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)

The synthesis and secretion of several acute-phase proteins increases markedly following physiological stress. alpha 1-Acid glycoprotein (AGP), a major acute-phase reactant made by the liver, is strongly induced by inflammatory agents such as lipopolysaccharide (LPS). Nuclear run-on assay showed a 17-fold increase in the rate of AGP transcription 4 h following LPS injection. DNase I footprinting assays revealed multiple protein binding domains in the mouse AGP-1 promoter region. Region B (-104 to -91) is protected by a liver-enriched transcription factor that is heat labile and in limiting quantity. An adjacent region, C (-125 to -104), is well-protected by nuclear extracts from hepatocytes. Electrophoretic mobility shift assays indicated that only one DNA-protein complex can form with an oligonucleotide corresponding to region B. However, nuclear proteins from untreated mouse liver can form three strong complexes (C1, C2, and C3) and a weak one (C4) with oligonucleotide C. An acute-phase-inducible DNA-binding protein (AP-DBP) forms complex 4. A dramatic increase (over 11-fold) in AP-DBP binding activity is seen with nuclear proteins from LPS-stimulated animals. Interestingly, AP-DBP, a heat-stable factor, can form heterodimers with the transcription factor CCAAT/enhancer binding protein (C/EBP). Furthermore, purified C/EBP also binds avidly to region C. Our studies indicate that several liver-enriched nuclear factors can interact with AGP-1 promoter and that AP-DBP binds to the AGP-1 promoter with high affinity only during the acute-phase induction.
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PMID:Interaction of acute-phase-inducible and liver-enriched nuclear factors with the promoter region of the mouse alpha 1-acid glycoprotein gene-1. 137

Eucaryotic organisms possess natural defense processes triggered by stress factors such as injury, infection, and inflammation. The acute phase response is an early defense mechanism during which striking changes in protein synthesis occur in the liver and other tissues. The altered expression of many acute phase protein genes is at the transcriptional level. Some of these genes have DNA binding sites for the CCAAT/enhancer binding protein (C/EBP) family of transcription factors. We report here that in vivo expression of three isoforms of C/EBP is dramatically changed during the acute phase response. The steady-state mRNA levels of C/EBP alpha decreased significantly in the liver, lung, and fat tissues of lipopolysaccharide (LPS)-treated mice; moreover, nuclear run-off transcription assays indicated a decrease in the rate of C/EBP alpha gene transcription in isolated liver nuclei. The steady-state levels of C/EBP beta and a new isoform, C/EBP delta, were dramatically increased in many tissues within 4 h following LPS treatment. The rates of transcription of these two genes were only minimally altered in liver but significantly increased in kidney nuclei isolated from stimulated animals. Thus, the C/EBP isoforms exhibit differential mechanisms in their responses to LPS in various tissues and are likely to play an important role in mediating the transcriptional activation of genes involved in the acute phase response.
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PMID:Differential expression of three C/EBP isoforms in multiple tissues during the acute phase response. 137 93

The interleukin 6 (IL-6) promoter is rapidly and transiently activated by other cytokines, including IL-1 and tumour necrosis factor (TNF), as well as by phorbol esters and cyclic AMP agonists. Studies using promoter mutants suggested that an IL-1-responsive element mapped within the -180 to -123 region of the IL-6 promoter. A nuclear factor (NF-IL6) that recognized a unique sequence containing an inverted repeat, ACATTGCACAATCT, was identified within the region. Direct cloning of the human NF-IL6 revealed its similarity to C/EBP, a liver- and adipose tissue-specific transcription factor. C/EBP and NF-IL6 recognize the same nucleotide sequence, but exhibit distinct patterns of expression. NF-IL6 is expressed at a low level in normal tissues, but is rapidly and drastically induced by bacterial lipopolysaccharide (LPS) or inflammatory cytokines such as IL-1, TNF and IL-6. Recently, NF-IL6 has been shown to be identical to IL-6DBP, the DNA-binding protein which is responsible for IL-6-mediated induction of several acute-phase proteins. Evidence that NF-IL6 DNA-binding activity is increased after IL-6 stimulation without increased NF-IL6 protein synthesis demonstrates the importance of post-translational modification. There are some results indicating that phosphorylation is involved in transcriptional and binding activities of NF-IL6. Taken together, these findings indicate that NF-IL6 may be an important transcription factor on the signal transduction pathways of IL-1 and IL-6.
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PMID:Regulation of expression of the interleukin 6 gene: structure and function of the transcription factor NF-IL6. 138 54

