UNIPROT:P43026 - FACTA Search

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

Incubation of primary cultures of rat hepatocytes with lipopolysaccharide (LPS), S-[2,3-bis(palmitoyloxy)-(2-R, S)-propyl]-N-palmitoyl-(R)-Cys-Ser-Lys4 (TPP), a synthetic lipopeptide present in bacterial cell wall lipoproteins, or with phorbol 12,13-dibutyrate (PDBu) induced an increase in nitric oxide synthesis through the expression of type II nitric oxide synthase (iNOS). Transfection of hepatocytes with a HindII fragment corresponding to the promoter region of the murine iNOS gene (from nucleotide -1588 to +165) resulted in the expression of the reporter gene when cells were stimulated with these factors. The transcription factors activated by these stimuli involved an increase in the nuclear content of proteins that bind to kappaB, AP-1, GAS, and SIE sequences. Inhibition of NF-kappaB activation with pyrrolidine dithiocarbamate eliminated the expression of iNOS in hepatocytes stimulated with LPS, TPP, or PDBu. In addition to this, transfection of hepatocytes with promoter mutants in which a sequential 2-base pair change within the kappaB sites was introduced (position -971 to -961 and -85 to -75, respectively), resulted in approximately 17 and 35%, respectively, of the activity of the naive promoter. Simultaneous mutation of both kappaB sites abolished the promoter activity. Analysis of the proteins involved in kappaB binding showed the presence of p50/p65 dimers in the nuclei of activated cells at the time that an important decrease of IkappaB-alpha was observed soon after cell stimulation with LPS, TPP, or PDBu. However, only LPS was able to decrease the amount of IkappaB-beta. These results suggest that LPS, TPP, and PDBu, although activating different signal transduction pathways, use a common mechanism mediating iNOS expression in cultured hepatocytes.
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PMID:Evidence for common mechanisms in the transcriptional control of type II nitric oxide synthase in isolated hepatocytes. Requirement of NF-kappaB activation after stimulation with bacterial cell wall products and phorbol esters. 893 60

Immunoglobulin heavy chain (IgH) class switch recombination and regulation of IgH expression levels are processes suggested to be controlled by the IgH 3' enhancer. Here we demonstrate that CD40 or IgM receptor stimulation of primary B cells results in transactivation of this enhancer. 4-Hydroxy-3-nitrophenylacetyl (NIP)-BSA induction of a K46 B cell line expressing a chimeric NIP-specific CD40 single chain receptor results in a ligand receptor-dependent response of a 3' enhancer ETS/AP-1 minimal promoter construct. Gel retardation analysis and genomic footprinting experiments reveal that CD40 or IgM induction recruits NFAB (nuclear factors of activated B cells) to the ETS/AP-1 motif. While IgM signalling recruits c-Fos, JunB and Elf-1 (NFAB-I), only JunB and Elf-1 were observed following CD40 signalling (NFAB-II). CD40 signalling, however, induces a Fos family-related partner for JunB, which may account for the transcriptional activity observed by NFAB-II in K46 cells. We propose a model whereby CD40 and IgM receptor-mediated signalling converge in the process of 3' enhancer activation in B lymphocytes. Our data provide a putative molecular explanation as to why CD40L-deficient mice, and possibly patients with hyper-IgM syndrome, are unable to undergo T cell-dependent class switch recombination but respond properly upon lipopolysaccharide-induced switch recombination.
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PMID:A T cell controlled molecular pathway regulating the IgH locus: CD40-mediated activation of the IgH 3' enhancer. 897 95

Tissue factor (TF) expression by peripheral blood monocytes during sepsis initiates intravascular thrombosis. Bacterial lipopolysaccharide (LPS) rapidly induces TF gene transcription in monocytes. The human TF promoter contains binding sites for the transcription factors AP-1, c-Rel/p65, Egr-1, and Sp1. NF-kappa B/Rel proteins have been shown to physically interact with both AP-1 and Sp1 proteins. In this study, we investigated the role of these transcription factors in uninduced and LPS-induced TF gene expression in human monocytic THP-1 cells. Deletional analysis indicated that five Sp1 sites mediated basal expression in uninduced cells. The two AP-1 sites bound c-Fos/c-Jun heterodimers in both unstimulated and LPS-stimulated cells. Maximal LPS induction of the TF promoter required the two AP-1 sites and the kappa B site within the LPS response element. Disruption of the conserved spacing between the proximal AP-1 site and the kappa B site abolished LPS induction. Replacement of the two AP-1 sites with intrinsically bent DNA partially restored LPS induction, suggesting an additional structural role for the AP-1 sites. Synergistic transactivation of the LPS response element in Drosophila Schneider cells by coexpression of c-Fos, c-Jun, c-Rel, and p65 or c-Jun and p65 required the transactivation domains of c-Jun and p65. These data indicated that c-Fos/c-Jun, c-Rel/p65, and Sp1 regulate TF gene expression in human monocytic cells.
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PMID:Regulation of the tissue factor gene in human monocytic cells. Role of AP-1, NF-kappa B/Rel, and Sp1 proteins in uninduced and lipopolysaccharide-induced expression. 908 93

