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

Interleukin 4 (IL-4) can induce the expression of IgG1 in sIgG- murine B cells stimulated with mitogens or through a cognate interaction with T helper (Th) cells. We have investigated the molecular basis for the IL-4-induced switch to IgG1 in lipopolysaccharide (LPS)-stimulated murine B cells and have previously shown that IL-4 induces transcription of the gamma 1 switch region before switch recombination. We now demonstrate that IL-4 induces a DNase I hypersensitive site at the 5' end of the gamma 1 switch region in resting B cells. LPS is not required, but it enhances induction. Hence, the interaction of IL-4 with its receptor results in increased accessibility of the gamma 1 switch region. The more open chromatin structure and increased transcriptional activity may be important in the selection of this region for switch recombination.
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PMID:Interleukin 4 induces changes in the chromatin structure of the gamma 1 switch region in resting B cells before switch recombination. 235 83

Class II (Ia) major histocompatibility complex molecules are cell surface proteins normally expressed by a limited subset of cells of the immune system. These molecules regulate the activation of T cells and are required for the presentation of antigens and the initiation of immune responses. The expression of Ia in B cells is determined by both the developmental stage of the B cell and by certain external stimuli. It has been demonstrated previously that treatment of B cells with lipopolysaccharide (LPS) results in increased surface expression of Ia protein. However, we have confirmed that LPS treatment results in a significant decrease in mRNA encoding the Ia proteins which persists for at least 18 h. Within the upstream regulatory region of A alpha k, an NF-kappa B-like binding site is present. We have identified an LPS-induced DNA-binding protein in extracts from athymic mice whose spleens consist predominantly of B cells. Binding activity is present in low levels in unstimulated spleen cells and is increased by LPS treatment. This protein binds to two sites in a regulatory region of the Ia A alpha k gene, one of which contains the NF-kappa B-like binding site. DNA fragments containing these sites cross-compete for protein binding. Analysis by DNase I footprinting identified a target binding sequence, named the LPS-responsive element. Although this target sequence contains an NF-kappa B-like binding site, competition with a mutant oligonucleotide demonstrated that bases critical for NF-kappa B binding are not required for binding of the LPS-inducible protein. Therefore, we hypothesized that this inducible protein represents a new mediator of LPS action, distinct from NF-kappa B, and may be one mechanism to account for the decrease in mRNA encoding the Ia proteins.
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PMID:A lipopolysaccharide-induced DNA-binding protein for a class II gene in B cells is distinct from NF-kappa B. 247 82

Transcription of unrearranged kappa constant region (kappa 0) loci is dramatically induced in pre-B cells transformed by the Abelson murine leukemia virus when the cells are exposed to bacterial lipopolysaccharide (LPS). Transcriptional activity, detected both by accumulation of the 8-kilobase kappa 0 RNA product and by nuclear run-on measurements, is evident within a few hours after exposure to LPS and continues to increase over a 24-hr period. During this time, transcription of rearranged mu heavy-chain loci remains at the basal constitutive level. In accord with previous studies of the B-cell lymphoma 70Z/3, this transcriptional activation is accompanied by the appearance of a DNase I-hypersensitive site in the kappa enhancer region but not by any detectable hypomethylation of the locus. Moreover, the present studies demonstrate that induction of kappa transcription can occur in the absence of DNA or protein synthesis. These results have led us to propose a model in which an external signal such as LPS or a functionally equivalent lymphokine may initiate kappa transcription in pre-B cells by modifying or overriding the activity of an enhancer-specific factor.
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PMID:Inducible transcription of the unrearranged kappa constant region locus is a common feature of pre-B cells and does not require DNA or protein synthesis. 392 1

Transcription of the vascular cell adhesion molecule-1 (VCAM-1) gene in endothelial cells is induced by the inflammatory cytokines interleukin-1 beta, tumor necrosis factor-alpha, and lipopolysaccharide. Previous studies demonstrated that the cytokine-response region in the VCAM1 promoter contains binding sites for the transcription factors nuclear factor-kappa B (NF-kappa B) and interferon regulatory factor-1. Using a saturation mutagenesis approach, we report that the cytokine-inducible enhancer consists of these previously characterized elements and a novel region located 3' of the NF-kappa B sites. Electrophoretic mobility shift assays and DNase I footprint studies with endothelial nuclear extracts and recombinant protein revealed that the transcriptional activator Sp1 interacts with this novel element in a specific manner. Transient transfection assays using vascular endothelial cells revealed that site-directed mutations in the Sp1 binding element decreased tumor necrosis factor-alpha-induced activity of the VCAM1 promoter. The cytokine-induced enhancer of the VCAM1 gene requires constitutively bound Sp1 and induced heterodimeric NF-kappa B for maximal promoter activity.
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PMID:Sp1 is a component of the cytokine-inducible enhancer in the promoter of vascular cell adhesion molecule-1. 749 19

