Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular cell adhesion molecule-1 (VCAM-1), a mononuclear leukocyte adhesion molecule, is expressed in cultured vascular endothelial cells activated by cytokines and is induced in rabbit aortic endothelium in vivo within 1 week after initiation of an atherogenic diet. We now demonstrate that vascular smooth muscle cells can also express VCAM-1 in rabbit atherosclerotic lesions in vivo and in response to cytokines in vitro. Immunohistochemical staining of aortas from rabbits fed a 0.3% cholesterol-containing diet revealed that a portion of smooth muscle cells within intimal foam cell-rich lesions expressed VCAM-1. The intimal VCAM-1-expressing cells localized predominantly in regions above the internal elastic lamina. These VCAM-1-positive cells had the typical spindle shape of smooth muscle cells but had reduced alpha-actin expression in comparison to normal medial smooth muscle cells, and did not bear markers for endothelium, macrophages, and T cells. In culture, rabbit aortic smooth muscle cells expressed VCAM-1 mRNA and protein in a time- and concentration-dependent fashion when exposed to interferon-gamma or Gram-negative bacterial lipopolysaccharide. Cultured human vascular smooth muscle cells also expressed VCAM-1 mRNA and protein in response to lipopolysaccharide, interferon-gamma, and interleukin-4. The monokines interleukin-1 alpha and tumor necrosis factor-alpha did not induce VCAM-1 expression in either rabbit or human vascular smooth muscle cells. Inducible VCAM-1 expression by vascular smooth muscle cells in vivo during hypercholesterolemia and in vitro in response to certain cytokines suggests a broader range of VCAM-1 functions in vascular biology than heretofore appreciated.
...
PMID:Inducible expression of vascular cell adhesion molecule-1 by vascular smooth muscle cells in vitro and within rabbit atheroma. 750 83

It is well accepted that the induction of endothelial cell (EC) adhesion molecules is a critical component in acute inflammatory responses as well as allogeneic interactions in vascularized allografts and, possibly, atherogenesis. The "inflammatory triad" of interleukin 1 (IL-1), tumor necrosis factor, and lipopolysaccharide are potent stimulators of the EC activation/adhesion molecules intercellular adhesion molecule 1 (ICAM-1), endothelial-leukocyte adhesion molecule 1 (ELAM-1), and vascular cell adhesion molecule 1 (VCAM-1). To address whether there exist differing thresholds to cytokine-mediated EC activation, we utilized a panel of genetically distinct human umbilical vein EC lines, assessing their modulated EC surface expression and transcriptional responses to cytokines, with regard to the cell adhesion molecules (CAMs) ELAM-1, ICAM-1, and VCAM-1. With submaximal concentrations of cytokine, EC ELAM-1 surface expression varied from negligible to marked. This phenotypic response was maintained over numerous passages in culture and was observed in ex vivo organ culture analyses with cytokine-treated umbilical vein sections. Relative patterns of ELAM-1, ICAM-1, and VCAM-1 induction were similar in response to multiple stimuli (IL-1, tumor necrosis factor, and lipopolysaccharide, but not phorbol 12-myristate 13-acetate). Nuclear run-off experiments demonstrated that the "high responder" phenotype is a consequence of enhanced transcriptional activation of the CAM genes in response to IL-1 (1 unit/ml), whereas transcriptional responses in "low responders" are minimal. Despite the known involvement of NF-kappa B in endothelial CAM transcription, gel shift assays failed to demonstrate a correlation between the levels of IL-1-mediated nuclear NF-kappa B expression and CAM induction in high and low responding lines. We postulate that varying EC activation thresholds to cytokines observed here, in vitro, may be a critical determinant in the susceptibility to vasculopathic states.
...
PMID:Heterogeneous activation thresholds to cytokines in genetically distinct endothelial cells: evidence for diverse transcriptional responses. 751 30

