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)

Murine Ly1+ pre-B cell lines, including 70Z/3 and three pre-B cell lines derived from long-term bone marrow cultures, exhibited selective adherence to bone marrow stromal cells. In contrast, splenic B cells, the A20 B-cell lymphoma, and four Ly1- B cell lines derived from long-term bone marrow cultures failed to adhere substiantially to bone marrow cultures failed to adhere substiantially to bone marrow stroma. Ly1+ pre-B cell lines were induced to express kappa light chains by exposure to either lipopolysaccharide (LPS), recombinant interleukin-1 (IL-1), or stromal cells. However, induction of kappa light chains failed to prevent pre-B cell adherence to stromal cells. Supernatants derived from primary bone marrow stromal cells decreased Ly1 expression on the Ly1+ pre-B cell lines. These experiments suggest that (1) expression of immunoglobulin light chains by developing Ly1+ pre-B cells is mediated by bone marrow stromal cells; (2) loss of specific adherence to stroma is progressive and occurs post-light chain induction; and (3) soluble products of stromal cells may downregulate expression of surface Ly1 on otherwise Ly1+ pre-B cells. The importance of these observations to the development of both the Ly1- and Ly1+ B cell lineages in the mouse is discussed.
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PMID:Bone marrow stromal cells modulate both kappa light chain and Ly1 antigen expression on Ly1+ pre-B cell lines in vitro. 211 35

Two nuclear phosphoproteins, pp35 and pp32, were purified from A20 cells, a murine B-lymphoblastoid cell line. Initially detected by cross-reactivity with antibodies to human erythrocyte protein 4.1, the 35- and 32-kDa proteins were purified by sequential fractionation of non-ionic detergent cell lysates on DEAE-cellulose, high performance liquid chromatography (HPLC)-anion-exchange chromatography, and HPLC hydroxylapatite chromatography. By two-dimensional peptide mapping, pp35 and pp32 are related but do not appear to represent sequential proteolytic products. Both pp35 and pp32 appear to be associated with cell proliferation. Antibodies specific for pp35 and pp32 show prominent intranuclear staining in A20 cells but only focal staining in normal murine lymphoid tissues. Quantitative immunoblotting showed that both pp35 and pp32 are, respectively, expressed at 5.9 x 10(4) and 7.0 x 10(4) copies/cell in small, dense resting B lymphocytes, increasing approximately 12- and 7-fold after polyclonal stimulation with lipopolysaccharide. When normalized to total cell protein, this represents specific inductions of approximately 4- and 2-fold. Expression of both pp35 and pp32 is constitutively high in populations of neoplastic B cell lines; moreover, both are expressed in the nuclei of intestinal crypt epithelial cells but not in other epithelial compartments in the same sections, suggesting that forms of pp35 and pp32 may be expressed in additional tissues and associated with proliferation.
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PMID:Identification and preliminary characterization of two related proliferation-associated nuclear phosphoproteins. 237

