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)

Intercellular adhesion in lymphocytes is mediated in part by the interaction of the integrin lymphocyte function-associated antigen-1 (LFA-1) with intercellular adhesion molecule-1 (ICAM-1). The B lymphoblastoid line JY expresses both LFA-1 and ICAM-1, and intercellular adhesion is enhanced by treatment with the phorbol ester phorbol 12-myristate 13-acetate (PMA), which also induced capping of LFA-1, ICAM-1, and human leukocyte antigen. Capping of LFA-1 is likely to result from protein kinase C (PKC) activation because receptor-mediated stimulation of PKC also led to capping. Additionally, adhesion mediated by PMA or lipopolysaccharide was blocked by either of two PKC inhibitors, calphostin C and staurosporine. PMA induced the apparent condensation of cytoskeletal elements that colocalized with the membrane protein cap. Cytoskeletal condensation and capping occurred in the absence of intercellular adhesion. Alteration in the distribution of cytoskeletal components and membrane redistribution of LFA-1 were inhibited by cytochalasin D, which also abolished intercellular adhesion. Taken together, these data suggest that intercellular adhesion is the result of PKC-mediated membrane redistribution of LFA-1 and ICAM-1, which is in turn associated with modification of the actin-based cytoskeleton.
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PMID:Lymphocyte adhesion can be regulated by cytoskeleton-associated, PMA-induced capping of surface receptors. 156 18

Previously, we prepared extracellular products, fractions F-1 and F-2 of Streptococcus mitis 108, an isolate from the tooth surface of an infant, and showed that F-1 exhibited inflammatory cytokine-inducing activities. In the present study, we present evidence that fraction F-2 induced human T-cell proliferation in the presence of irradiated human peripheral blood mononuclear cells and selectively activated T cells bearing V beta 2 and V beta 5.1 in the T-cell receptor. F-1, on the other hand, stimulated human gingival fibroblasts to support the T-cell proliferation in the same way as human gamma interferon or Prevotella intermedia lipopolysaccharide (LPS). Fraction F-1 also primed gingival fibroblasts to support the production of interleukin-2 and gamma interferon by the T cells upon stimulation with F-2. Human gingival fibroblasts stimulated with fraction F-1, like those stimulated by P. intermedia LPS and human gamma interferon, exhibited human leukocyte antigen (HLA)-DR mRNA expression and cell surface HLA-DR molecules as detected by enzyme-linked immunosorbent assay. An anti-HLA-DR monoclonal antibody inhibited T-cell proliferation in response to F-2, probably through inactivating the accessory function of HLA-DR-bearing fibroblasts. T cells activated with F-2 in the presence of irradiated peripheral blood mononuclear cells exhibited definite cytotoxic effects against fibroblasts and squamous carcinoma cells originating from human oral tissues. These findings are strongly suggestive of an association of extracellular products of viridans streptococci with pathogenesis of oral mucosal diseases, particularly those disorders in gingiva which are accompanied by heavy infiltration of T cells.
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PMID:Immunopathological activities of extracellular products of Streptococcus mitis, particularly a superantigenic fraction. 786 48

Tumor necrosis factor alpha (TNF alpha) is a central mediator of the immunological response and the location of the gene within the major histocompatibility complex (MHC) has prompted much speculation about the role of TNF alpha alleles in inflammatory and MHC-associated autoimmune diseases. A G to A transition polymorphism at position -308 of the TNF alpha promoter/enhancer region has been described. The uncommon -308A allele was shown to be strongly associated with human leukocyte antigen (HLA)-DR3, known to be related to a TNF alpha "high producer" phenotype. In support for a clinical relevance, the -308A allele is implicated in susceptibility for cerebral malaria. In this study, we determined the junctional consequences of the TNF -308 polymorphism. Therefore, we analyzed both allelic forms (TNF alpha(-308G) and TNF alpha(-3O8A)) of the TNF alpha enhancer/promoter region (-598/+108) in a transient transfection system, using chloramphenicol acetyltransferase (CAT) as reporter gene. The T cell line Jurkat and the B cell line Raji served as hosts in these experiments. The results showed no differences in the level of inducible reporter gene expression between the TNF(-3O8G)/CAT and the TNF(-308A)/CAT constructs. These data were confirmed by allele specific TNF alpha transcript quantification (ASTQ) analysis, which demonstrated that both TNF alleles contribute equally to the total amount of mRNA in peripheral blood mononuclear cells (PBMCs) stimulated with phorbol 12-myristate 13-acetate (PMA)/anti-CD3. In analogy, no difference between the level of transcription of the -308A and -308G alleles was observed in lipopolysaccharide (LPS)-stimulated peripheral blood monocytes. This study indicates that the TNF alpha -308 G to A transition is not responsible for differential TNF alpha production induced by standard in vitro stimuli.
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PMID:Relevance of the tumor necrosis factor alpha (TNF alpha) -308 promoter polymorphism in TNF alpha gene regulation. 883 66

