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 effects of bacterial lipopolysaccharide (LPS) on the expression of surface antigens including major histocompatibility complex (MHC) and complement type 3 (CR3) receptors on microglial cells in the corpus callosum in postnatal rat brain were investigated. When LPS was injected intravenously (i.v.) in 1-d-old rats, the immunostaining of callosal amoeboid microglial cells with OX-18 directed against MHC class I antigen was enhanced 24 h after the injection in comparison with the controls. The expression of MHC class II (Ia) antigen on the same cell type as shown by its immunoreactivity with OX-6 was also elicited especially after 2 intraperitoneal (i.p.) injections of LPS. Thus 7 d after a single i.p. injection of LPS into 1-d-old rats, only a few OX-6 positive cells showing a moderate staining reaction were observed in the corpus callosum. The immunoreactivity diminished 14 d after the injection. However, in rats receiving 2 successive i.p. injections of LPS at 1 and 4 d of age and killed 7 d after the 1st injection, a significant number of intensely stained OX-6 positive amoeboid microglial cells were observed in the corpus callosum. The expression of MHC class II antigens induced by 2 injections of LPS was sustained at least until d 14 when the callosal ramified microglial cells, known to be derived from gradual metamorphic transformation of amoeboid microglia, still exhibited intense immunoreactivity with OX-6. The effect of LPS on the expression of CR3 on amoeboid microglial cells was not obvious after a single injection, but the immunoreactivity with OX-42 was also augmented in rats given 2 i.p. administration of LPS into rats at 1 an 4 d of age. It is concluded from this study that the expression of MHC class I and class II antigens on amoeboid microglial cells in corpus callosum was upregulated and induced respectively after i.v. or i.p. injection of LPS into early postnatal rats. Although relatively fewer in number when compared with OX-18 and OX-42 positive cells, it is suggested that the OX-6 positive cells would have the potentiality to function in antigen presentation in the postnatal rat brain when challenged by the endotoxin.
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PMID:Upregulation and induction of surface antigens with special reference to MHC class II expression in microglia in postnatal rat brain following intravenous or intraperitoneal injections of lipopolysaccharide. 801 20

Human adenoviruses (Ad) contain a complex transcription region (E3) which codes for proteins that interact with several arms of the immune system. However, E3 genes are not essential for replication in tissue culture. An E3-encoded 19,000-molecular-weight (19K) glycoprotein (gp19K) binds to the class I major histocompatibility complex (MHC) in the endoplasmic reticulum and prevents MHC transport to the cell surface. Three other E3 proteins are involved in the inhibition of apoptosis by tumor necrosis factor alpha. The entire E3 genomic DNA was utilized to produce transgenic mice to study the effect of the E3 proteins on pathogenesis of various infectious agents and to investigate the in vivo synthesis and processing of the multiple E3 mRNAs and proteins. There was basal expression of the E3 promoter in the thymus, kidneys, uterus, and testes and at all levels of the gastrointestinal tract. In addition, the E3 promoter of the transgene could be activated in some other organs, including the liver, by infection of these animals with an E3-deficient Ad (Ad7001) which contains a functional E1A region. Transactivation in vivo could also be demonstrated by infusion of bacterial lipopolysaccharide. There appeared to be differential ratios of expression between several of the E3 mRNAs in transgenic lung fibroblasts and primary kidney cells cultured from the transgenic animals. This observation suggested that there was differential mRNA splicing that was organ specific. These transgenic animals should provide a useful model for studying the effects of the E3 proteins on the immune system and on diseases affected either by control of MHC or by selected functions of tumor necrosis factor that are inhibitable by Ad E3 proteins.
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PMID:Characterization of transgenic mice containing adenovirus early region 3 genomic DNA. 805 67