Nitric oxide (NO) synthesis is upregulated during chronic hepatic inflammation. The present study characterized the mechanisms involved in the induction of NO production and inducible NO synthase (iNOS) messenger RNA (mRNA) expression in murine embryonic liver cell line, BNL CL.2 cells. No production by BNL CL.2 cells was induced by interferon-r (IFN-r) plus lipopolysaccharide (LPS). However, other inflammatory cytokines such as interleukin (IL)-beta, tumor necrosis factor alpha (TNF-alpha), and IL-6 had no additional effects on it. The stimulatory effects of IFN-r and LPS were time- and dose-dependent. NO secretion was inhibited by treatment with inducible NOS inhibitors such as NG-monomethyl L-arginine, NG-amino-L-arginine, and diphenylene iodonium. iNOS mRNA was induced 3 hours after IFN-r plus LPS treatment, and iNOS expression was maximal in the presence of IFN-r and LPS. The protein tyrosine kinase inhibitors such as genistein and tyrphostin reduced IFN-r plus LPS-induced iNOS mRNA expression and NO production. In contrast, the inhibitors of protein kinase C, protein kinase A, and protein phosphatases did not affect iNOS expression induced by IFN-r plus LPS. In addition, iNOS mRNA expression was completely blocked by treatment with tyrphostin. However, mRNA expression of an early response gene, JunB, and constitutively expressed genes beta-actin and GAPDH were not inhibited by tyrphostin. Furthermore, tyrphostin inhibited the promoter activation of iNOS gene induced by IFN-gamma plus LPS, and it also suppressed IFN-gamma plus LPS-induced nuclear factor-kappa B-binding activity but not AP-1-binding activity. These results suggest that NO production and iNOS mRNA expression in this cell line is dependent on protein tyrosine kinases but does not require protein kinase C, protein kinase A, or protein phosphatases.
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PMID:Roles of tyrosine kinases in the regulation of nitric oxide synthesis in murine liver cells: modulation of NF-kappa B activity by tyrosine kinases. 909 97

All the angiotensin peptides originate from angiotensinogen, a glycoprotein synthesized by several tissues, including the brain and the anterior pituitary. In the rat, immunohistochemistry has been used to localize angiotensinogen in gonadotropes and in uncharacterized cells surrounding sinusoids. Both cell types are capable of secreting angiotensinogen in cell culture; only the gonadotropes contain angiotensin II (AngII) and are capable of secreting it in culture. It has been asserted that the perisinusoidal cells are the only source of angiotensinogen for the generation of AngII by gonadotropes. Our current data favor the existence of a complete intracellular renin-angiotensin system (RAS) in gonadotropes and a separate extracellular system which utilizes the high concentration of angiotensinogen from perisinusoidal cells. Furthermore, we postulate that gonadotrope AngII serves mainly reproductive functions, while the proximity of angiotensinogen-secreting cells to folliculostellate cells, and their access to the intercellular sinusoidal and follicular spaces, places the extracellular RAS in a strategic position to affect pituitary growth and the mediation of acute-phase immune responses. In the rat brain, angiotensinogen is expressed by the 16-18th day of fetal life and by areas generally concerned with vasopressor, electrolyte, and fluid homeostasis. Antisense deoxyoligonucleotides to angiotensinogen mRNA lower blood pressure in hypertensive rats and inhibit in vitro growth of neuroblastoma cells, indicating a significant role for angiotensinogen in mitogenic and homeostatic functions. It is commonly agreed that astrocytes express angiotensinogen. Neuronal angiotensinogen has also been demonstrated by immunohistochemistry, as a secretion from neuronal cell cultures, and by reverse-transcriptase polymerase chain reaction. The fate of secreted astrocytic and neuronal angiotensinogen remains obscure. Angiotensinogen is regulated in a tissue-specific manner with smaller or absent responses observed for brain tissue. By using astrocyte and neuronal cultures the actions on angiotensinogen production of growth hormone, IGF-1, inflammatory lipopolysaccharide, and phorbol ester have been examined. Recent observations show that angiotensinogen is regulated positively or negatively by glucocorticoids and that a positive synergism between cAMP and glucocorticoids exists. On the basis of analogous systems for other proteins, a scheme involving glucocorticoid receptors, CREB, and AP-1 transcription factors is formulated to explain glucocorticoid-cAMP interactions. These transcriptional interactions may form a significant functional link between the RAS and adrenergic mechanisms.
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PMID:Novel perspectives on pituitary and brain angiotensinogen. 910 Dec 59

