Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An azaindolidine derivative, SJC13, selectively inhibits expression and mRNA synthesis of E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS). The present experiments were performed to determine the in vivo effects of SJC13 against the lethality of LPS. In a mouse model of septic shock, intravenous administration of SJC13 5 min prior to LPS injection prevented significantly the lethality at doses of 3 mg/kg and 10 mg/kg. The prophylactic effect was dose-dependent. When injected up to 1 h after LPS injection, SJC13 inhibited significantly the lethality. Neutrophil emigration into lung tissues during sepsis induced with LPS, as assessed by lung myeloperoxidase (MPO) content and histological examination, was significantly prevented by SJC13 administration. These data demonstrate that SJC13 has therapeutic anti-inflammation potential in vivo.
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PMID:Protection against septic shock in mice with SJC13, an azaindolidine derivative that is a cell adhesion molecule inhibitor. 889 55

A monoclonal antibody (mAb), designated mNI-58A, was produced by immunizing mice with the lipopolysaccharide (LPS)-stimulated monocyte-like cell line, U937. The antigen defined by mNI-58A was widely expressed on various lymphoid cells and all cell lines examined except the erythroid cell line, K562. When the reactive patterns between mNI-58A and the mAbs to various human differentiation antigens (CD11a, CD11b, CD11c, CD14, CD16, CD18, CD23, CD28, CD29, CD31, CD43, CD44, CD45RA, CD50, CD54, CD58, CD80, CD102, CD106, HLA-class I and-class II antigen) were compared, that of mNI-58A was found to be similar to those of the leukocyte function-associated antigen-1 (LFA-1) mAbs. Using a competitive immunofluorescence binding assay it was found that the preincubation with one of the CD11a mAbs, 2F12 completely blocked the subsequent binding of mNI-58A. mNI-58A prevented the homotypic cell aggregation of the phorbol myristate acetate (PMA)-activated U937 cells (referred to as PMA-U937) and PMA-activated Epstein-Barr virus (EBV)-transformed B cell lines, B-85 and Mann. mNI-58A markedly induced the spread formation of the PMA-U937 cells following this blocking of the homotypic cell aggregation, whereas 2F12 did not under the same condition. The spread formation induced by mNI-58A was completely blocked by cytochalasin B (CyB), cytochalasin D (CyD), cycloheximide (CHX) or protein kinase C inhibitors, sphingosine and H-7. The U937 cells markedly adhered to the tumor necrosis factor-alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells (HUVECs) and also to the extracellular matrix protein, fibronectin, but mNI-58A did not enhance or block these adhesion process. mNI-58A precipitated two glycoproteins with molecular weight 180 kDa and 95 kDa as determined by SDS-PAGE analysis, which were identical to the LFA-alpha (CD11a) and beta (CD18) chains of leukocyte integrin precipitated by the CD11a mAbs, respectively. Sequential immunoprecipitation studies using the CD11a mAb (2F12) also indicate that mNI-58A recognizes an epitope on the alpha-chain of the LFA-1 molecule. The ability of mNI-58A to block the PMA-U937 cells and to induce the spread formation of these cells suggests that mNI-58A is a novel mAb reacting with an epitope on the alpha-chain of LFA-1 different from those recognized with the existing CD11a mAbs.
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PMID:A novel monoclonal antibody mNI-58A against the alpha-chain of leukocyte function-associated antigen-1 (LFA-1) blocks the homotypic cell aggregation and actively regulates morphological changes in the phorbol myristate acetate (PMA)-activated human monocyte-like cell line, U937. 889 74

