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

The synovium in rheumatoid arthritis (RA) is characterized by an increase in lining layer thickness and infiltration of inflammatory cells into the sublining area. Fibroblasts in the lining layer develop the appearance of "transformed cells", under the influence of proto-oncogenes involved in the regulation of the cell cycle. Fibroblast and macrophage-derived cytokines such as IL-1 and TNF-alpha are present abundantly in the rheumatoid synovium and stimulate these cells to produce destructive enzymes. Other cytokines such as IL-4 and IL-10 represent a physiological attempt to reverse the inflammatory process. Adhesion molecules facilitate both the migration of cells to the joint as well as the attachment of synovium to bone and cartilage. Joint destruction is mediated by enzymes such as serine proteases, matrix metalloproteinases (MMPs) and the cathepsins. Treatments directed against various components of the inflammatory cascade have shown promise. Inhibition of MMPs or adhesion molecules, blockade of IL-1 or TNF-alpha and the use of anti-Fas antibodies to induce apoptosis offer new possibilities for the treatment of RA. More recently, the employment of genes with antiarthritic properties has shown therapeutic potential.
 ...
PMID:Mechanism of joint destruction in rheumatoid arthritis. 951 Sep 39

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
 ...
PMID:Endothelial function and hemostasis. 1079 71

Adhesion molecules are important for cell trafficking and delivery of secondary signals for stimulation of T cells and antigen-presenting cells (APCs) in a variety of immune and inflammatory responses. Adhesion molecules lymphocyte function-associated antigen (LFA)-1 and CD2 on T cells recognize intercellular adhesion molecule (ICAM)-1 and LFA-3 on APCs, respectively. Recent studies have suggested that these molecules might play a regulatory role in antigen-specific immune responses. To investigate specific roles of adhesion molecules in immune induction we coimmunized LFA-3 and ICAM-1 cDNAs with a gD plasmid vaccine and then analyzed immune modulatory effects and protection against lethal herpes simplex virus (HSV)-2 challenge. We observed that gD-specific IgG production was enhanced by LFA-3 coinjection. However, little change in IgG production was observed by ICAM-1 coinjection. Furthermore, both Th1 and Th2 IgG isotype production was driven by LFA-3. LFA-3 also enhanced Th cell proliferative responses and production of interleukin (IL)-2, interferon-gamma, IL-4, and IL-10 from splenocytes. In contrast, ICAM-1 showed slightly increasing effects on T-cell proliferation responses and cytokine production. beta-Chemokine production (RANTES, MIP-1alpha, and MCP-1) was also influenced by LFA-3 or ICAM-1. When animals were challenged with a lethal dose of HSV-2, LFA-3-coimmunized animals exhibited an enhanced survival rate, as compared to animals given ICAM-1 or gD DNA vaccine alone. This enhanced protection appears to be mediated by CD4+ T cells, as determined by in vitro and in vivo T-cell subset deletion. These studies demonstrate that adhesion molecule LFA-3 can play an important role in generating protective antigen-specific immunity in the HSV model system through increased induction of CD4+ Th1 T-cell subset.
 ...
PMID:LFA-3 plasmid DNA enhances Ag-specific humoral- and cellular-mediated protective immunity against herpes simplex virus-2 in vivo: involvement of CD4+ T cells in protection. 1091 58

One of the major therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair following myocardial infarction. However, a sound understanding of the biology is necessary before a specific intervention is pursued on a therapeutic basis. This review summarizes our current understanding of the cellular and molecular mechanisms regulating the inflammatory response following myocardial ischemia and reperfusion. Myocardial necrosis induces complement activation and free radical generation, triggering a cytokine cascade initiated by Tumor Necrosis Factor (TNF)-alpha release. If reperfusion of the infarcted area is initiated, it is attended by an intense inflammatory reaction. Interleukin (IL)-8 synthesis and C5a activation have a crucial role in recruiting neutrophils in the ischemic and reperfused myocardium. Neutrophil infiltration is regulated through a complex sequence of molecular steps involving the selectins and the integrins, which mediate leukocyte rolling and adhesion to the endothelium. Marginated neutrophils exert potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. Despite this potential injury, substantial evidence suggests that reperfusion enhances cardiac repair improving patient survival; this effect may be in part related to the inflammatory response. Monocyte Chemoattractant Protein (MCP)-1 is also markedly upregulated in the infarcted myocardium inducing recruitment of mononuclear cells in the injured areas. Monocyte-derived macrophages and mast cells may produce cytokines and growth factors necessary for fibroblast proliferation and neovascularization, leading to effective repair and scar formation. At this stage expression of inhibitory cytokines such as IL-10 may have a role in suppressing the acute inflammatory response and in regulating extracellular matrix metabolism. Fibroblasts in the healing scar undergo phenotypic changes expressing smooth muscle cell markers. Our previous review in this journal focused almost exclusively on reduction of the inflammatory injury. The current update is prompted by the potential therapeutic opportunity that the open vessel offers. By promoting more effective tissue repair, it may be possible to reduce the deleterious remodeling, that is the leading cause of heart failure and death. Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction.
 ...
PMID:The inflammatory response in myocardial infarction. 1174 11