Extensive monocyte recruitment is an early phenomenon associated with the development of atherosclerotic lesions, suggesting an active role for the involvement of adhesion receptors expressed by endothelial cells. In this study we describe the contribution of hemodynamic shear forces in regulating the expression of a few of the monocyte adhesion receptors, including intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and E-selectin on endothelial cells. A parallel plate flow chamber and recirculating flow loop device was used to expose human umbilical vein endothelial cells (HUVECs) to different levels of shear (2-25 dyn/cm2). Subsequently the cells were analyzed either for shear induced changes in the mRNA levels of adhesion receptors by Northern blot analyses or for changes in the surface expression of ICAM-1 using flow cytometry. Results from the fluorescence analysis showed a transient increase in the surface expression of ICAM-1, 12 hr after exposure to 25 dyn/cm2 shear, returning to basal levels within 24 hr. This was quite different from the time dependent response of ICAM-1 to lipopolysaccharide (LPS), where ICAM-1 expression was maximally induced 18-24 hr post-stimulus. ICAM-1 mRNA level appeared slightly elevated after exposure to shear for 1 hr, compared to basal values, but dropped below basal levels within 6 hr. This biphasic response was seen irrespective of the magnitude of applied shear stress. VCAM-1 mRNA expression, in contrast, decreased below the baseline expression within an hour after onset of flow, and appeared to be considerably down-regulated within 6 hr. After exposure to shear for 24 hr, no increase in mRNA levels could be detected for either molecule, at any shear magnitude. E-selectin mRNA was less responsive to shear stress, especially at the lower magnitudes of shear. After an hour of exposure to flow E-selectin mRNA level appeared slightly reduced compared with control levels, but it remained at this level even after 6 hr of flow. These results indicate that the expression of adhesion receptors is sensitive to local shear stresses in a manner that is molecule specific in the short term even though prolonged exposure to flow results in similar down-regulation for both ICAM-1 and VCAM-1.
...
PMID:Shear stress-mediated changes in the expression of leukocyte adhesion receptors on human umbilical vein endothelial cells in vitro. 754 62

Vascular cell adhesion molecule-1 (VCAM-1) is an endothelial cell membrane glycoprotein that has been implicated in leukocyte/endothelial cell interactions in inflammation. In this study, we report the expression of VCAM-1 in primary cultures of human brain microvessel endothelial cells (HBMEC) under standard conditions and following bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), or interferon-gamma (IFN-gamma) treatment. Surface expression was detected and quantitated by light and immunogold electron microscopy and ELISA. Unstimulated cerebral endothelial cells (EC) constitutively expressed low levels of VCAM-1. LPS, TNF-alpha, or IL-1 beta increased the overall intensity of surface staining and the percentage of cells expressing VCAM-1 in a time- and concentration-dependent manner. LPS had the most potent effect, followed by TNF-alpha and then IL-1 beta. IFN-gamma did not upregulate VCAM-1. The level of VCAM-1 expression increased by 12-24 hr and returned to unstimulated levels by 48 hr. Immunoelectron microscopy demonstrated that VCAM-1 was preferentially localized on the apical as compared to the basal surface in both unstimulated and cytokine-treated cells. In addition, the intensity of immunostaining was significantly greater in stimulated versus unstimulated EC. The polarization and significant upregulation of VCAM-1 after cytokine treatment suggest a possible role of this adhesion molecule in inflammatory and autoimmune processes within the central nervous system.
...
PMID:Expression of vascular cell adhesion molecule-1 (VCAM-1) by human brain microvessel endothelial cells in primary culture. 754 72

