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)

Stimulation with lipopolysaccharide (LPS) initiated monocytes to produce interleukin-2 receptor light chain (p55 IL-2R). After stimulation with LPS for 48 hr, considerable quantities of soluble IL-2R were found in the supernatants of monocytes, exceeding even the amount of soluble IL-2R produced by activated T lymphocytes. Cell-associated p55 IL-2R was also increased during the first 24 hr of stimulation, after which time it remained constant. Fractionation of cells and analysis of cytoplasm, mitochondria, plasma membranes and nuclei for the presence of p55 IL-2R revealed that the main portion of receptor was present in the cytoplasm. This led to the conclusion that in monocytes cell-associated p55 IL-2R is not necessarily attached to membranes but is present in a soluble form in the cytoplasm, presumably freshly produced with the aim of being secreted. Stimulation of monocytes with pure recombinant interferon-gamma did not lead to augmentation of p55 IL-2R, as shown by enzyme-linked immunosorbent assay, binding of antibodies directed against the receptor (anti-Tac, CD25) and analysis of p55 IL-2R gene expression.
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PMID:The monocyte interleukin-2 receptor light chain: production of cell-associated and soluble interleukin-2 receptor by monocytes. 155 92

In view of the central involvement of interleukin-1 (IL-1) in T-cell functions and the negative effects exerted by cyclic adenosine monophosphate (cAMP) on T-cell responses, we wondered whether these inhibitions rely on defects in IL-1 generation. We investigated the effect of a known cAMP elevating agent, cholera toxin (CT), on the generation of IL-1 from peripheral blood adherent cells as well as the role of IL-1 whenever IL-2 synthesis and IL-2 receptor (CD25 antigen) expression are inhibited. While augmenting intracellular cAMP concentration, CT inhibits from 20 to 40% the generation of IL-1 activity from E. coli lipopolysaccharide (LPS)-stimulated adherent cells. Theophylline (TH), a cAMP degradation blocking agent, induces the same decrease in IL-1 activity. The B chain of CT, devoid of cAMP activating potency, is not inhibitory. In systems where CT and TH dramatically inhibit the generation of IL-2 activity (80%), addition of exogenous IL-1 does not restore the ability of T-cells to produce or release IL-2. Moreover, CT- and dibutyryl (db)cAMP-induced inhibition of CD25 antigen expression is not overcome by exogenous IL-1, IL-2, nor by both interleukins. It is concluded that inhibition of IL-1 and IL-2 production are independent and that inhibition of CD25 antigen expression is independent of IL-1 and IL-2 modulation. Cholera toxin and cAMP influences on interleukin synthesis are discussed.
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PMID:Elevation of cyclic adenosine monophosphate levels independently down regulates IL-1, IL-2, and IL-2 receptor (CD25) syntheses. 217 38

Exposure (24 hr) to a single intratracheal administration of gallium arsenide (GaAs; 200 mg/kg) has been shown to suppress antibody production as well as other T cell-mediated immunological functions. GaAs has also been shown to exert toxic effects on events occurring early in the antibody-forming cell response which may include lymphocyte activation and proliferation. Studies were undertaken to determine whether GaAs exposure resulted in the inability of T and B lymphocytes to proliferate in response to an antigenic stimulus. During the first 24 hr after in vitro immunization with sheep red blood cells, GaAs-exposed splenocytes were suppressed 51% in their ability to proliferate compared to the vehicle (0.05% Tween 80 in saline; VH) control. There was no significant difference in absolute numbers of cluster designation (CD)8+ cells between VH- and GaAs-exposed cultures. There was, however, a 50% decrease in CD4+ cells evaluated 24 hr after immunization with sheep red blood cells which persisted for the 5-day culture period. T and B cells were isolated and analyzed for proliferative capacity in response to various mitogenic stimuli. Isolated B cells exhibited no difference between VH- and GaAs-exposed cells in proliferative capacity to either lipopolysaccharide or anti-immunoglobulin plus interleukin-4. However, isolated T cells exposed to GaAs were significantly suppressed in their ability to proliferate to concanavalin A, phytohemagglutinin and anti-CD3 epsilon plus interleukin-2 when compared to VH. In addition, expression of CD25, leukocyte function antigen-1 and intercellular adhesion molecule-1 in GaAs-exposed mice were significantly below VH (36, 18 and 18%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gallium arsenide selectively inhibits T cell proliferation and alters expression of CD25 (IL-2R/p55). 809 42