Adhesion molecules are important for leukocyte extravasation and for the delivery of costimulatory signals in T cell activation. We therefore interfered in the immune process leading to islet inflammation in diabetes prone NOD mice by oral vaccination with plasmid DNA encoding soluble ICAM-1. Female NOD mice were treated orally with ICAM-1, TGF-beta, or control plasmid DNA and received a single injection of cyclophosphamide for synchronization and acceleration of the disease process in the pancreas. Quantitative RT-PCR analysis of pancreatic mRNA showed that cyclophosphamide induced the expression of Th1 cytokines (IFN-gamma and IL-12p40) in vehicle- or control plasmid-treated mice. Treatment with ICAM-1 and TGF-beta DNA resulted in increased levels of IL-10 mRNA in the pancreas, indicating an anti-inflammatory regulatory immune response. Histological analysis of pancreatic islets showed that the DNA treatment did not alter islet infiltration in response to cyclophosphamide. Hence vaccination with the ICAM-1 plasmid had not suppressed leukocyte migration but rather modulated lymphocyte activity, similarly as seen for the TGF-beta-encoding plasmid. Neither of the three plasmids caused recognizable changes in cytokine expression in the small intestine, Peyer's patches, or mesenteric lymph nodes. We conclude that oral vaccination with DNA encoding immunoregulatory molecules such as ICAM-1 and TGF-beta represents an approach for modulating the ongoing inflammatory process in the pancreas of diabetes prone NOD mice.
 ...
PMID:Oral DNA vaccination with a plasmid encoding soluble ICAM-1 modulates cytokine expression profiles in nonobese diabetic mice. 1202 42

The present study aims at evaluating the role of protein kinase C (PKC) in the development of acute lung injury, production of inflammatory mediators and expression of adhesion molecules on leukocytes after induction of acute pancreatitis (AP). AP was induced by the intraductal infusion of 5% sodium taurodeoxycholate in the rat. The animals had the PKC inhibitor polymyxin B administered intraperitoneally 30min prior to induction of AP. Levels of protein content, protease activity, cytokines and chemokines in bronchoalveolar lavage fluid (BALF) were assessed 1 and 6h after AP induction. Adhesion molecule expression on leukocytes were measured by flowcytometry. Pretreatment with polymyxin B prevented against acute pancreatitis-induced lung injury and the otherwise occurring increases in TNF-alpha, IL-1beta, MCP-1 and IL-10, as well as against the decreases in IL-2, IFNgamma and TIMP-1, decreased protease activity and down-regulation of CD31, CD54 and CD62L on recruited neutrophils and macrophages in BALF. The results indicate that the leukocyte response in acute pancreatitis vary depending on leukocyte subpopulation. It seems that activation of the PKC signalling pathway may play an important role in pancreatitis-associated lung injury.
 ...
PMID:Protein kinase C modulates the pulmonary inflammatory response in acute pancreatitis. 1621 26

Lipoteichoic acid (LTA) is a major immunostimulatory molecule in the cell wall of Gram-positive bacteria. Adhesion of LTA to a polystyrene surface drastically increased its immunostimulatory potency in human whole blood in comparison to soluble LTA, although only 1% of the LTA had bound, as determined using rhodamine-labelled LTA. The release of the proinflammatory cytokines IL-1beta, TNF and IL-6 and the chemokines IL-8 and G-CSF was increased 2- to 10-fold, but IL-10 release was unaltered. This presentation effect was not shared by lipopolysaccharide (LPS) or other toll-like receptor 2 agonists and was less pronounced in polypropylene vessels. LTA did not induce cytokine release in silicone-coated borosilicate vessels, but covalent coupling of LTA to polystyrene beads restored cytokine induction in these vessels, indicating that presentation of LTA on a surface is in fact essential for its immunostimulatory potency. This novel aspect of presentation as a factor in the recognition of LTA may reflect the physiological situation in the bacterial cell wall, where LTA is anchored in the bacterial membrane and projects through the peptidoglycan. In practical terms, contamination of medical devices with components of Gram-positive bacteria may pose an underestimated inflammatory risk.
 ...
PMID:Presentation of lipoteichoic acid potentiates its inflammatory activity. 1851 54