We have investigated the correlation between different tumor necrosis factor (TNF) and class II major histocompatibility complex alleles in the lipopolysaccharide- or phytohemagglutinin-induced secretion of TNF-alpha and TNF-beta by human monocytes and peripheral blood mononuclear cells in 87 unrelated Danish male individuals. Significant differences in TNF-alpha secretory capacity between TNF NcoI restriction fragment length polymorphisms, TNFa and TNFc microsatellite alleles and DR alleles were identified. No correlation with TNF-beta secretory capacity was found for any of the markers studied. TNF genotyping allowed us to define four extended HLA haplotypes which correlate with TNF-alpha secretory capacity. Two of these are DR4 positive: DQw8, DR4, TNFB*1, TNFa6, B44, A2 and DQw8, DR4, TNFB*2, TNFa2, B15, A2. Individuals carrying the TNFB*2, TNFa2 haplotype had a higher TNF-alpha secretory capacity than those carrying the TNFB*1, TNFa6 haplotype. In a group of DR3/DR4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM), the frequency of the TNFa2 allele was higher than in HLA-DR matched controls, whereas the TNFa6 allele was more frequent in control individuals. In the DR3/DR4 heterozygous diabetic group 12/26 had the alleles combination DQw8, DR4 (Dw4), C4A3, TNFB*2, TNFa2, B15, whereas only 1/18 controls had this haplotype. This diabetogenic haplotype is identical to the DR4 haplotype which correlates with a higher TNF-alpha response. These observations suggest a direct role for the TNF locus in the pathogenesis of IDDM.
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PMID:Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. 809 42

In a previous report, we showed that the injection of parental CD4+ T cells into major histocompatibility complex (MHC) class II disparate F1 hybrid mice induces autoimmune-like graft versus-host reaction (GVHR) resembling systemic lupus erythematosus (SLE) and the hepatic lesion of primary biliary cirrhosis (PBC). In the present study, we examined whether or not simultaneous or subsequent injection of CD8+ T cells changes the GVHR form. When parental CD8+ T cells together with CD4+ T cells were injected into MHC class I plus class II-disparate F1 mice, autoimmune phenomena did not develop and alternatively a profound immunosuppressive state was induced. Furthermore, ongoing autoimmune-like GVHR induced by CD4+ T cells was also suppressed by later injection of CD8+ T cells. In these mice, an increase of donor type CD8+ T cells and a marked decrease of host B and T cells in the spleen were observed. The spleen cells from these mice strongly inhibited the mitogenic response of normal spleen cells against lipopolysaccharide (LPS). In vitro studies demonstrated that this immunosuppression was not induced by CD8+ T cells themselves but by macrophages which produced suppressive factor(s) by LPS stimulation. These findings were discussed with reference to suppressive mechanisms of GVHR.
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PMID:Immunosuppressive activity of macrophages in mice undergoing graft-versus-host reaction due to major histocompatibility complex class I plus II difference. 809 68

A human monocyte-derived cell line (THP-1) was used as a model to investigate the role of metallothionein (MT) in the cellular physiology of resting and activated monocytes. MT protein levels were reduced in THP-1 cells by transient transfections with an antisense MT expression vector. Antisense mouse MT-1 RNA was constitutively expressed under the control of the H-2Kb (mouse major histocompatibility complex I) promoter and could be further induced by lipopolysaccharide (LPS) treatment. THP-1 cells expressing antisense MT RNA (aMT-THP-1) had a 30% reduction in MT protein levels. In the absence of LPS treatment, aMT-THP-1 cells demonstrated increased production of H2O2 concurrent with enhanced adherence and invasiveness compared to cells transfected with the control vector (cv-THP-1). Treatment of aMT-THP-1 cells with LPS depressed these activation-associated responses and further reduced the level of MT protein. cv-THP-1 cells activated by LPS produced high levels of H2O2 and adhered to and invaded a reconstituted basement membrane. In addition to increasing cadmium sensitivity, diminished MT levels affected broad-ranging processes associated with resting and activated monocyte function. Thus, metallothionein plays an important physiological role in cells in addition to its role in detoxification of heavy metals.
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PMID:Antisense down-regulation of metallothionein in a human monocytic cell line alters adherence, invasion, and the respiratory burst. 812 89