Granulocyte colony-stimulating factor (G-CSF) is produced from macrophages in response to lipopolysaccharide (LPS). GPE1, a cis-acting element of the G-CSF gene promoter, functioned as an LPS-inducible element. We isolated cDNA and a chromosomal gene encoding the mouse GPE1-binding protein (GPE1-BP). A 150-amino acid protein deduced from the cDNA has a basic domain and a leucine zipper motif, and seems to be identical to that of recently isolated Ig/EBP. The nuclear extract from COS cells transfected with the cDNA showed GPE1-binding activity. Transcripts were ubiquitously detected, and may be spliced from two exons of a single gene.
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PMID:Molecular cloning of cDNA and a chromosomal gene encoding GPE1-BP, a nuclear protein which binds to granulocyte colony-stimulating factor promoter element 1. 170 21

Using a DNA probe from the DNA-binding portion of the NF-IL6 gene and an antibody against the DNA-binding domain of NF-IL6, we isolated a gene homologous to NF-IL6 in the DNA-binding and leucine zipper domains. This intronless gene, termed NF-IL6 beta encodes a 269-amino acid protein with a potential leucine zipper structure, and the gene product can bind to the CCAAT homology as well as the viral enhancer core sequence, as in the cases of NF-IL6 and C/EBP. This gene is expressed at an undetectable or a minor level in normal tissues but is induced by lipopolysaccharide or inflammatory cytokines, as in the case of NF-IL6. NF-IL6 beta easily forms a heterodimer with NF-IL6 in vitro and the heterodimeric complex binds to the same DNA sequence as the respective homodimers. When examined by transient luciferase assays, NF-IL6 beta is consistently a stronger transactivator than NF-IL6. Furthermore, NF-IL6 beta shows a synergistic transcriptional effect with NF-IL6. These data suggest that NF-IL6 beta is an important transcriptional activator in addition to NF-IL6 in regulation of the genes involved in the immune and inflammatory responses.
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PMID:A member of the C/EBP family, NF-IL6 beta, forms a heterodimer and transcriptionally synergizes with NF-IL6. 174 2

AGP/EBP (C/EBP beta) is a key transcription factor responsible for transcriptional induction of many acute-phase protein genes. To characterize the regulation of this gene, we have isolated the mouse genomic DNA and sequenced the 5'-regulatory region. Using nuclear extracts from lipopolysaccharide (LPS)-stimulated or unstimulated mouse liver, three protein factor-binding motifs, UF1(-376 to -352), UF2(-254 to -223), and UF3(-220 to -190), as well as two Sp1 motifs (-309 to -277, and -264 to -241) were identified by DNase I footprinting assays. Biochemical analysis has shown that the AGP/EBP protein can bind to UF1 and UF2 sites, whereas an ubiquitous factor of unknown identity can bind to the UF3 site. Functional characterizations indicate that all of these factors play a major role in AGP/EBP induction. Thus, the agp/ebp gene is autoregulated during the acute-phase response.
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PMID:Autoregulated induction of the acute-phase response transcription factor gene, agp/ebp. 759 8

The interleukin-6 (IL-6) gene expression in bovine monocytes is highly induced following bacterial lipopolysaccharide (LPS) stimulation. To identify the promoter element(s) involved in the inducible transcription of IL-6, a 5'-flanking region containing 230 bp of the bovine IL-6 gene was linked to a reporter gene coding for bacterial chloramphenicol acetyltransferase (CAT) and analyzed for its ability to confer LPS-responsiveness to the reporter CAT gene in monocytic cells. Using mutant reporter genes, we demonstrate that although mutation in the NF-kappa B element produces the major loss of induction, both NF-kappa B and C/EBP elements are necessary for maximal transcriptional activation of the bovine IL-6 gene. Gel electrophoretic mobility-shift assays have detected induced DNA-binding activities in the LPS-stimulated monocytes. Further characterization has revealed the activation and interaction of C/EBP-alpha, C/EBP-beta (NF-IL6), NFKB1 (p50), and RelA (p65) to their specific binding elements present in the bovine IL-6 gene. These results suggest a model in which induction of C/EBP-alpha in differentiating monocytes contributes and synergizes with induced C/EBP-beta and NF-kappa B, which are activated following LPS stimulation, to mediate a high rate of IL-6 transcription under inflammatory conditions.
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PMID:Lipopolysaccharide-mediated induction of the bovine interleukin-6 gene in monocytes requires both NF-kappa B and C/EBP binding sites. 766 56