In this study we have evaluated some of the potential mechanisms that may be responsible for the inefficiency with which resting B cells function as antigen-presenting cells (APC) and the mechanism by which that function is enhanced following treatment of B cells with neuraminidase. One mechanism that has been previously suggested is that glycosylation differences in Ia associated with different APC accounts for the different functional capacities of resting and activated B cells. It has been postulated that removal of sialic acid from resting B cell Ia results in a correction of its antigen-presenting defect. To study this possibility, we have used purified I-Ad from different B cell sources in a planar membrane system to present an immunogenic peptide of chicken ovalbumin (Ova) to an I-Ad-restricted Ova-specific T cell hybridoma. It was found that I-Ad isolated from resting B cells, B cell stimulatory factor 1 (BSF-1) or lipopolysaccharide and dextran sulfate-stimulated B cells, or A20 B lymphoma cells were all equivalent in their antigen-presenting capacity. Furthermore, removal of sialic acid from Ia did not enhance its capacity to serve as a restriction element. The mechanism by which neuraminidase treatment enhances B cell APC function was further investigated by studying the effect of sialic acid removal on a primary mixed leukocyte reaction (MLR). When allogeneic fixed B cells were used as stimulator cells it was found that neither resting nor BSF-1-stimulated B cells could induce a MLR. Following neuraminidase treatment, BSF-1-treated B cells, but not resting B cells, were capable of stimulating a MLR. However, a MLR was also stimulated by allogeneic BSF-1-treated B cells when the responder T cells, rather than the stimulator cells, were treated with neuraminidase. An enhancing effect similar to that obtained by neuraminidase treatment could be obtained by the addition of 2% polyethylene glycol to the MLR culture. These data suggest that the inability of BSF-1-stimulated cells to function efficiently as accessory cells in stimulating a primary MLR is due to their relative inability to interact physically with T cells, a deficiency that is overcome by neuraminidase treatment of either T or B cell populations or by the addition of polyethylene glycol to the culture. Although the reason for the failure of these same treatments to restore the accessory cell function of resting B cells is not known, some possible mechanisms are discussed.
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PMID:Studies on the capacity of intact cells and purified Ia from different B cell sources to function in antigen presentation to T cells. 296 12

Increases in intracellular free calcium concentration ((Ca2+)i) were observed in response to anti-immunoglobulin (Ig) antibodies in each of six B cell tumors or B cell hybridomas bearing mu or delta chains on their cell surface. The BAL17 cell line, bearing mu and delta chains on its surface, behaved similarly to mature B cells in the following respects. Anti-IgM and anti-IgD antibodies caused increases in (Ca2+)i and inositol phospholipid metabolism; the initial increases in (Ca2+)i were derived partly from an intracellular Ca2+ pool; lipopolysaccharide, phorbol myristate acetate (PMA), B cell stimulatory factor-1, and antibodies to class I and class II major histocompatibility molecules and to the Fc gamma receptor failed to cause increases in (Ca2+)i or in inositol phospholipid metabolism; and increases in (Ca2+)i and inositol phospholipid metabolism in response to anti-Ig were inhibited by pretreatment with PMA. Furthermore A20, an IgG2a bearing lymphoma, showed increases in (Ca2+)i in response to anti-IgG2a, and a lymphoma cell line (6G8-2E10) expressing membrane IgG2b as a result of DNA-mediated transfer of the gamma 2b H chain gene, showed increases in (Ca2+)i in response to anti-IgG2b. These results indicate that Ig-bearing lymphomas display early events in B cell activation after receptor cross-linkage and can be used for detailed studies of the activation process.
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PMID:Membrane IgM, IgD, and IgG act as signal transmission molecules in a series of B lymphomas. 302 Jan 22

B cells have been shown to present antigen to T cells very efficiently through their capacity to capture antigens by their membrane immunoglobulin. This direct cognate interaction of T and B cells results in the proliferation and differentiation of B cells. This concept has been established using soluble proteins. However, most of the antigens to which the immune system is exposed are included in complex particulate structures such as bacteria or parasites. The capacity of B cells to present these large and complex antigens is still unclear. To address this question we have studied the presentation by trinitrophenyl (TNP)-specific B cells of the same antigen TNP-KLH (keyhole limpet haemocyanin), either in a soluble form or covalently linked to poly(acrolein) microspheres, from 0.25 to 1.5 microns in diameter. In the presence of irradiated splenocytes or purified macrophages as a source of antigen-presenting cells (APC), KLH-specific T cells proliferated in response to soluble TNP-KLH or to TNP-KLH coupled to beads. In contrast, TNP-specific memory B cells were totally ineffective in presenting the TNP-KLH beads to KLH-specific T cells whereas they presented very efficiently soluble TNP-KLH. Similar results were obtained with the A20 B lymphoma or with lipopolysaccharide (LPS)-activated TNP-specific B cells. These results therefore indicate that B cells are unable to present large size particulate antigens such as bacteria or parasites.
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PMID:B cells do not present antigen covalently linked to microspheres. 850 43

