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)

Adhesions of leukocytes to hepatocytes and sinusoidal endothelial cells mediates the induction and progression of hepatic injury. However, in contrast to endothelial cells, information regarding the regulation of interactions between leukocytes and hepatocytes is limited. In the present study, we investigated the effect of inflammatory mediators including lipopolysaccharide (LPS), staphylococcal enterotoxin B (SEB), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) on the adhesion of polymorphonuclear leukocytes or lymphocytes to primary cultured rat hepatocytes, and on the expression of intercellular adhesion molecule-1 (ICAM-1) gene in hepatocytes. Both polymorphonuclear leukocyte and lymphocyte adhesion to hepatocytes were enhanced after exposure of hepatocytes to IFN-gamma and TNF-alpha, but not after exposure to LPS, SEB or IL-1beta. The adhesion induced by either IFN-gamma or TNF-alpha was inhibited by monoclonal antibodies against ICAM-1 or lymphocyte function-associated antigen-1 (LFA-1). Nonstimulated hepatocytes expressed faintly ICAM-1 mRNA, which increased slightly during the culture period. ICAM-1 mRNA expression was up-regulated to a greater extent by incubating hepatocytes with IFN-gamma or TNF-alpha, and peaked after 12 hr of incubation with TNF-alpha and after 24 hr with IFN-gamma. These results indicate that IFN-gamma and TNF-alpha induce the expression of ICAM-1 on parenchymal hepatocytes and that the LFA-1-ICAM-1 pathway plays an important role in the interaction between hepatocytes and neutrophils or lymphocytes.
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PMID:Effects of cytokines on the binding of leukocytes to cultured rat hepatocytes and on the expression of ICAM-1 by hepatocytes. 1021 41

Interleukin-10 (IL-10) is an anti-inflammatory helper T cell type 2 (Th2) cytokine that modulates Th1-type cytokine production. Graft arterial disease (GAD) is a vascular obliterative process mediated via the Th1 cytokine interferon-gamma (IFN-gamma); allografts in IFN-gamma-deficient animals do not develop GAD. We investigated the effect of IL-10 and anti-IL-10 on GAD in murine heart transplants and whether anti-IL-10 reestablishes GAD in IFN-gamma-deficient hosts. Major histocompatibility complex class II-mismatched hearts were transplanted for 8 weeks into wild-type or IFN-gamma-deficient mice. In one set of experiments, wild-type hosts received daily administration of phosphate-buffered saline (PBS) or increasing IL-10; in a subsequent set of experiments, wild-type hosts received weekly PBS, rat IgG, or anti-IL-10 monoclonal antibody; IFN-gamma-deficient recipients received weekly PBS or anti-IL-10 monoclonal antibody. Explanted allografts were assessed for parenchymal rejection and GAD, cytokine profiles, and adhesion/costimulatory-molecule expression. Exogenous IL-10 resulted in increased Th2-like cytokine production; nevertheless, it exacerbated parenchymal rejection and GAD and increased CD8(+) infiltration. Anti-IL-10 did not significantly affect the extent of rejection or GAD, cytokine profiles, or immunohistology of the allografts in wild-type hosts. Adhesion molecule (CD54 and CD106) expression was not diminished by IL-10 treatment, and costimulatory-molecule (CD80 and CD86) expression was augmented by administration of exogenous IL-10. Allografts in IFN-gamma-deficient recipients showed mild rejection and no GAD, regardless of anti-IL-10 treatment. IL-10 in vivo thus has markedly different effects than predicted from in vitro experience. Although allografts develop Th2-like cytokine profiles treatment with IL-10 causes exacerbated rejection and GAD.
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PMID:Interleukin-10 (IL-10) augments allograft arterial disease: paradoxical effects of IL-10 in vivo. 1059 23

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.
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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