The promoter region of the rabbit serum amyloid A (SAA) gene contains two adjacent C/EBP and one NF-kappa B binding element. Involvement of these elements in SAA gene induction, following lipopolysaccharide (LPS) stimulation of the liver, has been studied by investigating LPS-activated transcription factors and their interaction with the promoter elements of the SAA gene. Appearance of complexes in the electrophoretic mobility shift assay has indicated that DNA-binding proteins that interact with the NF-kappa B element of the SAA promoter are induced in the LPS-treated rabbit liver. Presence of RelA (p65 subunit of NF-kappa B) in these complexes was demonstrated by the ability of RelA-specific antisera to supershift the DNA-protein complexes. LPS also induced several members of the C/EBP family of transcription factors, which interacted with the C/EBP motifs of the SAA promoter. Activated C/EBP and RelA form a RelA-C/EBP heteromeric complex that associates with varying affinity to NF-kappa B and C/EBP elements of the SAA gene. Transfection assays using both transcription factor genes have demonstrated that the heteromeric complex of NF-kappa B and C/EBP is a much more potent transactivator of SAA expression than each transcription factor alone. The heteromeric complex efficiently promotes transcription from both NF-kappa B and C/EBP sites.
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PMID:Concerted participation of NF-kappa B and C/EBP heteromer in lipopolysaccharide induction of serum amyloid A gene expression in liver. 770 80

Macrophages respond to lipopolysaccharide (LPS) with the activation of various genes, including the lysozyme gene. Here, we show that the level of lysozyme mRNA increases following treatment of chicken myelomonocytic HD11 cells with LPS. By transient and stable transfection of the chloramphenicol acetyltransferase (CAT) gene controlled by regulatory elements of the lysozyme gene, we identified a subfragment of the -6.1 kilobase (kb) lysozyme enhancer that mediates the LPS-induced lysozyme expression. This subfragment contains two elements (D and E), each of which matches the highly degenerate consensus sequence of binding sites for C/EBP-like transcription factors. Furthermore, we found protein complexes to interact with elements D and E whose binding activity to elements D and E is LPS-inducible in myelomonocytic HD11 cells. Immunomobility shift assays show that NF-M, a myeloid-specific C/EBP beta-related transcription factor is an essential component of these protein complexes. Mutations of the C/EBP binding sites within D and E cause a reduction of basal activity and abolish LPS responsiveness of the -6.1 kb lysozyme enhancer. These results show that the -6.1 kb lysozyme enhancer, in addition to its role in cell type-specific expression, can mediate, by interacting with NF-M, LPS-induced expression of the lysozyme gene in chicken myelomonocytic cells.
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PMID:The far upstream chicken lysozyme enhancer at -6.1 kilobase, by interacting with NF-M, mediates lipopolysaccharide-induced expression of the chicken lysozyme gene in chicken myelomonocytic cells. 798 75

C/EBP-related proteins 2 and 3 (CRP2 and CRP3) are differentially expressed by P388 lymphoblasts and their derivative P388D1(IL1) macrophages. We have ectopically expressed CRP2, the predominant CRP in macrophages, in P388 lymphoblasts. The expression of CRP2 is sufficient to confer the lipopolysaccharide (LPS)-inducible expression of interleukin 6 and monocyte chemoattractant protein 1 to lymphoblasts, which normally do not display LPS induction of inflammatory cytokines. Consistent with these findings, the expression of CRP2 antisense RNA blocks the LPS induction of IL-6 expression in P388D1(IL1) macrophages. This work clearly establishes the essential role of CRP2 in the induction of cytokine genes by LPS. Additionally, these data add MCP-1 to the list of cytokines showing an involvement of CRP2 in their expression.
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PMID:C/EBP-related protein 2 confers lipopolysaccharide-inducible expression of interleukin 6 and monocyte chemoattractant protein 1 to a lymphoblastic cell line. 804 85


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