In this study, we analyzed the probiotic potential of L. plantarum DSMZ 12028 in vitro using the pathogen E. coli K4 and a certified probiotic, L. paracasei F19, as controls. Adhesion to intestinal epithelial cells was evaluated using two cell lines, CaCo-2 and HT-29, through the plate dilution method. Moreover, the bacteria/epithelial dynamic interaction was continuously monitored using time-lapse microscopy. Expression of the innate immunity receptors, the TLRs, was evaluated by semi-quantitative PCR on an epithelial/bacteria co-culture. Real-time PCR was used to monitor expression of TLRs and cytokines in a monocytic cell line (THP-1) following bacterial exposure. The adherence of the strain to intestinal epithelial cells was comparable to that of the probiotic. Time-lapse experiments showed that E. coli K4 induced cell death while L. plantarum did not affect proliferation at a 10:1 bacteria/cell ratio. L. plantarum down-regulated TLR mRNAs with the exception of TLR2, while L. paracasei F19 and E. coli K4 caused a significant (p<0.05) up-regulation of TLR2 and 4, respectively. To simulate the activation of underlying immune cells in the lamina propria, we analyzed the immunomodulation of L. plantarum on a monocytic cell line, THP-1. Proinflammatory cytokines, such as TNFalpha, were increased by the presence of bacteria. The pathogen E. coli K4 also induced a strong up-regulation of proinflammatory cytokines, such as IL8, IL1beta and IL23. No differences were observed between experimental groups for IFNgamma, IL-10 and IL12p40. Overall, L. plantarum DSMZ 12028 demonstrated probiotic traits, inducing a proinflammatory response just above the "threshold level", which could prevent an inflammatory outcome, while inducing a higher state of alertness in the defense system of the host intestinal epithelial cells.
 ...
PMID:In vitro evaluation of Lactobacillus plantarum DSMZ 12028 as a probiotic: emphasis on innate immunity. 1974 96

Body mass index (BMI), serum cytokines and serum obesity markers were evaluated in 33 obese children before, during and after a hypocaloric diet. The cytometric bead array "human inflammatory kit" was used for the evaluation of serum interleukin (IL)-1beta, IL-6, IL-10 and tumor necrosis factor-alpha. On the other hand, the following obesity biomarkers were evaluated by means of a flowcytomix-human obesity 9 plex kit: Soluble Isoform of CD40 Ligand; Soluble Intercellular Adhesion Molecule-1; Leptin; Monocyte Chemoattractant Protein 1; Myeloperoxidase; Osteoprotegerin; Resistin and Soluble TNF-receptors. Actually, throughout the study modifications of BMI were negligible and, therefore, serum cytokines and obesity markers did not show any significant changes in comparison with baseline values. On the other hand, at the different time points considered the majority of obesity markers were higher than normal controls, thus indicating a low grade inflammation in childhood obesity. Therefore, attempts at reducing this inflammatory status in children which predisposes to the metabolic syndrome outcome are discussed.
 ...
PMID:Effects of a hypocaloric diet on obesity biomarkers: prevention of low-grade inflammation since childhood. 2038 3

Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) deficient mice in the FVB/n strain exhibit fatal chronic pulmonary fibrotic disease. The illness occurs in the absence of a detectable pro-inflammatory event. PECAM-1 is vital to the stability of vascular permeability, leukocyte extravasation, clotting of platelets, and clearance of apoptotic cells. We show here that the spontaneous development of fibrotic disease in PECAM-1 deficient FVB/n mice is characterized by early loss of vascular integrity in pulmonary capillaries, resulting in spontaneous microbleeds. Hemosiderin-positive macrophages were found in interstitial spaces and bronchoalveolar lavage (BAL) fluid in relatively healthy animals. We also observed a gradually increasing presence of hemosiderin-positive macrophages and fibrin deposition in the advanced stages of disease, corresponding to the accumulation of collagen, IL-10 expression, and myofibroblasts expressing alpha smooth muscle actin (SMA). Together with the growing evidence that pulmonary microbleeds and coagulation play an active part in human pulmonary fibrosis, this data further supports our hypothesis that PECAM-1 expression is necessary for vascular barrier function control and regulation of homeostasis specifically, in the pulmonary environment.
...
PMID:Microhemorrhage is an early event in the pulmonary fibrotic disease of PECAM-1 deficient FVB/n mice. 2497 47


1 2 Next >>