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)

BALB/c spleen cells (5 x 10(6)) were cultured in 1 ml of serum-free RPMI 1640 medium for 3 days in order to examine the effect of cholera enterotoxin (CN) and its spontaneously formed toxoid (CD) on lymphocyte stimulation. Stimulation was assessed after addition of [3H] thymidine for the last 16 hours of culture. One microgram of CN per culture markedly reduced the baseline of [3H] thymidine incorporation and the stimulation due to phytohaemagglutinin (PHA), concanavalin A (con A) and bacterial lipopolysaccharide (LPS). One microgram of CD diminished the base-line to half, abolished the response to PHA, reduced the response to con A and had very little effect on the LPS-induced stimulation. One-tenth the amount (0-1 mug) of both CN and CD affected only the PHA reaction. A secondary response to haemocyanin in vitro was not decreased by this lower dose. The effect of 1 mug on CN on the LPS response could be reduced by pretreatment of the cells with CD, whereas the PHA reaction remained markedly diminished. Dibutyryl-cAMP added to culture tubes had a similar effect ot 1 mug of CN, affecting the PHA response much more than the response to LPS. Spleen cells of mice immunized with CD gave a significant proliferative response to both 1 mug of CD and CN. The results are interpreted as indicating a strong inhibitory effect of CN mediated by accumulation of intracellular cAMP. CD-immunized cells contain specific receptors for both CD and CN which probably compete with the sites responsible for adenylate cyclase stimulation by CN.
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PMID:The differential effect of cholera toxin on the lymphocyte stimulation induced by various mitogens. 16 98

The effects of thymosin and lipopolysaccharide (LPS) on cyclic AMP levels in lymphocytes were evaluated using three independent assays which included adenine prelabeling, protein kinase binding, and radioimmunoassay. All three assays proved to be both sensitive and accurate in assessing relative changes in lymphocytes after incubation in vitro with various agents. The assays confirmed that basal and stimulated levels of cyclic AMP depended on the origin of the lymphocyte population. Each of the three techniques demonstrated that pyrogen-free bovine thymosin fraction 5 did not elevate thymocyte cAMP levels. In contrast, it was found that lipopolysaccharide (lps) significantly elevated cAMP levels in both spleen and thymus lymphocytes. These studies indicate that assays for measuring the activity of thymic extracts in which the intracellular levels of cyclic nucleotides are a criterion for activity are only valid if the preparations are not contaminated with endotoxins.
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PMID:Effect of thymosin and lipopolysaccharide on murine lymphocyte cyclic AMP. 20 27

Responses of blood platelets to bacterial endotoxin lipopolysaccharide (LPS) have been correlated with changes in the molecular organization and composition of the platelet plasma membrane proteins. Binding of LPS, which occurred in the absence of Ca2+, was distinguished from platelet aggregation and degranulation, which required Ca2+ and plasma proteins. Changes in membrane organization were detected by double-labelling with [125I] and [131I] iodide, mediated by lactoperoxidase and hydrogen peroxide. Changes in total membrane composition were detected by gel electrophoresis of isolated membranes. Binding of LPS was associated with increased accessibility of a protein of mol. wt. 80000 to iodination. After aggregation and degranulation there was, in addition, increased accessibility of proteins of mol. wt. 68000 and 48000. Isolated membranes from LPS-stimulated platelets contained more of a protein of mol. wt. 200000 and less of a protein of mol. wt. 220000 than control membranes prepared from unstimulated platelets in the presence of cAMP and aminophylline. The relationship of the modified plasma membrane proteins to the contractile proteins of the platelet and their possible redistribution in the cell during aggregation and secretion is discussed.
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PMID:Endotoxin-induced platelet aggregation and secretion. II. Changes in plasma membrane proteins. 59 72

Lucifer yellow (LY) accumulation was used to measure macrophage pinocytosis. The hematopoietic growth factors, macrophage colony-stimulating factor (CSF-1), granulocyte-macrophage CSF (GM-CSF), and interleukin 3, and the macrophage activators, lipopolysaccharide and zymosan, all stimulated LY uptake in both murine bone marrow-derived macrophages (BMMs) and resident peritoneal macrophages (RPMs) without affecting LY efflux. The stimulation of pinocytosis in the poorly cycling RPMs and in BMMs by nonmitogens dissociates stimulation of pinocytosis from subsequent DNA synthesis. Regulation of pinocytosis in BMMs appears to be independent of that of urokinase-type plasminogen activator expression. The increases in CSF-mediated BMM pinocytosis were not inhibited by pertussis toxin, by elevations in intracellular cAMP, or by glucocorticoids and were only partially inhibited by inhibitors of Na+/H+ antiport and Na+/K(+)-ATPase activities. Protein kinase C activation could be involved in regulating BMM pinocytosis because phorbol myristate acetate, oleoylacyglycerol, and exogenously added phospholipase C can all stimulate it. Ca2+ ionophores were inactive, whereas the Na+/H+ ionophore monensin potently inhibited BMM pinocytosis.
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PMID:Regulation of pinocytosis in murine macrophages by colony-stimulating factors and other agents. 131 79