Alveolar macrophages (AMs) from patients with interstitial lung diseases, such as sarcoidosis and idiopathic pulmonary fibrosis, suppress the phytohaemagglutinin (PHA) stimulation of autologous peripheral lymphocytes. The aim of this study was to determine whether the suppressive effect of alveolar macrophages of patients with interstitial lung disease is due, not only to the secretion of soluble factors prostaglandin E2 (PGE2), interleukin-1 (IL-1) but is also correlated to a direct effect of AMs on the expression of IL-2 receptors (IL-2R: CD25) and on the induction of IL-2 activity. We studied 26 subjects, 8 with sarcoidosis, 7 with idiopathic pulmonary fibrosis, and 11 controls. Alveolar macrophages of sarcoid and idiopathic pulmonary fibrosis patients suppressed proliferation of autologous peripheral lymphocytes by 68 +/- 14% and 53 +/- 4.5%, respectively, compared to enhancement of 19 +/- 11% in three controls and suppression of 25 +/- 11% in the other six controls; the difference between subjects with interstitial lung disease and controls was significant. As already reported, the alveolar macrophages of sarcoid patients secreted large amounts of IL-1 (184 +/- 59 U.ml-1) whereas the alveolar macrophages from idiopathic pulmonary fibrosis patients secreted large amounts of PGE2 (3.6 +/- 2 ng.ml-1 x 10(-5) cells) compared with 23 +/- 19 U.ml-1 IL-1 and 0.34 +/- 0.15 ng.ml-1 x 10(-5) cells respectively, of controls. Suppression by supernatants recovered from lipopolysaccharide (LPS) stimulated alveolar macrophages can only partially explain the high suppressive effect of alveolar macrophages of interstitial lung diseases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppressive mechanisms of alveolar macrophages in interstitial lung diseases: role of soluble factors and cell-to-cell contact. 837 Apr 44

The U937 cell, a human monoblast cell line, has been used as a model to study the function of human monocytes. We investigated the effects of interferon-gamma (IFN-gamma) on superoxide anion (O2-) production, cell surface antigens, and cytokine production of U937 cells. IFN-gamma treatment enhanced O2- production of fMLP or PMA-stimulated U937 cells. IFN-gamma increased the ratio of CD23 and CD11b positive cells. The fluorescence intensity of CD14 and CD25 was enhanced by IFN-gamma treatment. U937 cells produced IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha by lipopolysaccharide (LPS) stimulation. IFN-gamma treatment enhanced TNF-alpha production, but decreased IL-6 production. These results suggest that IFN-gamma differentiates U937 cells to monocyte-like cells and it regulates the production systems of IL-6 and TNF-alpha separately in U937 cells.
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PMID:Effects of interferon-gamma on cell differentiation and cytokine production of a human monoblast cell line, U937. 859 30

The c-rel protooncogene encodes a subunit of the NF-kappa B-like family of transcription factors. Mice lacking Rel are defective in mitogenic activation of B and T lymphocytes and display impaired humoral immunity. In an attempt to identify changes in gene expression that accompany the T-cell stimulation defects associated with the loss of Rel, we have examined the expression of cell surface activation markers and cytokine production in mitogen-stimulated Rel-/- T cells. The expression of cell surface markers including the interleukin 2 receptor alpha (IL-2R alpha) chain (CD25), CD69 and L-selectin (CD62) is normal in mitogen-activated Rel-/- T cells, but cytokine production is impaired. In Rel-/- splenic T cell cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin, the levels of IL-3, IL-5, granulocyte- macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) were only 2- to 3-fold lower compared with normal T cells. In contrast, anti-CD3 and anti-CD28 stimulated Rel-/- T cells, which fail to proliferate, make little or no detectable cytokines. Exogenous IL-2, which restitutes the proliferative response of the anti-CD3- and anti-CD28-treated Rel-/- T cells, restores production of IL-5, TNF-alpha, and IFN-gamma, but not IL-3 and GM-CSF expression to approximately normal levels. In contrast to mitogen-activated Rel-/- T cells, lipopolysaccharide-stimulated Rel-/- macrophages produce higher than normal levels of GM-CSF. These findings establish that Rel can function as an activator or repressor of gene expression and is required by T lymphocytes for production of IL-3 and GM-CSF.
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PMID:Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor. 862 48

Working with the murine epidermal-derived dendritic cell (DC) line XS52, we have observed previously that antigen-specific interaction with T cells stimulates their "terminal maturation" into fully professional DC. In this study we examined the impact of dexamethasone (DEX) on this T cell-induced event. When added to cocultures of XS52 DC and the KLH-specific Th1 clone HDK-1 in the presence of antigen, DEX at relatively low concentrations (10(-9)-10(-7) M) prevented substantially or completely each of the changes that typify terminal maturation, including (a) secretion of relatively large amounts of IL-1beta, IL-6, and TNFalpha; (b) loss of CD115 (colony-stimulating factor-1 receptor) expression and proliferative responsiveness to colony-stimulating factor-1; and (c) elevated expression of CD86 (B7-2). XS52 cells also underwent terminal maturation upon exposure to lipopolysaccharide alone, and DEX also inhibited effectively each of the same changes, indicating that DC can serve as the direct target of DEX. By contrast, DEX inhibited XS52 DC-stimulated IL-2 secretion by HDK-1 T cells, but not other changes that accompany T cell activation, including the secretion of IFNgamma and TNFalpha and the elevated expression of CD25, CD28, and CD44. These results reveal a new immunosuppressive mechanism of glucocorticoid action, that is, direct inhibition of T cell-mediated terminal maturation by DC.
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PMID:A novel mechanism of glucocorticoid-induced immune suppression: the inhibiton of T cell-mediated terminal maturation of a murine dendritic cell line. 869 Jul 86

