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)

After infection in utero or at birth with a cell culture adapted strain of mouse cytomegalovirus (MCMV), several mouse strains developed a latent virus infection in the presence of specific antiviral antibodies. Up to 5 mo after infection, MCMV could be activated and recovered from spleen lymphocytes of the infected animals that were co-cultivated with histoincompatible (H-2 foreign) mouse embryo cells from uninfected animals. In contrast, co-cultivation of lymphoid cells from infected mice with mouse embryo cells from syngeneic, histocompatible (H-2 similar) donors did not activate MCMV. Similarly, MCMV was not recovered from sonicated lymphoid cells. Virus was activated by treating viable lymphoid cells with lipopolysaccharide, a B-cell mitogen, but was not activated by a variety of other mitogens such as phytohemagglutinin, concanavalin A, or pokeweed mitogen. Subsequent purification of lymphoid cells from the infected mice by a variety of techniques indicated that MCMV was harbored in the B-lymphocyte population.
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PMID:Pathogenesis of of cytomegalovirus infection. I. Activation of virus from bone marrow-derived lymphocytes by in vitro allogenic reaction. 16 87

An animal model of a sublethal infection, utilizing murine cytomegalovirus (MCMV), was developed to determine whether immunological factors could contribute to the establishment of a persistent viral infection. Adult female C3H mice inoculated intraperitoneally with 10(5) plaque-forming units of MCMV developed splenomegaly 5 to 12 days after infection. Virus replicated to peak titers (10(3) to 10(6) plaque-forming units per g of tissue) in liver, spleen, lung, kidney, and salivary gland tissue during the acute phase of the infection (3 to 12 days); it then decreased to undetectable levels in all tissues except salivary gland. Serum interferon was detected as early as 12 h after infection, peaked at 36 h (1,093 U/ml), and was undetectable by 4 days after infection. MCMV-infected animals were hyporeactive to interferon induction with New castle disease virus on days 5 to 9 of the infection. Splenic lymphocyte reactivity to phytohemagglutinin and lipopolysaccharide was normal early during the course of the infection, was suppressed during the acute phase of the infection, and had returned to normal by day 18. These data indicate that several parameters of host defense are transiently suppressed during the course of a MCMV infection. The capacity of cytomegaloviruses to alter host resistance may be one factor that contributes to the establishment of a persistent infection.
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PMID:Alteration of host defense mechanisms by murine cytomegalovirus infection. 20 66

The effects on some host defenses of murine cytomegalovirus (MCMV) and(or) EL(4), a mouse ascites homograft, were studied in mice. Assays of cellular and humoral immunity in response to either or both of these perturbations were carried out by quantitation of various immune activities.Limited studies demonstrated no effect of EL(4) inoculation on the host response to MCMV by organ viral titer, duration of viral persistence, or anti MCMV complement-fixing antibody titer. Prior infection with MCMV, however, resulted in greatly reduced numbers of splenocytes, the source in this study of immune effector cells. Residual splenocytes demonstrated less response to both phyto-hemagglutinin and lipopolysaccharide, particularly in the 2-3-wk interval after infection. Similarly, responder cells in mixed lymphocyte cultures were less reactive when derived from infected animals. Lymphocyte-mediated cytolysis of EL(4) was significantly less in mice infected on the day of and 7, 14, and 21 days before the tumor homograft with a return to control levels by 28 days. 90% of the cell-mediated cytolysis could be eliminated by treatment with anti-theta serum. Serum-mediated cytolysis of EL(4) was also reduced in infected animals. No suppressor cells or serum inhibitory factors could be identified in infected animals. Although alternative explanations exist, this study suggests that in infected animals there is a significant reduction in both the number and function of bone marrow-derived and thymus-derived cells directed against the alloantigens in EL(4).
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PMID:Viral infection-homograft interactions in a murine model. 21 27