The A20 gene product is a novel zinc finger protein originally described as a tumor necrosis factor alpha (TNF)-inducible early response gene in human umbilical vein endothelial cells (HUVEC). Its described function is to block TNF-induced apoptosis in fibroblasts and B lymphocytes, but more recently it has also been shown to play a role in lymphoid cell maturation. The mechanism of action of A20 is unknown. The aim of our study was to assess the effect of A20 upon endothelial cell activation. By transfecting bovine aortic endothelial cells (BAEC) with A20 as well as reporter constructs consisting of the promoters of genes known to be up-regulated during endothelial cell activation, i.e. E-selectin, interleukin (IL)-8, tissue factor (TF), and inhibitor of nuclear factor kappaBalpha (IkappaBalpha), we demonstrate that A20 expression inhibits gene up-regulation associated with TNF, lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), and hydrogen peroxide (H2O2)-induced endothelial cell (EC) activation. The mechanism of action of A20 is in part, or totally, due to the blockade of nuclear factor kappaB (NF-kappaB), as shown by its ability to suppress the activity of a NF-kappaB reporter. This effect is specific, as A20 does not block a noninducible, constitutively expressed reporter, Rous sarcoma virus-luciferase (RSV-LUC); nor does it block the c-Tat-inducible, NF-kappaB-independent reporter, human immunodeficiency virus-chloramphenicol acetyltransferase (HIV-CAT). How A20 blocks NF-kappaB is unclear, although we demonstrate that it does not affect p65 (RelA)-mediated gene transactivation. The inhibition of endothelial cell activation by A20 is a novel function for A20.
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PMID:A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. 866 99

Inhibitors of p38 mitogen-activated protein kinase (p38) have been reported to block tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) production in monocytes at the level of mRNA translation. Yet, several studies document that p38 can phosphorylate and activate specific transcription factors. Thus, to understand better the role of p38 during monocyte activation, we sought to determine the extent to which p38 is required for lipopolysaccharide (LPS)-induced gene expression. For this, differential mRNA display was used to identify LPS-induced genes whose expression was blocked by SB202190, a specific inhibitor of p38. A partial screen identified 10 genes in monoyctes induced 4- to 74-fold by LPS. Of these, genes encoding interferon-induced gene 15, neuroleukin, radiation-inducible immediate-early gene-1, A20, IL-1beta, and superoxide dismutase were suppressed >50% by SB202190. LPS-induced gene activation was not blocked by cycloheximide, indicating that synthesis of intermediate proteins was not required. SB202190 blocked gene induction by 50% when present between 41 and 123 nM, consistent with the potency of this compound as a p38 inhibitor. Furthermore, the ability of SB202190 to block gene activation was stimulus-dependent. LPS and interferon-alpha (IFN-alpha) both up-regulated neuroleukin mRNA, but only LPS-induced neuroleukin mRNA was suppressed by SB202190. In contrast, TNF-alpha and LPS both induced IL-8 mRNA, and induction by either TNF-alpha or LPS was blocked by SB202190. These data were consistent with the ability of LPS and TNF-alpha, but not IFN-alpha, to activate p38 in monocytes. The results provide pharmacological evidence that p38 may be a key mediator of inducible gene expression in monocytes, but its role is stimulus and gene specific.
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PMID:SB202190, a selective inhibitor of p38 mitogen-activated protein kinase, is a powerful regulator of LPS-induced mRNAs in monocytes. 973 69