Tumor growth induces phenotypic and functional changes among splenic T cells and macrophages (M phi) that contribute to the immunosuppression observed in tumor-bearing hosts (TBH). These changes partly arise through alterations in immune cell production of and responsiveness to cytokines. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important T cell- and M phi-derived cytokine that is produced during normal host immunogenic challenge, but it's involvement during cancer is poorly defined. In contrast, interleukin-10 (IL-10) is an inhibitory cytokine that is produced by immune cells as a deactivation factor. IL-10 can disrupt GM-CSF synthesis and may be associated with tumor-induced changes in cytokine synthesis. We determined if tumor growth alters T-cell and M phi synthesis of and responsiveness to GM-CSF, and if these alterations occur because tumor growth heightens immune cell sensitivity to IL-10. Tumor growth significantly decreased T-cell synthesis of GM-CSF during activation by concanavalin A, and TBH T cells were more susceptible to GM-CSF synthesis inhibition by IL-10 than their normal host (NH) counterparts. This suppression was observed using both unseparated splenic lymphocyte preparations and purified CD4+ and CD8+ T cells. Similarly, TBH M phi (both splenic and peritoneal) produced less GM-CSF than NH M phi during activation by lipopolysaccharide. Tumor growth also altered major histocompatibility complex (MHC) class II- M phi GM-CSF synthesis. TBH M phi were more susceptible to GM-CSF synthesis inhibition by IL-10 than their NH counterparts. Although TBH T cells demonstrate less proliferation than NH T cells during activation, tumor growth did not compromise T-cell responsiveness to GM-CSF. However, tumor growth did increase TBH T-cell susceptibility to inhibition of proliferation by IL-10. Tumor growth suppressed M phi responsiveness to GM-CSF, and IL-10 further decreased M phi responsiveness to GM-CSF. Collectively, these results suggest that T cell and M phi production of and responsiveness to GM-CSF is disrupted during tumor growth, and that TBH T cells and M phi are more susceptible to the suppressor activity of IL-10 than their NH counterparts.
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PMID:Tumor growth alters T cell and macrophage production of and responsiveness to granulocyte-macrophage colony-stimulating factor: partial dysregulation through interleukin-10. 813 Dec 7

The ability of bacteria and bacterial products to modulate the expression of Fc gamma receptors and major histocompatibility complex (MHC) class II molecules in resting rat bone marrow-derived mononuclear phagocytes (BMM phi) was determined by means of flow cytometry (FCM). Binding of IgG via Fc gamma receptors was considerably enhanced by most microbial agents; bacterial lipopolysaccharide, lipoteichoic acid and some intact bacteria proved to be as active as interferon-gamma (IFN-gamma) and augmented binding of IgG via high- and low-affinity Fc gamma receptors. In contrast, expression of MHC class II molecules by BMM phi was only slightly affected by the microbial agents. Additional findings attest that resting unprimed rat BMM phi are able to respond directly to Gram-negative and Gram-positive bacteria and to some of their products with the expression of marked secretory [in particular tumour necrosis factor-alpha (TNF-alpha) and nitrite] and cellular activities (TNF-alpha-independent tumoricidal activity). This extensive, direct type of macrophage activation may substantially amplify the capability of these cells to cope with these infectious agents in first-line, non-specific host defence.
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PMID:Macrophage response to bacteria and bacterial products: modulation of Fc gamma receptors and secretory and cellular activities. 813 14