Increasing evidence indicates that interaction of cells with fibronectin (Fn) affects many aspects of cellular responses including growth, morphology, differentiation, and activation. However, it is not known whether Fn could activate macrophages for the tumor cell killing. Here we report that Fn provides a signal for murine macrophage activation to tumoricidal activity. Tumoricidal activity was determined by the release of 51Cr from prelabeled P815 mastocytoma target cells. Fn alone had no effect, whereas recombinant interferon-gamma (rIFN-gamma) weakly induced C57BL/6 murine macrophages to kill P815 mastocytoma cells. However, combination of Fn with rIFN-gamma synergized to activate macrophages to lyse tumor cells in a dose dependent manner. Secretion of nitric oxide (NO) correlated with tumor cell killing, and the activated macrophages failed to kill tumor cell targets in the presence of NG-monomethyl-L-arginine (NGMMA), a competitive inhibitor of NO synthase (NOS). Fn, unlike lipopolysaccharide (LPS), alone had no effect on NO synthesis by itself and did not induce bioactive tumor necrosis factor-alpha (TNF-alpha) secretion from murine peritoneal macrophages. The data illustrate the potential for Fn to activate macrophage-mediated antitumor mechanisms in addition to its better characterized role as a cell adhesion molecule.
...
PMID:Fibronectin activates murine peritoneal macrophages for tumor cell destruction in the presence of IFN-gamma. 783 12

The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
...
PMID:Intercellular adhesion molecule-1. 883 67

Recent studies suggest that increased vascular cell adhesion molecule-1 (VCAM-1) expression on vascular endothelium in bronchial mucosa biopsies correlates with interleukin-4 (IL-4) levels in bronchiolar lavage fluid of allergic asthmatics. The severity of asthma in patients allergic to house dust mite has also been shown to correlate with lipopolysaccharide (LPS), rather than allergen, concentration in dust. We hypothesized that to induce effective VCAM-1 expression in human lung microvascular endothelial cells (HLMVEC), IL-4 may require the presence of a co-stimulus such as LPS. To test this hypothesis we measured, by enzyme-linked immunosorbent assay, induction of cell adhesion molecule expression on, and human eosinophil adhesion to, cultured HLMVEC monolayers pretreated with IL-4 alone or combined with LPS. IL-4 synergized with LPS to induce VCAM-1 expression at 24, 48, or 72 h, whereas IL-4 alone induced expression at 72 h only. IL-4 did not induce expression of intercellular adhesion molecule-1 or E-selectin or alter LPS-induced expression of either. Pre-exposure of HLMVEC to LPS or IL-4 (1 h), followed by IL-4 or LPS, respectively (23 h), also induced VCAM-1 expression. Eosinophil adhesion to HLMVEC monolayers treated with IL-4 and LPS together, but not alone, significantly (P < 0.001) increased from 9.6 +/- 1.5% (control) to 26.9 +/- 3.3% and was inhibited by a monoclonal antibody against the VCAM-1 ligand, very late antigen-4. Analysis of VCAM-1 mRNA revealed synergism between IL-4 and LPS which may, in part, contribute to enhanced VCAM-1 expression. These results suggest that the presence of a co-stimulus such as LPS may be necessary for IL-4 to effectively induce VCAM-1 expression in lung microvasculature.
...
PMID:Interleukin-4 and lipopolysaccharide synergize to induce vascular cell adhesion molecule-1 expression in human lung microvascular endothelial cells. 956 32