We studied the signal transduction pathways involved in NF-kappaB activation and the induction of the cytoprotective A20 gene by lipopolysaccharide (LPS) in human umbilical vein endothelial cells (HUVEC). LPS induced human A20 mRNA expression with a maximum level 2 h after stimulation. The proteasome inhibitor N-acetyl-leucinyl-leucinyl-norleucinal-H (ALLN) and the tyrosine kinase inhibitor herbimycin A (HMA) blocked A20 mRNA expression and partially inhibited NF-kappaB DNA-binding activity induced by LPS treatment. LPS induced IkappaBalpha degradation at 30-60 min after treatment, but did not induce IkappaBbeta degradation up to 120 min. In contrast, TNF-alpha rapidly induced IkappaBalpha degradation within 5 min and IkappaBbeta degradation within 15 min. Cycloheximide did not prevent LPS-induced IkappaBalpha degradation, indicating that newly synthesized proteins induced by LPS were not involved in LPS-stimulated IkappaBalpha degradation. LPS-induced IkappaBalpha degradation was inhibited by ALLN, confirming that ALLN inhibits NF-kappaB activation by preventing IkappaBalpha degradation. Of note, HMA also inhibited LPS-induced IkappaBalpha degradation. However, tyrosine phosphorylation of IkappaBalpha itself was not elicited by LPS stimulation, suggesting that tyrosine phosphorylation of a protein(s) upstream of IkappaBalpha is required for subsequent degradation. We conclude that in HUVEC, LPS induces NF-kappaB-dependent genes through degradation of IkappaBalpha, not IkappaBbeta, and propose that this degradation is induced in part by HMA-sensitive kinase(s) upstream of IkappaBalpha.
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PMID:Lipopolysaccharide-induced NF-kappaB activation in human endothelial cells involves degradation of IkappaBalpha but not IkappaBbeta. 974 2

The effect of lipopolysaccharide (LPS) on endothelial cells is a key component of the inflammatory response seen in Gram-negative sepsis. LPS does not cause death of cultured human endothelial cells. However, when the expression of new proteins is inhibited by cycloheximide, microvascular endothelial cells in culture undergo apoptosis. This finding suggests that LPS induces apoptotic and antiapoptotic pathways, with the antiapoptotic response being dependent on the synthesis of new proteins. Concurrent activation of apoptotic and antiapoptotic pathways has previously been documented for tumor necrosis factor (TNF). In the case of TNF, the antiapoptotic signal has been attributed to at least two cytoprotective proteins: the Bcl-2 homologue, A1, and the zinc-finger protein, A20. In this study, we demonstrate that both these molecules are induced in microvascular endothelial cells by LPS. Enforced overexpression of either A1 or A20 inhibits LPS and cycloheximide-initiated apoptosis. Induction of A1 and A20 does not require synthesis of intermediary proteins, but is dependent on the presence of soluble CD14. In addition, we show that inhibition of signaling by the transcription factor, NF-kappaB, blocks accumulation of A1 and A20 mRNA. Taken together, our findings suggest that LPS directly induces expression of the cytoprotective proteins, A1 and A20, via a CD14-dependent pathway requiring activation of NF-kappaB.
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PMID:Lipopolysaccharide induces the antiapoptotic molecules, A1 and A20, in microvascular endothelial cells. 976 60

Monoclonal antibodies (MAbs) that inhibit adhesion of Helicobacter pylori to human gastric cancer (MKN45) cells were established to clarify the mechanism of adhesion of H. pylori. Of 53 hybridoma clones screened by the primary inhibition assay for adhesion, MAb A20 of IgM class was selected on the basis of both its reactivity to whole cells of H. pylori by ELISA and its inhibitory effect on adhesion of H. pylori. The adhesion of H. pylori strain TK1029 to MKN45 cells was inhibited by MAb A20, depending on the concentration of the MAb. The MAb recognised the surface antigen, lipopolysaccharide (LPS) of H. pylori, suggesting that LPS is associated with adhesion of H. pylori to human gastric epithelial cells.
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PMID:Establishment and characterisation of a monoclonal antibody to inhibit adhesion of Helicobacter pylori to gastric epithelial cells. 987 69


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