Paclitaxel can induce tumor necrosis factor (TNF) and interleukin-1 gene expression, similar to lipopolysaccharides. Since lipopolysaccharide-induced expression of TNF is related to activation of NF-kappaB, we determined whether NF-kappaB could be activated by paclitaxel. In the human lung adenocarcinoma cell line A549, paclitaxel activated NF-kappaB in a dose-dependent manner with maximal activation after 2-4 h. Since paclitaxel could up-regulate TNF and interleukin-1 secretion and subsequent NF-kappaB activation could be caused by these cytokines, the effect of two other groups of anticancer drugs including vinca alkaloids (vinblastine and vincristine) and anthracyclines (daunomycin and doxorubicin), neither of which induce TNF or interleukin-1 gene expression, were examined. Like paclitaxel, vinblastine, vincristine, daunomycin, and doxorubicin each caused activation of NF-kappaB. Therefore, it is unlikely that activation of NF-kappaB caused by these agents or by paclitaxel is mediated via cytokine up-regulation. Furthermore, actinomycin D and cycloheximide, inhibitors of transcription and translation, respectively, did not inhibit paclitaxel-induced NF-kappaB activation. Several other transcription factors such as AP-1, AP-2, CREB, SP-1, or TFIID were not activated by antineoplastic agents demonstrating specificity of NF-kappaB activation. The involvement of both subunits in the NF-kappaB DNA binding complex was demonstrated by its abrogation by anti-p65 and by supershift by anti-p50 antibodies. Since protein phosphorylation is implicated in the activation of NF-kappaB, the effect of anticancer drugs on protein kinase C activity was measured. Vincristine, daunomycin, and paclitaxel significantly increased protein kinase C activity, and vinblastine and doxorubicin caused similar trends. Following treatment with antineoplastics (1-4 h), cytoplasmic IkappaBalpha degradation occurred concomitantly with translocation of p65 to the nucleus. Specific protein kinase C inhibitors (bisindolylmaleimide (GF109203X) and calphostin C) blocked the activation of NF-kappaB by each compound. Hence, protein kinase C activation may contribute to NF-kappaB activation by antineoplastic agents.
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PMID:Activation of NF-kappaB by antineoplastic agents. Role of protein kinase C. 916 62

Paclitaxel (Taxol) is a novel chemotherapeutic drug that is effective against breast and ovarian cancers. Although the primary target of paclitaxel is microtubules, its efficacy exceeds that of conventional microtubule-disrupting agents, suggesting that it may have additional cellular effects. Previously, we demonstrated that paclitaxel can induce interleukin-8 (IL-8) gene expression at the transcriptional level in subsets of human ovarian cancer lines. In this as well as the previous report, we present evidence that this ability is not linked to the lipopolysaccharide pathway of IL-8 gene induction. The present study identifies the cis-acting elements and trans-acting factors involved in this induction by transfecting DNA constructs containing the 5'-flanking region of the IL-8 gene linked to the chloramphenicol acetyltransferase reporter gene into paclitaxel-responsive and nonresponsive ovarian cancer cells (responsiveness refers to the IL-8 response). Paclitaxel only activated the IL-8 promoter in responsive cells. The AP-1 and NF-kappaB binding sites in the IL-8 promoter are required for activation by paclitaxel; in contrast, a C/EBP site required for IL-8 promoter activation in other cell types is not involved. Gel shift assays demonstrate that paclitaxel causes a marked increase in protein binding to the NF-kappaB and AP-1 consensus binding sequences in the paclitaxel-responsive ovarian cells, but not the nonresponsive cells. The induction of NF-kappaB and AP-1 binding is reduced by the addition of protein kinase C inhibitors and cyclic AMP effector, respectively. These results demonstrate a molecular mechanism for cell-specific paclitaxel-induced IL-8 gene expression which may have clinical relevance.
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PMID:Identification of tumor-specific paclitaxel (Taxol)-responsive regulatory elements in the interleukin-8 promoter. 927 87