Bacterial cell wall products such as lipopolysaccharide (LPS) and muramyl dipeptide (MDP) have the capacity to enhance immune responses to antigens. The expression of surface class II major histocompatibility antigens and the costimulatory receptors CD18 and CD54/ICAM-1 (intercellular adhesion molecule) was used to evaluate the comparative influence of these immunostimulators. On monocytes, both LPS and MDP increased the expression of human leukocyte antigen (HLA)-DR (maximal at 6 hr), CD18 (maximal at 1-3 hr), and ICAM-1 (maximal at 18-24 hr for LPS and 12 hr for MDP) without increasing the production of superoxide. MDP-induced ICAM-1 expression on monocytes returned to baseline values after 12 hr. On lymphocytes, only LPS increased ICAM-1 (after 18 hr) without affecting CD18, and a differential analysis demonstrated a generalized ICAM-1 upregulation in lymphocyte subsets after 18 hr: the most pronounced effect was measured in natural killer cells, followed by CD8(+) T cells, B cells, and CD4(+) T cells. MDP did not alter ICAM-1 or CD18 expression on lymphocytes. These similar but smaller effects of MDP may, in part, explain the lesser toxicity of MDP when compared to LPS.
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PMID:Bacterial cell wall products increase monocyte HLA-DR and ICAM-1 without affecting lymphocyte CD18 expression. 907 85

A patient presented with the unique clinical picture of diffuse cutaneous and mucosal leishmaniasis caused by Leishmania tropica. Elevated serum levels of several cytokines including interleukin (IL) 2, interferon gamma (IFN-gamma), and tumor necrosis factor alpha were found. All cytokine levels returned to normal during therapy. No IL-10 or IL-4 levels were detectable. In whole blood cultures, induction of IFN-gamma by lipopolysaccharide (LPS) was completely negative, even after therapy. Concanavalin A (Con A)-induced release of IFN-gamma, like Con A-induced release of the other cytokines, was only initially impaired but returned to normal during therapy. Induction of the other cytokines by LPS was never impaired. The low expression of human leukocyte antigen DR on monocytes increased during IFN-gamma therapy but dropped when IFN-gamma treatment was ceased. We conclude that in this patient one or more of the routes of IFN-gamma production was impaired, thus resulting in insufficient IFN-gamma production in the infected lesions (although IFN-gamma was systemically present).
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PMID:Impaired production of cytokines in a case of human leishmaniasis. 943 72

The aim of this study was to assess the biological characteristics of four new malignant mesothelioma (MM) cell lines. Since simian virus (SV)40 sequences have been recently detected in MM, SV40 large T antigen (Tag) expression was also analysed. MM cell lines were characterized by morphological, ultrastructural and cytogenetic analysis. Expression of Tag and of relevant MM markers was studied by immunocytochemistry, surface antigens by indirect immunofluorescence and immunomodulating cytokines by enzyme-linked immunosorbent assay (ELISA). The four MM cell lines, established from pleural effusions, showed a slow proliferation rate and pleomorphic changes during culture. Cell lines expressed vimentin, cytokeratins 8 and 18, and the mesothelial antigen recognized by HBME-1 monoclonal antibody, but not carcinoembryonic antigen. Surface human leukocyte antigen (HLA)-class I and intercellular adhesion molecule (ICAM)-1 molecules were present on all the cell lines. While HLA class II and CD86 were constitutively undetectable, HLA-class II was present after interferon (IFN)-gamma stimulation. All cell lines displayed abnormal karyotypes with chromosome 6 abnormalities. Transforming growth factor (TGF)-beta2 and interleukin (IL)-6 were constitutively secreted, while tumour necrosis factor (TNF)-alpha was secreted only in response to lipopolysaccharide. Intranuclear Tag was expressed in two cell lines. The persistence of large T antigen with human leukocyte antigen class I and intercellular adhesion molecule-1 positivity may point to large T antigen as a target for cytotoxic T-lymphocyte-based immunotherapy in some malignant mesothelioma patients.
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PMID:Establishment of four new mesothelioma cell lines: characterization by ultrastructural and immunophenotypic analysis. 1023 21

Tachykinins such as substance P (SP) may be involved in the pathogenesis of inflammatory airway diseases such as asthma. This study investigated the presence of SP and its receptor in the differentiated macrophage-like U-937 cell line and in macrophages from sputum induced in healthy subjects (n=8). In situ hybridization with digoxigenin-labelled sense and antisense complementary ribonucleic acid (cRNA) probes was used to determine the expression of SP and its receptor (neurokinin (NK)1 receptor). SP-immunoreactive material was detected using a rabbit anti-SP antiserum and the alkaline phosphatase anti-alkaline phosphatase technique. Beta-preprotachykinin (PPT)-I messenger ribonucleic acid (mRNA) encoding SP, was detected using in situ hybridization in differentiated U-937 cells as well as in CD45+ human leukocyte antigen (HLA) DR+ sputum macrophages. The expression of the beta-PPT-I mRNA was increased in lipopolysaccharide (LPS)-stimulated U-937 cells. SP-immunoreactive material was found in differentiated U-937 cells and in CD68+ sputum macrophages. NK1 receptor mRNA was detected in differentiated U-937 cells and sputum macrophages. Incubation of U-937 cells with SP considerably increased the expression of NK1 receptor mRNA. This study demonstrates that human monocytes/macrophages express substance P and that this expression is upregulated by lipopolysacharide. Human monocytes/macrophages also express neurokinin1 receptor messenger ribonucleic acid, suggesting an autocrine effect of substance P on these cells.
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PMID:Presence of substance P and neurokinin 1 receptors in human sputum macrophages and U-937 cells. 1057 19