The pathogenicity of interphotoreceptor retinoid-binding protein (IRBP) in the mouse and H-2 restriction of IRBP-induced experimental autoimmune uveoretinitis (EAU) was tested by repeated immunization using Klebsiella pneumoniae 03 lipopolysaccharide (K03-LPS) as an adjuvant. It was shown that IRBP had a greater capacity to induce EAU than S-antigen. Based on the incidence of EAU induction using B10 congenic mice and other strains, the susceptibility to EAU was, at least in part, controlled by the I-Ak haplotype of the H-2 subregion. The results also indicated that non-major histocompatibility complex (MHC) genes play some role in disease susceptibility.
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PMID:Murine experimental autoimmune uveoretinitis induced by interphotoreceptor retinoid-binding protein and Klebsiella pneumoniae 03 lipopolysaccharide (K03-LPS): a relation between H-2 haplotype and EAU induction. 815 76

Macrophages have been shown to undergo a sequential process to full activation in response to priming and triggering signals such as gamma interferon (IFN gamma) and bacterial lipopolysaccharide (LPS). These cells also may be driven directly to full activation by exposure to relatively high concentrations of LPS. Each of the stages to activation is associated with differential protein expression suggesting that newly synthesized proteins are associated with the functional activities attributable to that activation state. These observations indicate that protein profiles may serve as a barometer of the macrophage activation state. Delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, was shown to inhibit inducible protein expression in response to the priming agents Concanavalin A (Con A) supernatant and IFN gamma. THC also suppressed protein expression in response to LPS. P388D1 and RAW264.7 macrophage-like cells, treated with Con A supernatant or IFN gamma, exhibited restructuring of protein profiles based on iso-Dalt two-dimensional gel electrophoresis. Protein profile restructuring, distinctive from that elicited in response to priming agents, was seen for macrophages treated with LPS. Treatment of macrophages with Con A supernatant, IFN gamma, or LPS in concert with THC (10(-7) M to 10(-5) M), resulted in the generation of protein profiles whose patterns reverted approximately to those of unprimed or unactivated macrophages. THC was shown to alter the expression of select proteins whose induction is associated with macrophage priming or activation. The expression of P388D1 macrophage class II Ia molecules of the major histocompatibility complex (MHC), in response to Con A supernatant and IFN gamma, was inhibited. THC also altered the expression of tumor necrosis factor alpha (TNF alpha) elicited by RAW264.7 cells in response to LPS. These results suggest that THC alters macrophage functional activities, at least in part, by suppressing their capacity to express effector molecules elicited in response to priming and activating signals.
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PMID:Inhibition of macrophage inducible protein expression by delta-9-tetrahydrocannabinol. 819 97

Dendritic cells (DC) can provide all the known costimulatory signals required for activation of unprimed T cells and are the most efficient and perhaps the critical antigen presenting cells in the induction of primary T cell-mediated immune responses. It is now shown that mouse cell lines with many of the features of DC can be generated using the MIB phi 2-N11 retroviral vector transducing a novel envAKR-mycMH2 fusion gene. The immortalized dendritic cell line (CB1) displays most of the morphologic, immunophenotypic, and functional attributes of DC, including constitutive expression of major histocompatibility complex (MHC) class II molecules, costimulatory molecules B7/BB1, heat stable antigen, intracellular adhesion molecule 1, and efficient antigen-presenting ability. Granulocyte/macrophage colony-stimulating factor (GM-CSF) proved to be effective in increasing MHC class II molecule expression and in enhancing presentation of native protein antigens. In comparison with macrophages, CB1 dendritic cells did not exhibit phagocytic and chemotactic activity in response to various stimuli and lipopolysaccharide activation was ineffective in inducing tumor necrosis factor alpha or interleukin 1 beta production. CB1 cells, pulsed with haptens in vitro and injected into naive mice were able to induce delayed-type hypersensitivity responses, further increased with pretreatment with GM-CSF, indicating that these cells may represent an immature, rather than a mature DC. The ability of CB1 to prime T cells in vivo could provide a tool to design novel immunization strategies.
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PMID:Immortalized dendritic cell line fully competent in antigen presentation initiates primary T cell responses in vivo. 824 71


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