The production of nitric oxide (NO) within neutrophils is an important element of the innate immune response. We have previously shown that cytokines (IL-1alpha, tumour necrosis factor-alpha and interferon-gamma) induce human neutrophils in buffy coat preparations to produce iNOS. In order to define better the exact requirements for iNOS production within human neutrophils, we have studied the conditions needed for the production of iNOS in purified neutrophils. In contrast to buffy coat preparations, purified neutrophils in suspension did not produce an increase in iNOS following addition of cytokines. However, when purified neutrophils were allowed to adhere to glass surfaces either uncoated or coated with fetal calf serum (FCS), plasma, fibronectin or laminin, there was an increase in the percentage of iNOS-positive cells. The addition of cytokines during adhesion of these cells increased this proportion further. This was most marked for glass alone and FCS-coated glass on which the proportion of iNOS-positive cells increased to 22.7% and 35.5%, respectively, a significant increase compared with cytokine-treated neutrophils in suspension. Neither transmigration through activated endothelial monolayers nor the addition of soluble intercellular adhesion molecule-1 to purified neutrophil suspensions increased the percentage of iNOS-positive cells following cytokine stimulation. Adhesion of neutrophils to surfaces coated with IgG or complement also failed to increase cytokine-induced iNOS production. We conclude that iNOS production in human neutrophils requires not only cytokine stimulation, but also additional stimuli from adhesion to a surface.
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PMID:Effect of adhesion on inducible nitric oxide synthase (iNOS) production in purified human neutrophils. 1116 96

A common intracellular signal activating polymorphonuclear leukocytes (PMN) in inflammation is a change in cytosolic calcium concentration. Previously, we have shown that interferon-gamma (IFN-gamma) induces transient calcium signals in PMN, but only after intracellular calcium store depletion. Using a digital imaging system, we show that adhesion of PMN is critical for IFN-gamma-induced calcium signals, and with PMN attached to the optimal coating, the calcium signals are evoked even in presence of extracellular calcium, that is, non-depleted calcium stores. Adhesion to fibronectin, pure or extracted from plasma by gelatin, improved the IFN-gamma responses compared with serum, plasma, or vitronectin coats. In accordance with previous observations, IFN-gamma-induced calcium signals in fibronectin adherent cells were totally abolished by the G-protein inhibitor pertussis toxin and were also inhibited by the sphingosine kinase inhibitors dimethylsphingosine (DMS) and N-acetylsphingosine (N-Ac-Sp). PMN contact with fibronectin alone, measured in cells sedimenting onto a fibronectin-coated surface or by addition of fibronectin to glass-adherent cells, evoked transient calcium signals. However, PMN in suspension did not respond to the addition of fibronectin or arginine-glycine-aspartate (RGD). The fibronectin-induced calcium signals were also clearly depressed by pertussis toxin and by the sphingosine kinase inhibitors DMS, dihydrosphingosine (DHS), and N-Ac-Sp. When the product of sphingosine kinase activity, sphingosine 1-phosphate (S1-P), was added to the cells, similar calcium signals were induced, which were dependent on a pertussis toxin-sensitive G-protein activity. Finally, addition of S1-P to the cells prior to stimulation with IFN-gamma partly mimicked the priming effect of fibronectin. In conclusion, fibronectin contact evokes by itself a calcium signal in PMN and further promotes calcium signaling by IFN-gamma. We suggest that fibronectin might activate sphingosine kinase, and that the sphingosine 1-phosphate thereby generated induces a calcium signal via a G-protein-dependent mechanism. Apparently, sphingosine kinase activity is also involved in IFN-gamma induced calcium signals.
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PMID:Fibronectin promotes calcium signaling by interferon-gamma in human neutrophils via G-protein and sphingosine kinase-dependent mechanisms. 1193 87

Amphoterin (HMGB1) is a 30-kD heparin-binding protein involved in process extension and migration of cells by a mechanism involving the receptor for advanced glycation end products (RAGE). High levels of amphoterin are released to serum during septic shock. We have studied the expression of amphoterin in monocytes and the role of amphoterin and RAGE in monocyte transendothelial migration. Un-activated monocytes in suspension did not reveal amphoterin on their surface, but adherent monocytes exported amphoterin to the cell surface. Immunohistochemical staining of arterial thrombi in vivo revealed amphoterin in mononuclear cells and in surrounding extracellular matrix. Amphoterin was secreted from phorbol ester and interferon-gamma (IFN-gamma)-activated macrophages, and the secretion was inhibited by blocking the adenosine 5'-triphosphate (ATP)-binding cassette transporter-1, a member of the multidrug resistance protein family. Amphoterin was specifically adhesive for monocytes in peripheral blood leukocyte adhesion assay. Adhesion caused an extensive spreading of cells, which was inhibited by the dominant-negative RAGE receptor (soluble ectodomain of RAGE), and adhesion up-regulated chromogranin expression in monocytes, also suggesting a RAGE-dependent interaction. Monocyte transendothelial migration was efficiently inhibited by anti-amphoterin and anti-RAGE antibodies and by the soluble RAGE. We suggest that amphoterin is an autocrine/paracrine regulator of monocyte invasion through the endothelium.
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PMID:Regulation of monocyte migration by amphoterin (HMGB1). 1513 Sep 41