Very little is known about alveolar macrophage (AM) immunological function in early childhood. Using nonbronchoscopic bronchoalveolar lavage (BAL), this study sought to compare the proportion, number, and function of AM between very young and older children. BAL fluid (BALF) leukocyte parameters were determined in 63 children, and data divided into 3 age groups: group 1 (<2 yrs), group 2 (> or =2-< or =5 yrs) and group 3 (> or =6-< or =17 years). In a further subgroup of children, AM function and immune receptor expression were assessed, and data categorized into two age groups: <2 yrs and > or =2 yrs of age. Compared to groups 2 and 3, the AM percentage in the BAL in group 1 was significantly increased (median: 98% versus 92% and 91%), as was the albumin-adjusted AM concentration. AM from children <2 yrs expressed less human leukocyte antigen (HLA)-DR (versus > or =2 yrs of age), were less effective in reducing nitro blue tetrazolium, and released less interleukin (IL)-1 and tumour necrosis factor on lipopolysaccharide stimulation. There was no difference in release of IL-6, expression of intercellular adhesion molecule-1 (CD54), and AM stimulation of allogeneic T-cells, between children <2 yrs and > or =2 yrs of age. It was concluded that the capacity of alveolar macrophage to stimulate T-cells is not enhanced in early childhood, and that immaturity of alveolar macrophage function may contribute to an increased susceptibility to respiratory infections in this age group.
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PMID:Alveolar macrophage immaturity in infants and young children. 1059 13

Endotoxin (lipopolysaccharide (LPS), 100 ng/ml) and muramyl dipeptide (MDP 100 ng/ml), two immunomodulatory bacterial cell wall products, were incubated with human whole blood, and the expression of receptors involved in antigen presentation, costimulation, and cell activation was investigated by use of flow cytometry. On monocytes, LPS and MDP increased surface expression of human leukocyte antigen-DR (HLA-DR), CD18, CD54 (intercellular adhesion molecule-1, ICAM-1), and CD86 (B7-2). On lymphocytes, LPS but not MDP increased HLA-DR expression after 18 h. The expression of CD28, CD49d/CD29, and CD106 (vascular cell adhesion molecule-1, VCAM-1) remained unchanged on both monocytes and lymphocytes. The early increase (1-6 h) of CD18 and ICAM-1 expression led us to hypothesize that CD18-dependent costimulatory signals were involved in the later (6 h) increase of monocyte HLA-DR expression. However, blocking studies using monoclonal antibodies against CD18 (IB4, 15 microg/ml) demonstrated that the LPS- and MDP-induced increase of HLA-DR and ICAM-1 expression on monocytes was not mediated through CD18. LPS induced the expression of the early activation marker CD69 by a CD14-dependent but CD18-independent mechanism, whereas MDP did not induce CD69 expression. Analysis of leukocyte subsets demonstrated that CD4(+) T-cells, CD8(+) T-cell, CD19(+) B-cells, CD56(+) natural killer (NK)-cells, and CD14(+) monocytes increased the expression of CD69 after stimulation with LPS. Collectively, these data demonstrate a stronger immunomodulatory effect of LPS compared with MDP which may, in part, explain the established difference of toxicity between these two bacterial cell wall products.
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PMID:Endotoxin and muramyl dipeptide modulate surface receptor expression on human mononuclear cells. 1093 9

Multiple sclerosis (MS) typically presents with a relapsing-remitting onset. This can be distinguished from primary progressive MS. Typical MS is characterized by a profound inflammatory reaction in which anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor (TNF) may play a pivotal role. We tested the hypothesis that patients with MS have a distinct innate cytokine production that contributes to the susceptibility for and outcome of MS. The innate cytokine production of patients was estimated as the average production of cytokines in lipopolysaccharide -stimulated whole-blood cultures of 2 to 5 first-degree healthy family members. A total of 126 family members of 50 patients with typical MS, 61 family members of 25 patients with primary progressive MS, and 129 control subjects of 54 families were enrolled in this study. We found that members of families with low IL-10 and high TNF production had a fourfold increased risk of developing typical MS compared with members of families with high IL-10 and low TNF production. Patients with MS were eightfold more likely to develop typical MS than primary progressive MS when they belonged to families with low IL-10 and high TNF production. The presence of human leukocyte antigen-DR2 was associated with MS but not with TNF production. This study shows that typical MS is associated with an innate pro-inflammatory cytokine profile in contrast to primary progressive MS.
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PMID:Innate production of interleukin-10 and tumor necrosis factor affects the risk of multiple sclerosis. 1102 48


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