Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human endothelial leukocyte-adhesion molecule 1 (ELAM-1), a cell-surface glycoprotein expressed solely on cytokine-activated endothelial cells, mediates the adhesion of blood neutrophils, memory T-cells and some monocytes. ELAM-1, also known as E-selectin or leukocyte endothelial-cell-adhesion molecule 2, is a member of the lectin/epidermal-growth-factor/complement-regulatory-protein-like cell-adhesion molecule family, which includes structurally related molecules referred to as selectins. They are all involved in cell/cell adhesion, playing roles in leukocyte trafficking which are currently only partially defined. We report here the isolation and characterization of the murine equivalent of human ELAM-1. Murine ELAM-1 is encoded by a single-copy gene, spanning about 13 kb, which is structurally organized into 14 exons and 13 introns; very similar to that of its human counterpart. The exon/intron architecture exactly parallels the domain structure of the encoded protein. A murine ELAM-1-specific cDNA was cloned from heart tissue of an interleukin-1-(IL-1)-treated mouse. Its nucleotide sequence shows an overall similarity of 70% to human ELAM-1 cDNA. Transiently expressed in Cos cells, the encoded protein promotes the adhesion between recombinant cells and both human polymorphic nuclear cells, as well as HL60 cells expressing S-Lewis-x sugar moiety. Northern blot studies revealed by far the highest expression of the murine ELAM-1 gene in heart tissue and only low expression in lung tissue of IL-1-treated mice. Within the promoter, most of the recently identified regulatory elements are conserved. An exception is the nuclear factor (NF) kappa B box sequence, which, in the murine ELAM-1 promoter, does not correspond to the consensus NF kappa B sequence (Lenardo and Baltimore, 1989). Band-shift analyses show no binding to NF kappa B-like proteins. However, fusion of the murine ELAM-1 promoter to a chloramphenicol acetyltransferase reporter confers cytokine-inducible transcription, although at a lower level, when compared to the human ELAM-1 promoter. Our results demonstrate the existence of a murine homologue of the human gene and demonstrate for adhesion functional equivalence between the homologous proteins from the two species. In addition, we provide the first evidence of the utility of the murine model in addressing biological questions about the role which ELAM-1 plays in inflammation.
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PMID:Murine endothelial leukocyte-adhesion molecule 1 is a close structural and functional homologue of the human protein. 137 14

ELAM1 (endothelial leukocyte adhesion molecule 1, also known as E-selectin) is a highly tissue-specific adhesion molecule that is transiently and exclusively expressed on cytokine-induced endothelial cells. We have identified two proximal ELAM1 promoter elements and their DNA-binding factors that are, in addition to NF-kappa B, essential for ELAM1 transcription. Mutation of either element in promoter constructs carrying the first 383 nucleotides of the ELAM1 promoter markedly diminshed the expression of a fused chloramphenicol acetyltransferase reporter gene. Although multimers of either element failed to display enhancer activity on its own, fusion of the most upstream of these to the NF-kappa B element had a strong stimulatory effect. This site, ACATCAT, is recognized by a factor we have called NF-ELAM1. The site corresponds to NF-ELAM1's preferential binding sequence (A/T)CA(G/T)CA(G/T) as determined in a target definition assay. This element is identical to the T-cell delta A enhancer found in the T-cell receptor-alpha, -beta, and CD3 delta genes. Our results suggest that the delta A/NF-ELAM1 element can function as a modulator of NF-kappa B in endothelial cells both as well as a T-cell enhancer.
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PMID:A T-cell enhancer cooperates with NF-kappa B to yield cytokine induction of E-selectin gene transcription in endothelial cells. 138 98

The A20 gene product is a novel zinc finger protein originally described as a tumor necrosis factor alpha (TNF)-inducible early response gene in human umbilical vein endothelial cells (HUVEC). Its described function is to block TNF-induced apoptosis in fibroblasts and B lymphocytes, but more recently it has also been shown to play a role in lymphoid cell maturation. The mechanism of action of A20 is unknown. The aim of our study was to assess the effect of A20 upon endothelial cell activation. By transfecting bovine aortic endothelial cells (BAEC) with A20 as well as reporter constructs consisting of the promoters of genes known to be up-regulated during endothelial cell activation, i.e. E-selectin, interleukin (IL)-8, tissue factor (TF), and inhibitor of nuclear factor kappaBalpha (IkappaBalpha), we demonstrate that A20 expression inhibits gene up-regulation associated with TNF, lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), and hydrogen peroxide (H2O2)-induced endothelial cell (EC) activation. The mechanism of action of A20 is in part, or totally, due to the blockade of nuclear factor kappaB (NF-kappaB), as shown by its ability to suppress the activity of a NF-kappaB reporter. This effect is specific, as A20 does not block a noninducible, constitutively expressed reporter, Rous sarcoma virus-luciferase (RSV-LUC); nor does it block the c-Tat-inducible, NF-kappaB-independent reporter, human immunodeficiency virus-chloramphenicol acetyltransferase (HIV-CAT). How A20 blocks NF-kappaB is unclear, although we demonstrate that it does not affect p65 (RelA)-mediated gene transactivation. The inhibition of endothelial cell activation by A20 is a novel function for A20.
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PMID:A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. 866 99

The predominant early histological changes in irradiated tissues are edema and leukocyte infiltration. Cell adhesion molecules (CAMs) are required for the extravasation of leukocytes from the circulation. To study the role of CAMs in the pathogenesis of radiation-mediated inflammation, we quantified the expression of P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 glycoproteins on the surface of irradiated human endothelial cells. We found that E-selectin and ICAM-1 expression increased after irradiation, whereas there was no increased expression of other cytokine-inducible adhesion molecules (P-selectin or vascular cell adhesion molecule-1). We found a dose- and time-dependent increase in radiation-induced expression of both E-selectin and ICAM-1. Furthermore, the threshold dose for E-selectin expression was 1 Gy, whereas the threshold dose for ICAM-1 synthesis was 5 Gy of X-rays. Northern blot analysis of RNA from irradiated endothelial cells demonstrated that ICAM-1 is expressed at 3-6 h following irradiation. No de novo protein synthesis was required for increased ICAM-1 mRNA expression. The 1.1-kb segment of the 5' untranslated region of the ICAM-1 gene was sufficient for X-ray induction of chloramphenicol acetyltransferase reporter gene expression. We measured whether ICAM-1 mediates adhesion of leukocyte to the irradiated endothelium and found that leukocyte adhesion occurred concurrently with ICAM-1 induction. Radiation-mediated leukocyte adhesion was prevented by anti-ICAM-1 blocking antibodies. These data indicate that ICAM-1 participates in the inflammatory response to ionizing radiation. Moreover, radiation induction of these CAMs occurs in the absence of tumor necrosis factor and interleukin 1 production.
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PMID:Cell adhesion molecules mediate radiation-induced leukocyte adhesion to the vascular endothelium. 891 50