Chronic periaortitis (CP) is an uncommon inflammatory disease which primarily involves the infrarenal portion of the abdominal aorta. However, CP should be regarded as a generalized disease with three different pathophysiological entities, namely idiopathic retroperitoneal fibrosis (RPF), inflammatory abdominal aortic aneurysm and perianeurysmal RPF. These entities share similar histopathological characteristics and finally will lead to fibrosis of the retroperitoneal space. Beside fibrosis, an infiltrate with variable chronic inflammatory cell is present. The majority of these cells are lymphocytes and macrophages as well as vascular endothelial cells, most of which are HLA-DR-positive. B and T cells are present with a majority of T cells of the T-helper phenotype. Cytokine gene expression analysis shows the presence of interleukin (IL)-1alpha, IL-2, IL-4, interferon-gamma and IL-2 receptors. Adhesion molecules such as E-selectin, intercellular adhesion molecule-1 and the vascular cell adhesion molecule-1 were also found in aortic tissue, and may play a significant role in CP pathophysiology. Although CP pathogenesis remains unknown, an exaggerated inflammatory response to advanced atherosclerosis (ATS) has been postulated to be the main process. Autoimmunity has also been proposed as a contributing factor based on immunohistochemical studies. The suspected allergen may be a component of ceroid, which is elaborated within the atheroma. We review the pathogenesis and the pathophysiology of CP, and its potential links with ATS. Clinically relevant issues are summarized in each section with regard to the current working hypothesis of this complex inflammatory disease.
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PMID:Rethinking the triggering inflammatory processes of chronic periaortitis. 1710 6

Intestinal adhesions are bands of fibrous tissue that connect the loops of the intestine to each other, to other abdominal organs or to the abdominal wall. Fibrous tissue formation is regulated by the balance between plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (tPA), which reciprocally regulate fibrin deposition. Several components of the inflammatory system, including cytokines, chemokines, cell adhesion molecules and neuropeptide substance P, have been reported to participate in adhesion formation. We have used cecal cauterization to develop a unique experimental mouse model of intestinal adhesion. Mice developed severe intestinal adhesion after this treatment. Adhesion development depended upon the interferon-gamma (IFN-gamma) and signal transducer and activator of transcription-1 (STAT1) system. Natural killer T (NKT) cell-deficient mice developed adhesion poorly, whereas they developed severe adhesion after reconstitution with NKT cells from wild-type mice, suggesting that NKT cell IFN-gamma production is indispensable for adhesion formation. This response does not depend on STAT4, STAT6, interleukin-12 (IL-12), IL-18, tumor necrosis factor-alpha, Toll-like receptor 4 or myeloid differentiation factor-88-mediated signals. Wild-type mice increased the ratio of PAI-1 to tPA after cecal cauterization, whereas Ifng(-/-) or Stat1(-/-) mice did not, suggesting that IFN-gamma has a crucial role in the differential regulation of PAI-1 and tPA. Additionally, hepatocyte growth factor, a potent mitogenic factor for hepatocytes, strongly inhibited intestinal adhesion by diminishing IFN-gamma production, providing a potential new way to prevent postoperative adhesions.
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PMID:Interferon-gamma is a therapeutic target molecule for prevention of postoperative adhesion formation. 1834 12

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

Little is known about innate immunity of neonates, particularly for very-preterm ones, which are more susceptible to immunologic damage due to their immature immune response. This cross-sectional, descriptive study in umbilical cord blood mononuclear cells describes the differences in innate immune response between 64 healthy neonates of different gestational ages (very-preterm, preterm, full-term). CD14(+) monocytes cultured with lipopolysaccharide (LPS) or LPS + interferon-gamma showed significant lower human leukocyte antigen-DR percentages for the very-preterm group in both unstimulated and LPS-stimulated cells. No differences were found for CD40(+)-cell percentages. We observed an increase in CD80 and a decrease in CD86 within all groups when stimulated with LPS or LPS + interferon-gamma. Interleukin-12 production was lower in very-preterm neonates. Adhesion capability of neonatal monocytes was similar and independent of gestational age. In summary, very-preterm-neonatal monocytes do not completely respond to LPS and, therefore, have diminished functions compared with preterm or full-term neonates.
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PMID:Impairment of stimulation ability of very-preterm neonatal monocytes in response to lipopolysaccharide. 1996 91


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