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 chicken lysozyme locus is regulated in oviduct and macrophages by a complex set of well-characterized cis-regulatory DNA elements. We determined the DNase I hypersensitive chromatin site pattern of the chromatin of the lysozyme locus in retrovirally transformed cell lines representing different stages of myelomonocytic cell differentiation. In the transformed multipotent progenitor stage and in erythroblasts, only a DNase I hypersensitive chromatin site at a silencer element located -2.4 kb upstream of the transcriptional start site is present. At the myeloblast stage DNase I hypersensitive chromatin sites are formed both at the distal enhancer located at -6.1 kb and at the promoter. Later in differentiation, at the monocytic stage, a second DNase I hypersensitive chromatin site appears at the medial enhancer located at -2.7 kb. Parallel with DNase I hypersensitive chromatin site formation at the medial enhancer, the DNase I hypersensitive chromatin site at the silencer element disappears. These chromatin rearrangements correlate with the mRNA expression of the gene that is undetectable in multipotent progenitors and maximal in a lipopolysaccharide-stimulated monocyte cell line. Our results show that the chromatin structure and the transcriptional activity of the gene are tightly coupled during commitment and maturation of the myelomonocytic lineage.
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PMID:Dynamic changes in the chromatin of the chicken lysozyme gene domain during differentiation of multipotent progenitors to macrophages. 774 89

Regulatory elements important for transcription of the murine interleukin-1 beta (IL-1 beta) gene lie within a DNase I-hypersensitive region located > 2,000 bp upstream from the transcription start site. We have identified within this region a novel positive regulatory element that is required for activation of an IL-1 beta promoter-chloramphenicol acetyltransferase (CAT) fusion gene in the murine macrophage line RAW264.7. Electrophoretic mobility shift analysis of the 3' portion (-2315 to -2106) of the hypersensitive region revealed at least two nuclear factor binding sites, one of which is located between positions -2285 and -2256. Competitive inhibition studies localized the binding site to a 15-bp sequence between -2285 and -2271. Nuclear factor binding was lost by mutation of the 6-bp sequence from -2280 to -2275. The specific retarded complex formed with RAW264.7 nuclear extract was not detected under similar conditions with nuclear extracts from RLM-11, a murine T-cell line which does not express IL-1 beta RNA. Mutation of the 6-bp sequence (-2280 to -2275) in the chimeric IL-1 beta promoter -4093 +I CAT plasmid virtually eliminated the activation of this reporter gene by lipopolysaccharide (LPS) in transfected RAW264.7 cells. Multimerization of the 15-bp sequence containing the core wild-type 6-bp sequence 5' of minimal homologous or heterologous promoters in CAT reporter plasmids resulted in significant enhancement of CAT expression compared with parallel constructs containing the mutant 6-bp core sequence. This element was LPS independent and position and orientation dependent. The multimerized 15-bp sequence did not enhance expression in RLM-11 cells. Methylation interference revealed contact residues from -2281 to -2271, CCAAAAAGGAA. Because a search of the NIH TFD data bank with the 11-bp binding site sequence found no homology to known nuclear factor binding sites, we have designated this sequence the IL1 beta -upstream nuclear factor 1 (IL1 beta -UNF1) target. UV cross-linking and sodium dodecyl sulfate-polyacrylamide electrophoresis identified an IL1 beta -UNF1-specific binding factor approximately 85 to 90 kDa in size.
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PMID:A novel cis-acting element required for lipopolysaccharide-induced transcription of the murine interleukin-1 beta gene. 779 17

Tissue factor, the cellular receptor for factor VII/VIIa, activates both the intrinsic and extrinsic pathways of blood coagulation. In this analysis we have used DNase I footprinting to map the sites of protein-DNA interaction along the promoter (-383 to +8) using nuclear extracts prepared from uninduced and lipopolysaccharide-induced THP-1 cells. We have identified six regions that interact with nuclear factors in both uninduced and induced extracts. Four footprints are contained within a region reported to confer base-line high level expression and lipopolysaccharide and serum induction. Two additional footprints map to a region reported to reduce basal transcription by 50%. The only qualitative change in the footprint pattern with uninduced and induced extracts is the appearance of two hypersensitive sites with uninduced extracts. In addition, changes in the level of protein- DNA binding are detected with only one probe by DNA mobility shift analysis. A combination of well characterized transcription factors (AP1), primarily lymphoid cell specific regulatory proteins (NF-kappa B- and/or Ets-1-related proteins), as well as additional, uncharacterized proteins appear to interact with these sequences. Our data suggest that post-translational modification of existing transcription factors, and not induction of new DNA-binding activity, mediates the lipopolysaccharide induction of tissue factor synthesis in THP-1 cells.
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PMID:Lipopolysaccharide induction of tissue factor expression in THP-1 monocytic cells. Protein-DNA interactions with the promoter. 828 2

These studies examine the molecular basis for increased transcription of tissue factor (TF) in THP-1 cells stimulated with lipopolysaccharide (LPS). DNase I footprinting identified six sites of protein-DNA interaction between -383 and the cap site that varied between control and induced extracts. Four footprints show qualitative differences in nuclease sensitivity. Footprints I (-85 to -52) and V (-197 to -175) are induction-specific and localize to regions of the promoter that mediate serum, phorbol ester, partial LPS response (-111 to +14), and the major LPS-inducible element (-231 to -172). Electrophoretic mobility shift assays with the -231 to -172 probe demonstrate JunD and Fos binding in both control and induced nuclear extracts; however, binding of c-Jun is only detected following LPS stimulation. Antibody inhibition studies implicate binding of Ets-1 or Ets-2 to the consensus site between -192 and -177, a region that contains an induction-specific footprint. The proximal region (-85 to -52), containing the second inducible footprint, binds Egr-1 following induction. These data suggest that LPS stimulation of THP-1 cells activates binding of c-Jun, Ets, and Egr-1 to the TF promoter and implicates these factors in the transcriptional activation of TF mRNA synthesis.
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PMID:Lipopolysaccharide induction of THP-1 cells activates binding of c-Jun, Ets, and Egr-1 to the tissue factor promoter. 864 47


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