The functions of different populations of peripheral blood monocytes in the course of an inflammatory reaction are presently not fully understood. In particular, the mechanisms for their specific recruitment to an inflammatory site are not yet known. We investigated a dexamethasone (Dex)-inducible monocyte subtype and its adhesion to either unstimulated or lipopolysaccharide (LPS)- or interferon (IFN)-gamma-stimulated human umbilical vein endothelial cells (HUVEC). The Dex-induced monocytes were characterized by the expression of the surface glycoprotein RM3/1. It was found that pretreatment of monocytes with Dex increased their adhesion to unstimulated and stimulated HUVEC. This increase in adhesion was paralleled by the expression of the RM3/1 surface molecule. Treatment with cyclosporin A (CsA) caused a down-regulation of the RM3/1 density per cell by 67% and also decreased adhesion to HUVEC. In contrast, the expression of other adhesion molecules remained unaffected by Dex or CsA treatment. Treatment of Dex-induced monocytes with antibodies against RM3/1, CD11a, CD11b, CD11c, CD14 and CD18 resulted in suppression of adhesion to stimulated HUVEC by 46%, 18%, 17%, 12%, 25% and 15%, respectively. Antibodies to the known adhesion molecules on endothelial cells (vascular cell adhesion molecule-1, E-selectin) did not block adhesion of Dex-induced monocytes. However, the combination of antibodies to RM3/1 and CD14 inhibited adhesion to LPS-stimulated HUVEC by 74%. These effects were also seen on IFN-gamma-stimulated HUVEC, where adhesion of Dex-induced monocytes was blocked with antibodies to RM3/1 + CD14 by 63%. From this, it is concluded that the RM3/1-molecule is a novel surface molecule that contributes to the adhesion of cortisone-induced monocytes to LPS or cytokine-stimulated endothelial cells.
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PMID:Identification of a novel surface molecule, RM3/1, that contributes to the adhesion of glucocorticoid-induced human monocytes to endothelial cells. 892 66

Human bone marrow endothelial cells (HBMEC) are intimately involved in the homing of hematopoietic progenitor cells (HPC) to the bone marrow and in the regulation of proliferation and differentiation of these cells. Because availability of primary HBMEC and their capacity to be cultured in vitro are limited, we used isolated HBMEC to establish a cloned cell line by microinjection of a recombinant plasmid expressing simian virus 40 early genes under the control of a deletion mutant of the human vimentin promoter. Serum requirements for growth of a transformed HBMEC line (TrHBMEC) were markedly decreased compared with those of primary cells, and added growth factors were not required for proliferation. Cells took up acetylated low-density lipoprotein normally, bound to Ulex europaeus lectin, and stained positively for von Willebrand factor, P-selectin, CD31, CD34, CD44, very late antigen-5, and intercellular adhesion molecule-2 (ICAM-2). After treatment with TNF-alpha or lipopolysaccharide, TrHBMEC increased surface expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and ICAM-1 in a manner similar to primary HBMEC. In contrast, IL-1 beta elicited much less up-regulation of these adhesion molecules than in primary cells. In previous work, we reported that, in a flow adhesion model, rolling of peripheral blood CD34+ cells on primary HBMEC was E-selectin-dependent, whereas VCAM-1 and ICAM-1 contributed to firm adhesion. In the present study, we show that HPC adhere in a similar way to TrHBMEC. A less-pronounced role for VCAM-1 and ICAM-1 was found in the adhesion of HPC to human umbilical vein endothelial cells. Furthermore, significantly more CD34+ cells adhered to TNF-alpha-stimulated HBMEC and TrHBMEC than to similarly stimulated human umbilical vein endothelial cells. These data emphasize the importance of using microvessel HBMEC for studying the homing of HPC to the bone marrow, and indicate the usefulness of the above-described bone marrow endothelial cell line.
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PMID:Characterization of a newly established human bone marrow endothelial cell line: distinct adhesive properties for hematopoietic progenitors compared with human umbilical vein endothelial cells. 901 Apr 47

Leukocyte adherence to the endothelium is an essential component of the inflammatory response during rickettsial infection. In vitro, Rickettsia conorii infection of endothelial cells enhances the expression of adhesive molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in a time- and dose-dependent manner. Rickettsial lipopolysaccharide does not seem to be involved, because polymyxin B does not reduce their expression. The intracellular presence of the organism and de novo host protein synthesis are required for expression of cell adhesive molecules, since rickettsial inactivation by formol and pretreatment of cells with cycloheximide inhibits an increase in expression. The contribution of interleukin-1alpha (IL-1alpha) to this endothelial adhesive phenotype was shown by inhibitory experiments 8 and 24 h after infection with IL-1 receptor antagonist and IL-1alpha blocking antibodies. Enhanced adherence of mononuclear cells to infected endothelial cells involved VCAM-1- and ICAM-1-dependent mechanisms at the late phase of the inflammatory response. This endothelial adhesive phenotype may constitute a key pathophysiologic mechanism in R. conorii-induced vascular injury.
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PMID:Rickettsia conorii infection enhances vascular cell adhesion molecule-1- and intercellular adhesion molecule-1-dependent mononuclear cell adherence to endothelial cells. 912 78