During inflammation, activated monocytes (Mo) migrate into tissues where they interact with extracellular matrix components such as hyaluronate (HA), produced in high amounts at inflammatory sites. We determined whether Mo that had invaded sites of cutaneous inflammation bind HA and express the putative HA receptors CD44 isoforms, ICAM-1, or receptor for hyaluronate-mediated motility (RHAMM). In cutaneous inflammation, activated infiltrating Mo displayed high HA avidity and expressed epitopes encoded by CD44s, CD44 variant exons v3, v4, v5, v6, v7, and v9, and ICAM-1, but not RHAMM. We further investigated how activation affects the avidity of Mo for HA and which receptors were responsible for such binding. Mo freshly purified from human peripheral blood bound little HA and expressed CD44s but no epitopes encoded by CD44v exons, ICAM-1, or RHAMM. During short-term tissue culture, Mo upregulated their HA avidity and expression of ICAM-1, CD44s, and epitopes encoded by CD44v, all of which were further augmented by IFN-gamma or lipopolysaccharide, whereas RHAMM was not detectable. Thus in vitro activated Mo resembled Mo that had migrated to inflammatory sites in vivo. Lipolysaccharide or IFN-gamma-induced HA binding was inhibited by more than 90% with monoclonal antibodies directed against N-terminal HA binding domains of CD44s, but not by monoclonal antibodies against CD44v epitopes or ICAM-1. In conclusion, we show that upon in vitro or in vivo activation, Mo enhance their capacity to bind HA. This is critically dependent upon the expression ofCD44s epitopes. Regulated CD44-HA interactions may be important for the ability of Mo to migrate into and within sites of inflammation and for Mo effector functions.
...
PMID:Activation-dependent modulation of hyaluronate-receptor expression and of hyaluronate-avidity by human monocytes. 969 22

We examined the tissue distribution of adhesion molecule gene expression in mice treated intravenously with interleukin (IL)-1 beta. E-selectin mRNA expression was selectively induced in the heart by IL-1 beta, but only slight or no induction was observed in other organs. On the other hand, intercellular adhesion molecule-1 mRNA expression was inducible in all organs examined, although it showed the strongest induction in the lung and the weakest responses in the brain and skin. Vascular cell adhesion molecule-1 mRNA was also inducible in all organs with the exception of the skin, but it was induced most markedly in the lung and the heart. The accessibility of IL-1 beta to the heart was less than that to other organs except the brain. Similar tissue-specific induction of these mRNAs was also seen when tumor necrosis factor (TNF)-alpha or lipopolysaccharide was substituted for IL-1 beta. Analysis of E-selectin mRNA expression in the heart by in situ hybridization indicated that expression was most prominent in microvascular endothelial cells and some other stromal cells, but this transcript was not seen in the lung. Although intercellular adhesion molecule-1 mRNA expression was restricted to the endothelium lining the capillaries and small arteries in the heart, its distribution in the lung covered not only the endothelium but also the cells composing the alveolar septa. In contrast, vascular cell adhesion molecule-1 mRNA expression was most prominent in endothelial cells of larger vessels in both the heart and the lung. Our results demonstrate that expression of adhesion molecules is tissue- and cell type-specific and that endothelial cells differentially express adhesion molecules depending on the size of the blood vessels.
...
PMID:Interleukin-1beta induces tissue- and cell type-specific expression of adhesion molecules in vivo. 971 37

Increased nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) has been associated with intestinal inflammation, including human inflammatory bowel disease. However, NO can downregulate endothelial activation and leukocyte adhesion, critical steps in the inflammatory response. Using primary cultures of human intestinal microvascular endothelial cells (HIMEC), we determined the role of NO in the regulation of HIMEC activation and interaction with leukocytes. Both nonselective (NG-monomethyl-L-arginine) and specific (N-iminoethyl-L-lysine) competitive inhibitors of iNOS significantly increased binding of leukocytes by HIMEC activated with cytokines and lipopolysaccharide. Increased adhesion was reversible with the NOS substrate L-arginine and was not observed in human umbilical vein endothelial cells (HUVEC). Activation of HIMEC significantly upregulated HIMEC iNOS expression and NO production. NOS inhibitors did not augment cell adhesion molecule levels in activated HIMEC but did result in sustained increases in intracellular reactive oxygen species. In addition, antioxidant compounds reversed the effect of NOS inhibitors on HIMEC-leukocyte interaction. Taken together, these data suggest that after HIMEC activation, iNOS-derived NO is an endogenous antioxidant, downregulating leukocyte binding and potentially downregulating intestinal inflammation.
...
PMID:iNOS expression in human intestinal microvascular endothelial cells inhibits leukocyte adhesion. 972 73


1 2 3 4 5 6 7 8 9 Next >>

---