The purpose of this study was to compare the effects of murine cytomegalovirus infection introduced after an EL4 ascites tumor allograft with cytomegalovirus infection accompanying or preceding the allograft. Parameters that were measured included documentation to the host's immune system. Depressed immune response of splenocytes from mice infected at any time before assay was documented by decreased responsiveness to phytohemagglutinin, to lipopolysaccharide, and to an alloantigen in mixed lymphocyte culture. In contrast, animals infected after grafting had enhanced lymphocyte-mediated cytolysis (LMC), enhanced serum-mediated cytolysis (SMC), and larger spleens than did animals that were only grafted and animals that were infected before grafting. Neither a depressive nor an enhancing effect of virus administered after grafting was reflected in vivo in reduced or increased graft clearance. Nonspecific effects of virus increased LMC and SMC in vitro, but the primary effect of viral infection after grafting is immune depression.
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PMID:Effects of murine cytomegalovirus infection on the immune response to a tumor allograft. 23 71

We have developed a sensitive genetic assay to analyze DNA sequences and regulatory elements required for immunoglobulin heavy chain isotype switch recombination. Recombination substrates containing mu and gamma 3 chain switch (S)-region sequences, S mu and S gamma 3, are transiently introduced into primary murine B cells cultured with lipopolysaccharide to induce isotype switching. Recombination involving S-region sequences deletes a conditionally lethal marker, the leftward promoter of phage lambda (lambda PL), enabling recovered plasmids to transform Escherichia coli. In substrates carrying S mu-lambda PL-S gamma 3, about 2% of replicated molecules undergo deletion of lambda PL during transfection; insertion of either the immunoglobulin heavy chain promoter and enhancer sequences or cytomegalovirus IE1 promoter region upstream of S mu increases recombination 10-fold or more to 25% of replicated molecules. Guanosine-rich S-region sequences are essential for efficient recombination of these substrates.
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PMID:Transcriptional regulatory elements stimulate recombination in extrachromosomal substrates carrying immunoglobulin switch-region sequences. 131 54

We document suppression of tumor necrosis factor alpha (TNF-alpha)-associated cytotoxic activity in a human monocytic cell line (THP-1) infected with the mycoplasma free human cytomegalovirus (CMV) strain AD169. Addition of lipopolysaccharide (LPS) to cell cultures that had been infected with CMV for 24 h resulted in a significant reduction in released cytotoxic activity to mouse L929 cells at 3-22 h post-LPS compared with mock-infected cultures. However, using an ELISA to measure TNF-alpha antigen levels in these culture supernatants, we found infected cultures had significantly higher TNF-alpha antigen levels than in mock-infected cultures following LPS induction. CMV alone also induced TNF-alpha release and possibly TNF-alpha inhibitor(s) which may have blocked TNF-alpha associated cytotoxic activity in CMV-infected THP-1 cell culture supernatants.
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PMID:Suppression of LPS-inducible cytotoxicity in cytomegalovirus-infected THP-1 monocytic cell cultures does not correlate with a decrease in TNF-alpha antigen. 133 75

Prointerleukin 1 beta (IL-1 beta) is a cytokine that mediates a broad range of biological activities. Genomic sequences that regulate IL-1 beta transcription include both inducible regulatory elements located more than 2,700 bp upstream of the transcriptional start site (cap site) and proximal elements located near the TATA box of this gene. In this study, we focused on the identification and characterization of trans-acting nuclear regulatory proteins that bind to the cap site-proximal region of the human IL-1 beta gene. We identified a protein, termed NFIL-1 beta A (NF beta A), that binds to a highly conserved 12-bp DNA sequence (-49 to -38) located upstream of the TATA box motif in both the human and murine IL-1 beta genes. The IL-1 alpha gene, which lacks a TATA motif, does not possess an NF beta A-binding sequence within the promoter region, suggesting that NF beta A may selectively regulate IL-1 beta expression. Using electrophoretic mobility shift assays, we identified several distinct DNA-protein complexes that are expressed in a cell-type-specific manner. In monocytic cell lines, the relative abundance of these complexes varies rapidly following stimulation of the cells with phorbol esters or lipopolysaccharide. UV cross-linking analysis identified two distinct DNA-binding polypeptides that comprise distinct complexes. The functional role of NF beta A was assessed in transient transfection assays. These data indicate that NF beta A is required for both basal and inducible promoter activity in monocytic cells. Furthermore, the human cytomegalovirus immediate-early 1 gene product requires the presence of NF beta A in order to trans-activate the proximal IL-1 beta promoter in a monocytic cell line. We propose that NF beta A is a factor that mediates either direct or indirect activation by the immediate-early 1 gene product. The proximity of this essential factor to the TATA motif suggests a possible role in transcriptional initiation.
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PMID:The functional importance of a cap site-proximal region of the human prointerleukin 1 beta gene is defined by viral protein trans-activation. 163 Apr 55