We evaluated the expression of mRNAs for intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1) in cultured neonatal rat cardiac myocytes and in the rat heart by the reverse transcription-polymerase chain reaction with gene specific primers. Bacterial lipopolysaccharide (LPS) and interferon-gamma induced gene expression for ICAM-1, VCAM-1, and ELAM-1 in cultured cardiac myocytes. While mRNA for any of these adhesion molecules was very low or negligible in hearts of control rats, the three mRNAs were substantially induced in hearts 3h after the injection of LPS. Results show that mRNAs for the three inducible adhesion molecules are expressed in cultured cardiac myocytes and rat heart tissues and are enhanced by immune stimulation, suggesting their involvement in cardiac inflammatory disorders.
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PMID:Induction of mRNAs for ICAM-1, VCAM-1, and ELAM-1 in cultured rat cardiac myocytes and myocardium in vivo. 913 29

T-cells and monocytes are the first cells infiltrating the arterial intima during the early stages of atherogenesis. Recently our laboratory has provided evidence that T-cells isolated from atherosclerotic intima reacts against heat shock protein 60 (Hsp60). Transmigration of activated T-cells into the intima is mediated by adhesion molecules (ICAM-1; VCAM-1; ELAM-1) expressed on activated endothelial cells. Here we studied the potential of cytokines (TNF-alpha, IFN-gamma, IL-1). Escherichia coli lipopolysaccharide (LPS), native and oxidized low-density lipoprotein (LDL; oxLDL) and high temperature to induce adhesion molecules as well as Hsp60 and Hsp70 expression in human endothelial cells (EC). On Northern blots, a strong signal for ICAM-1, VCAM-1 and ELAM-1 was detected after 4 h, which thereafter declined, but did not reach the basal level of untreated control cells. Heat shock induced the expression of Hsp60 and Hsp70 but not of adhesion molecules. EC were cultivated in serum-free medium, which led to the expression of adhesion molecule transcripts. Addition of LDL or oxLDL to these ECs did not alter the expression of these transcripts. The production of adhesion molecule proteins was analysed by flow cytometry. In human venous endothelial cells (HVEC) and human arterial endothelial cells (HAEC) ICAM-1 and VCAM-1 production was permanently highly induced, whereas the high level of ELAM-1 production at 4 h disappeared after 24 h. Furthermore, only HAEC, but not HVEC, produced ICAM-1, VCAM-1 and ELAM-1 after stress by moderately and highly oxLDL. LDL and oxLDL did not induce the production of Hsp60 and Hsp70. The present study demonstrates the co-expression of Hsp60 and adhesion molecules in arterial and venous EC in response to cytokine and LPS exposure, and that oxLDL is an efficient inducer of adhesion molecules in arterial EC and not in venous EC. These features provide the prerequisites for a cellular immune reaction against Hsp60 expressed by stressed EC in the initial stages of atherosclerosis.
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PMID:Co-expression of ICAM-1, VCAM-1, ELAM-1 and Hsp60 in human arterial and venous endothelial cells in response to cytokines and oxidized low-density lipoproteins. 925 Apr

