding the cardioprotective effect of CMG, expands the spectrum of known phytosterols with potent antiatheromatic activity, provides new insight into the mechanisms underlying the beneficial effect of CMG on endothelial function, and may aid in design of new therapy for intervention in atherosclerosis.
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PMID:Chios mastic gum extract and isolated phytosterol tirucallol exhibit anti-inflammatory activity in human aortic endothelial cells. 1923 52

P. marneffei is a thermal dimorphic fungus which causes penicilliosis, an opportunistic infection in immunocompromised patients in South and Southeast Asia. Little is known about the innate immune response to P. marneffei infection. Therefore, the initial response of macrophages to P. marneffei conidia was evaluated by us. Adhesion between monocytes from healthy humans and fungal conidia was examined and found to be specifically inhibited by MAbs against PRR, such as MR, (TLR)1, TLR2, TLR4, TLR6, CD14, CD11a, CD11b, and CD18. To study the consequences of these interactions, cytokines were also examined by ELISA. Binding of P. marneffei conidia to monocytes was significantly inhibited, in a dose-dependent manner, by MAbs against MR, TLR1, TLR2, TLR4, TLR6, CD14, CD11b and CD18. When monocytes were co-cultured with the conidia, there was an increase in the amount of surface CD40 and CD86 expression, together with TNF-alpha and IL-1beta production, compared to unstimulated controls. In assays containing anti-TLR4 or anti-CD14 antibody, reduction in the amount of TNF-alpha released by monocytes stimulated with P. marneffei conidia was detected. In addition, it was found that production of TNF-alpha and IL-1beta from adherent peripheral blood monocytes was partially impaired when heat-inactivated autologous serum, in place of untreated autologous serum, was added to the assay. These results demonstrate that various PRR on human monocytes participate in the initial recognition of P. marneffei conidia, and the engagement of PRR could partly initiate proinflammatory cytokine production.
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PMID:Engagement of Penicillium marneffei conidia with multiple pattern recognition receptors on human monocytes. 1930 27

Focal Adhesion Kinase (FAK) is implicated in a wide array of cellular processes and also involved in the production of matrix metalloproteinases (MMPs) which degrade extracellular matrix (ECM). We have shown that FAK plays a critical role in MMP-9 production and subsequent invasion of the cholangiocarcinoma activated by an inflammatory cytokine, TNF-alpha. By nature, cholangiocarcinoma is frequently associated with hepatolithiasis that causes recurrent inflammation. As degradation of the ECM is a prerequisite step for the invasion and metastasis of cancer cells, we used an assay of gelatin-degrading MMPs by Zymography to clarify the characteristic feature of the matrix degrading systems of the cancer cells. Immunoprecipitation and western blot analysis together with site specific phosphorylated FAK antibodies showed aberrant FAK activity in inflammation-mediated tumor cells. Confocal immunofluorescence staining could confirm not only localization but also phosphotyrosine contents of phosphorylated FAK by TNF-alpha stimulation. Destruction or penetration of the basement membrane is thought to be an essential step in successful metastasis by tumor cells, we used a matrix of basement membrane which was reconstituted on to a filter in the Boyden Chamber and assayed the ability of cancer cells to penetrate through matrigel-coated filter. We demonstrated the effectiveness of FAK siRNA treatment to prevent tumor invasion. Our observations suggested the importance of FAK as a therapeutic target for malignant neoplasm.
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PMID:Inflammation and tumor progression: a lesson from TNF-alpha-dependent FAK signaling in cholangiocarcinoma. 1934 83

Because changes in subendothelial matrix composition are associated with alterations of the endothelial immune phenotype, we sought to understand if cytokine-induced NF-kappaB activity and downstream effects depend on substrate adherence of endothelial cells (EC). We compared the upstream phosphorylation cascade, activation of NF-kappaB, and expression/secretion of downstream effects of EC grown on tissue culture polystyrene plates (TCPS) with EC embedded within collagen-based matrices (MEEC). Adhesion of natural killer (NK) cells was quantified in vitro and in vivo. NF-kappaB subunit p65 nuclear levels were significantly lower and p50 significantly higher in cytokine-stimulated MEEC than in EC-TCPS. Despite similar surface expression of TNF-alpha receptors, MEEC had significantly decreased secretion and expression of IL-6, IL-8, MCP-1, VCAM-1, and ICAM-1. Attenuated fractalkine expression and secretion in MEEC (two to threefold lower than in EC-TCPS; p < 0.0002) correlated with 3.7-fold lower NK cell adhesion to EC (6,335 +/- 420 vs. 1,735 +/- 135 cpm; p < 0.0002). Furthermore, NK cell infiltration into sites of EC implantation in vivo was significantly reduced when EC were embedded within matrix. Matrix embedding enables control of EC substratum interaction. This in turn regulates chemokine and surface molecule expression and secretion, in particular of those compounds within NF-kappaB pathways, chemoattraction of NK cells, local inflammation, and tissue repair.
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PMID:NF-kappaB activity in endothelial cells is modulated by cell substratum interactions and influences chemokine-mediated adhesion of natural killer cells. 1955 75

Genetic resistance to malaria is associated with various genetic factors, including erythrocytic variability and variability of the genes involved into the pathogenetic process. Some genetic anomalies resulted from selective malaria pressure, which brought into existence different forms of hemoglobinopathies, glucose-6-phosphate dehydrogenase deficiency, and no Duffy antigens, and ovalocytosis, etc., which ensured varying malaria resistance. Cell adhesion is a major factor in the pathogenesis of malaria. Adhesion molecules express on the cellular membranes of the endothelium, platelets, macrophages, red blood cells and serve as binding receptors for membrane proteins PFRMP-1 of P. falciparum. Polymorphism of the CD36, ICAM-1, and PECAM1 genes can lower binding to blood vessel endothelial cells, which reduces the number of clinical forms of malaria. The high serum TNF-alpha level that is caused by mutation in the promoter of the TNF-alpha gene is associated with cerebral malaria. TNF-alpha enhances the endothelial expression of adhesion molecules, by increasing the adhesion of infected erythrocytes, including that in cerebral capillaries, by inducing in patients local thrombosis and inflammation with release of the cytokines--TNF-alpha. The products of inflammatory infiltrates attack the endothelium, by leading to the imbibition of plasma and erythrocytes in brain tissue and causing a cerebral form of malaria.
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PMID:[Genetic resistance to malaria]. 1956 55


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