Treatment of mice with cyclophosphamide causes immunosuppression and an enhancement of murine cytomegalovirus infection. In chemotherapy experiments, animals received cyclophosphamide (100 mg/kg by intraperitoneal [ip] injection) every 3-4 days starting 1 day before viral challenge. Once-daily ip treatments with ganciclovir (12.5, 25, and 50 mg/kg) for 5 or 10 days starting 24 h after viral challenge delayed but did not prevent death. In each case the animals died 8-12 days after the last dose of drug was given. Murine cytomegalovirus titers in tissues were suppressed during ganciclovir treatments but rose with discontinuation of therapy. Concanavalin A (T cell blastogenic) responses and, to a lesser extent, lipopolysaccharide (B cell blastogenic) responses were increased in ganciclovir-treated mice compared with the placebo group. Because of the progressive nature of the infection after termination of drug treatment, this model mimics the situation encountered in AIDS patients. The cyclophosphamide model will be useful to study drug treatment regimens.
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PMID:Progressive murine cytomegalovirus disease after termination of ganciclovir therapy in mice immunosuppressed by cyclophosphamide treatment. 165 60

To clarify which cytokines could potentially be produced by astrocytes, we have assessed the presence of mRNA for a number of cytokines in astrocyte-enriched brain cultures. The cultures were derived from neonatal murine brain and were treated with either interferon-gamma, lipopolysaccharide or tumor necrosis factor-alpha, or infected with murine cytomegalovirus. RNA was extracted at 0, 4, 24 and 48 hours post treatment. A DNA copy of total cytoplasmic RNA was synthesised and specific cDNA amplified using the polymerase chain reaction and detected by hybridization with specific probes. The following cytokines were studied: IL3, IL4, IL6, TNF alpha, TGF beta, LIF, G-CSF, M-CSF and GM-CSF. Transcripts for TGF beta, IL6, LIF and M-CSF were present constitutively but increased with stimulation, whereas transcripts for TNF alpha, IL6, GM-CSF, G-CSF and LIF were detected only after stimulation. Messenger RNA for IL3 and IL4 was not detected. The magnitude and kinetics of the induction varied according to the cytokine and the stimulus. These results indicate the possibility of intra-cerebral production of a number of cytokines that may play a role in the clearance of viral or bacterial pathogens and in the generation of neuropathology.
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PMID:Detection of cytokine mRNA in astrocyte cultures using the polymerase chain reaction. 216 30

The immediate early (IE) genes of human cytomegalovirus (HCMV) can be expressed in monocytes/macrophages and are known to regulate other viral genes. The purpose of these studies was to determine if HCMV IE gene products also modulate expression of a monocyte/macrophage-derived gene, interleukin 1 (IL-1) beta. Steady-state cell-derived IL-1 beta mRNA was increased in lipopolysaccharide (LPS)-stimulated THP-1 cells when transfected with the HCMV IE1 + 2 genes, when compared to cells transfected with a control DNA. LPS-stimulated THP-1 cells also exhibited approximately 30-fold higher IL-1 CAT activity when cotransfected with IE1 + 2 than was observed for the same cells cotransfected with IL-1 CAT and a control plasmid containing the IE promoter alone. LPS increased IL-1 CAT activity in the absence of HCMV genes only twofold. IE1, by itself, increased IL-1 CAT activity in LPS-stimulated cells, whereas, IE2, by itself, caused no change in IL-1 CAT activity. These studies show that the IE1 gene of HCMV can regulate IL-1 beta gene expression. The observations further suggest that some of the inflammatory processes associated with HCMV infection may be due to an effect of HCMV IE genes on cell-derived genes, such as the IL-1 beta gene.
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PMID:Modulation of interleukin 1 beta gene expression by the immediate early genes of human cytomegalovirus. 216 30


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