An increased adherence of leukocytes to the vascular endothelium appears to be a crucial event in the development of atherosclerosis. The role of endothelial cell adhesion molecules is gaining increasingly interest in this context. Several studies show an influence of lipoproteins, especially low-density-lipoproteins on adhesion molecule stimulation. The aim of our study was to analyze the atherogenic potential of postprandially elevated serum triglyceride levels by investigating the impact of postprandial lipoproteins (chylomicrons (CH, isolated 4 h after a standard oral lipid load)) on the expression of E-selectin (endothelial leukocyte adhesion molecule-1, ELAM-1) and VCAM-1 (vascular cell adhesion molecule-1). In addition we used chylomicrons that had been incubated with lipoprotein lipase (50 U/ml) for 3 h (CH-LPL). The endotoxin lipopolysaccharide (LPS) served as positive control for adhesion molecule stimulation. Human umbilical vein endothelial cells (HUVEC) were incubated with the samples for 4 h and expression of E-Selectin and VCAM-1 was determined by ELISA. The expression of E-selectin was induced by LPS (530 +/- 64% compared to the basal activity (= 100%)) and by CH (342 +/- 94%); CH-LPL had no effect on E-Selectin expression. VCAM-1 expression was stimulated by LPS (395 +/- 221%) and similarly by CH-LPL (322 +/- 136%) but considerably stronger by CH (1245 +/- 324). In summary, chylomicrons induced an enhancement of the expression of both adhesion molecules, which closely resembled or even exceeded the endotoxin-induced stimulation. Interestingly, this effect was diminished or even reversed after incubation with LPL.
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PMID:Chylomicrons induce E-selectin and VCAM-1 expression in endothelial cells. 928 41

Inducible vascular cell adhesion molecule-1 (VCAM-1) in glomerular mesangial cells (GMC) exposed to lipopolysaccharide (LPS) in vitro involves the activation of nuclear factor-kappa B (NF-kappa B) and its interaction with the proximal VCAM-1 promoter. We used a murine model to assess the effect of the antioxidant, N-acetyl cysteine on GMC activation in vivo. Single intraperitoneal administration of N-acetyl cysteine completely suppressed LPS-induced VCAM-1 expression on the GMC surface. When an oligonucleotide spanning the NF-kappa B binding region of the VCAM-1 promoter was incubated with extracts from the renal cortex of LPS-treated animals, a single nucleoprotein complex formed. This complex was composed of p50 and p65, but not p52, c-Rel, or RelB, and its formation was dramatically inhibited by pretreatment with N-acetyl cysteine, D,L-Buthionine-[S,R]-sulfoximide, a compound that depletes glutathione, augmented VCAM-1 expression inducible with a suboptimal amount of LPS to levels comparable with using 50 micrograms of LPS alone, D,L-Buthionine-[S,R]-sulfoximide also potentiated the p50-p65 binding activity induced with a suboptimal amount of LPS. These data provide a redox-sensitive, transcriptional link between NF-kappa B and VCAM-1 in GMC in vivo and implicate oxidative stress as an important regulatory signal in the pathogenesis of glomerular mesangial cell disorders.
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PMID:N-acetyl cysteine blocks mesangial VCAM-1 and NF-kappa B expression in vivo. 935 47

The induction of vascular cell adhesion molecule-1 (VCAM-1) expression by tumor necrosis factor (TNF)-alpha requires the activation of nuclear factor-kappaB (NF-kappaB) via a process involving the phosphorylation and degradation of its cytoplasmic inhibitor, IkappaBalpha. We have shown that nitric oxide (NO) decreases VCAM-1 expression via inhibition of NF-kappaB activation. To determine how NO inhibits NF-kappaB, we studied the fate of IkappaBalpha following TNF-alpha stimulation in the presence of NO donors S-nitrosoglutathione and sodium nitroprusside. Activation of NF-kappaB by TNF-alpha occurred within 15 min and coincided with rapid degradation of IkappaBalpha. Co-treatment with NO donors did not prevent IkappaBalpha phosphorylation or degradation. However, after 2 h of TNF-alpha stimulation, NO donors inhibited NF-kappaB activation and augmented IkappaBalpha resynthesis and nuclear translocation by 2.5- and 3-fold, respectively. This correlated with a 75% reduction in TNF-alpha-induced VCAM-1 expression. In a time-dependent manner, NO donors alone caused the nuclear translocation of IkappaBalpha. To confirm that NO donors have similar effects as endogenously derived NO, murine macrophage-like cells, RAW264.7, were co-cultured with endothelial cells. Induction of RAW264.7-derived NO inhibited lipopolysaccharide-induced endothelial VCAM-1 expression, which was reversed by the NO synthase inhibitor Nomega-monomethyl-L-arginine. These findings indicate that NO inhibits NF-kappaB activation and VCAM-1 expression by increasing the expression and nuclear translocation of IkappaBalpha.
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PMID:Inhibition of endothelial vascular cell adhesion molecule-1 expression by nitric oxide involves the induction and nuclear translocation of IkappaBalpha. 938 44


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