Caprine arthritis encephalitis virus (CAEV) is a lentivirus of goats that leads to chronic mononuclear infiltration of various tissues, in particular, the radiocarpal joints. Cells of the monocyte/macrophage lineage are the major host cells of CAEV in vivo. We have shown that infection of cultured goat macrophages with CAEV results in an alteration of cytokine expression in vitro. Constitutive expression of interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) was increased in infected macrophages, whereas transforming growth factor beta1 (TGF-beta1) mRNA was down-regulated. When macrophages were infected with a CAEV clone lacking the trans-acting nuclear regulatory gene tat, IL-8 and MCP-1 were also increased. No significant differences from cells infected with the wild-type clone were observed, suggesting that Tat is not required for the increased expression of IL-8 and MCP-1 in infected macrophages. Furthermore, infection with CAEV led to an altered pattern of cytokine expression in response to lipopolysaccharide (LPS), heat-killed Listeria monocytogenes plus gamma interferon, or fixed cells of Staphylococcus aureus Cowan I. In infected macrophages, tumor necrosis factor alpha, IL-1beta, IL-6, and IL-12 p40 mRNA expression was reduced in response to all stimuli tested whereas changes in expression of granulocyte-macrophage colony-stimulating factor depended on the stimulating agent. Electrophoretic mobility shift assays demonstrated that, in contrast to effects of human immunodeficiency virus infection of macrophages, CAEV infection had no effect on the level of constitutive nuclear factor-kappaB (NF-kappaB) activity or on the level of LPS-stimulated NF-kappaB activity, suggesting that NF-kappaB is not involved in altered regulation of cytokine expression in CAEV-infected cells. In contrast, activator protein 1 (AP-1) binding activity was decreased in infected macrophages. These data show that CAEV infection may result in a dysregulation of expression of cytokines in macrophages. This finding suggests that CAEV may modulate the accessory functions of infected macrophages and the antiviral immune response in vivo.
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PMID:Caprine arthritis encephalitis virus dysregulates the expression of cytokines in macrophages. 931 28

The CD11c/CD18 integrin binds lipopolysaccharide, fibrinogen, and heparin, and mediates leukocyte adhesion, spreading, and migration. CD11c/CD18 is primarily found on myeloid cells and its expression is regulated during myeloid differentiation by transcriptional mechanisms acting on the CD11c gene promoter. We now describe that CCAAT/enhancer-binding proteins (C/EBP) contribute to the basal, tissue-specific and developmentally regulated activity of the CD11c promoter. A C/EBP-binding site within the CD11c promoter (CEBP-80) is bound by CEBPalpha in undifferentiated U937 cells and by C/EBPalpha- and C/EBPbeta-containing dimers in phorbol 12-myristate 13-acetate-differentiating cells, and its disruption decreased the CD11c promoter activity in a cell type-dependent manner. C/EBPalpha transactivated the CD11c promoter through the CEBP-80 element, and C/EBPalpha transactivation was also dependent on the Sp1-70- and Sp1-120 Sp1-binding sites. The -90/-50 fragment from the CD11c promoter, containing the adjacent CEBP-80, Sp1-70, and AP1-60 sites, differentially enhanced the activity of the minimal prolactin promoter in hematopoietic and epithelial cells. Altogether, these results demonstrate that C/EBP factors participate in the tissue-restricted and regulated expression of the CD11c/CD18 integrin through functional interactions with Sp1, suggest that Sp1-related factors modulate C/EBPalpha transcriptional activity on the CD11c promoter, and demonstrate the existence of a composite regulatory element recognized by C/EBP, Sp1, and AP-1 factors and whose enhancing effects are cell-type dependent.
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PMID:CCAAT-enhancer-binding proteins (C/EBP) regulate the tissue specific activity of the CD11c integrin gene promoter through functional interactions with Sp1 proteins. 936 Sep 88

Binding of plasma factor VII(a) to tissue factor (TF) initiates the coagulation cascade. In health, TF is not expressed in endothelial cells. However, endothelial cells express TF in response to lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF alpha), and other biological stimuli. TF expression by endothelial cells is implicated in thrombotic disorders in patients with a variety of clinical disorders. In the present study, we demonstrate that curcumin (diferulolylmethane), a known anticarcinogenic and anti-inflammatory agent, inhibited phorbol 12-myristate 13-acetate (PMA), LPS, TNF alpha, and thrombin-induced TF activity and TF gene transcription in human endothelial cells. The present data show that curcumin prevented the activation of c-Rel/p65, which is essential for TF gene activation in endothelial cells, by impairing the proteolytic degradation inhibitor protein, I kappa B alpha. The data also show that curcumin downregulated AP-1 binding activity. The present studies are the first to demonstrate that PMA, but not LPS, TNF alpha, and thrombin, induced Egr-1 binding to the second serum-responsive region (SRR-2) of TF promoter and that curcumin inhibited the PMA-induced Egr-1 binding to SRR-2. Overall, the data suggest that the anticarcinogenic and anti-inflammatory properties of curcumin may be related to its ability to inhibit cellular gene expression regulated by transcription factors NF-kappa B, AP-1, and Egr-1.
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PMID:Inhibition of tissue factor gene activation in cultured endothelial cells by curcumin. Suppression of activation of transcription factors Egr-1, AP-1, and NF-kappa B. 943 86

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