In order to determine the effects of halothane on rat cell-mediated immune function, rats were exposed to 1% halothane for up to 5 hours. Immediately, 24 hours or 48 hours following anesthesia, rat lymphocytes from the spleen were analyzed for their ability to respond to the mitogens phytohemagglutinin (PHA), pokeweed mitogen (PWM), concanavalin A (ConA) and lipopolysaccharide (LPS). In addition, percentages of lymphocyte subpopulations in the spleen were assessed as well as ability of the lymphocytes to express specific receptors. Extended periods of halothane anesthesia (5 hours) suppressed the ability of the lymphocytes to respond to the mitogen PHA immediately following anesthesia. Twenty-four hours later, proliferative responses to the mitogens PHA, PWM and ConA were significantly reduced. However, by 48 hours following treatment, proliferative responses were normal. Halothane did not alter proliferative responses to the mitogen LPS. Prolonged anesthesia (5 hours) also increased the percentage of T and CD8+ (cytotoxic) lymphocytes in the spleen, although for less than 24 hours. The ability of T lymphocytes to express both the CD8 and CD25 (IL-2) receptors in response to PHA were suppressed. These results suggest that halothane suppresses rat T cell function, perhaps through suppression of IL-2 receptor expression.
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PMID:Halothane inhibits T cell proliferation and interleukin-2 receptor expression in rats. 877 74

Influenza A viruses display T cell-independent polyclonal B cell-activating properties which are mediated by the B cell-superstimulatory envelope glycoprotein hemagglutinin (HA). In this report, the receptor-binding requirements for B cell activation by influenza viruses were expected. Neuraminidase treatment of resting mature B cells from BALB/c mice abrogated late (proliferation/immunoglobulin synthesis), early (up-regulation of cell surface markers, including CD25, B220, and B7-1) and very-early events (homotypic adhesion) in virus-responding B lymphocytes. Similarly, pretreatment of murine responder cells with different inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin) significantly suppressed subsequent B lymphocyte activation by HA, but not control responses to lipopolysaccharide or anti-mu. Assays with chimeric HA transfectants, expressing the loop region of epitope B (amino acids 155-160) of the globular head of H2 (high B cell-stimulatory subtype) or H3 (medium-stimulatory subtype) on the protein backbone of a low-stimulatory subtype (H1) failed to alter the B cell-stimulatory activity of the virus, suggesting that the hypervariable loop region is not crucial in determining the B cell-activating properties of the protein. Collectively, our results imply that the B cell-superstimulatory function of influenza virus HA is not mediated by a direct protein/protein interaction, but via binding of HA to terminal sialic acid residues on cell surface receptor glycoproteins. These findings identify the influenza virus HA glycoprotein as the first viral lectin with lymphocyte-activating properties.
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PMID:Influenza A virus hemagglutinin is a B cell-superstimulatory lectin. 881 51

We have demonstrated recently that Birbeck granule-positive Langerhans cells (LC) can be derived from CD34+ peripheral blood progenitor cells in the presence of a seven-cytokine cocktail (CC7-7). Here, we show that the sequential use of early-acting hematopoietic growth factors, stem cell factor, interleukin (IL)-3, and IL-6, followed on day 8 by differentiation in the two-factor combination IL-4 plus granulocytemacrophage colony-stimulating factor (GM-CSF) (CC4GM) is more efficient and allows the cells to be arrested in the LC stage for more than 1 week while continuous maturation occurs in CC7-7. Maturation of LC to interdigitating dendritic cells (DC) could specifically be induced within 60 hours by addition of tumor necrosis factor-alpha (20 ng/mL) or lipopolysaccharide (100 ng/mL). Using LC that had been enriched to greater than 90% CD1a+ cells by an immunoaffinity column, we were able to define clear-cut differences between LC and DC that corroborate data of the respective cells derived from epithelial borders (LC) or from lymph nodes (LN) and spleen (DC). Thus, molecules and functions involved in antigen (AG) uptake and processing were highly expressed in LC, while those involved in AG presentation were at maximum in DC. LC were CD1a+2 DR+2, CD23+, CD36+, CD80-, CD86-, and CD25-, while DC were CD1a+/- DR+3, CD23-, CD36-, CD80+, CD86+2, and CD25+, CD40 and CD32 were moderately expressed and nearly unchanged on maturation, in contrast to monocyte-derived DC. Macropinocytosis of fluorescein isothiocyanate-dextran was dominant in LC, as were multilamellar major histocompatibility complex (MHC) class II compartments (MIICs), which were detected by electron microscopy. The functional dichotomy of these cell types was finally supported by testing the AG-presenting cell function for tetanus toxoid to primed autologous T-cell lines, which was optimal when cells were loaded with AG as LC and subsequently induced to become DC.
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PMID:In vitro differentiation of CD34+ hematopoietic progenitor cells toward distinct dendritic cell subsets of the birbeck granule and MIIC-positive Langerhans cell and the interdigitating dendritic cell type. 883 46


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