Different macrophage preparations were compared for functional capacity in conditions of high prostaglandin E2 (PGE2) or low L-arginine concentrations. Macrophages derived in vitro from bone marrow progenitor cells (bone marrow-derived macrophages, BMDMs) using colony-stimulating factor 1 (CSF-1) as the myelopoietic stimulus displayed a greater sensitivity to PGE2-induced suppression of tumor necrosis factor alpha (TNF-alpha) secretion than did macrophages derived using granulocyte-macrophage colony-stimulating factor (GM-CSF). Neither BMDM population was inhibited by PGE2 for the direct cytolysis of L929 cells (TNF-alpha sensitive), and only GM-CSF-derived macrophages showed decreased killing of TNF-alpha-resistant K562 targets. Exogenous cAMP inhibited TNF-alpha secretion, but not nitrite secretion, by both BMDM populations. GM-CSF-derived macrophages accumulated less cAMP following PGE2 treatment than did CSF-1-derived macrophages. Removing L-arginine from the medium did not inhibit cytotoxicity or PGE2 secretion, but the listeriacidal activity specific to interferon-gamma plus lipopolysaccharide (LPS)-activated GM-CSF-derived macrophages was blocked by removal of L-arginine. Treatment with CSF-1 or GM-CSF alone did not activate the macrophages, but GM-CSF efficiently primed both BMDM populations for augmented TNF-alpha secretion in response to secondary stimulation using LPS. However, GM-CSF augmented the LPS-induced production of nitrite and PGE2 by CSF-1-derived macrophages only. These results demonstrate the potential for differential macrophage function within inflammatory sites based on the hematopoietic stimulus under which the macrophage is derived and the specific conditions present in the lesion.
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PMID:Macrophage function in response to PGE2, L-arginine deprivation, and activation by colony-stimulating factors is dependent on hematopoietic stimulus. 132 89

Nitric oxide (NO), apart from its properties as a vasodilator, is a cytotoxic agent released from macrophages upon stimulation with immunomodulating agents such as interferon-gamma and endotoxin. In rat Kupffer cells endotoxin causes the release of NO as well as of tumor necrosis factor-alpha and prostaglandin E2 (PGE2). This eicosanoid and its second messenger, cyclic AMP, have been shown to increase nitric oxide formation in Kupffer cells treated with endotoxin (Gaillard et al. (1991) Pathobiology 59, 280-283). But not only added PGE2 but also the prostaglandin produced endogenously upon stimulation with endotoxin increases NO synthesis. Neither tumor necrosis factor-alpha nor interleukin-1 beta stimulate NO synthesis by themselves, but together with PGE2 they are as effective as lipopolysaccharide plus PGE2. To replace PGE2 in the combination with the cytokines, however, dibutyryl cAMP has to be present in higher concentrations than with LPS. Interleukin-6 alone or in combination with PGE2 or dibutyryl cAMP is without any effect. Anti-TNF-alpha as well as anti-PGE2 antibodies reduce the release of NO upon stimulation with LPS. Consequently, the effect of LPS on NO production seems to be in part due to the self-stimulating effect of PGE2 and some cytokines, both produced by Kupffer cells upon LPS stimulation.
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PMID:Regulation by prostaglandin E2 of cytokine-elicited nitric oxide synthesis in rat liver macrophages. 133 72

Agents that can arrest cellular proliferation are now providing insights into mechanisms of growth factor action and how this action may be controlled. It is shown here that the macrophage activating agents tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma), and lipopolysaccharide (LPS) can maximally inhibit colony stimulating factor-1 (CSF-1)-induced, murine bone marrow-derived macrophage (BMM) DNA synthesis even when added 8-12 h after the growth factor, a period coinciding with the G1/S-phase border of the BMM cell cycle. This inhibition was independent of autocrine PGE2 production or increased cAMP levels. In order to compare the mode of action of these agents, their effects on a number of other BMM responses in the absence or presence of CSF-1 were examined. All three agents stimulated BMM protein synthesis; TNF alpha and LPS, but not IFN gamma, stimulated BMM Na+/H+ exchange and Na+,K(+)-ATPase activities, as well as c-fos mRNA levels. IFN gamma did not inhibit the CSF-1-induced Na+,K(+)-ATPase activity. TNF alpha and LPS inhibited both CSF-1-stimulated urokinase-type plasminogen activator (u-PA) mRNA levels and u-PA activity in BMM, whereas IFN gamma lowered only the u-PA activity. In contrast, LPS and IFN gamma, but not TNF alpha, inhibited CSF-1-induced BMM c-myc mRNA levels, the lack of effect of TNF alpha dissociating the inhibition of DNA synthesis and decreased c-myc mRNA expression for this cytokine. These results indicate that certain biochemical responses are common to both growth factors and inhibitors of BMM DNA synthesis and that TNF alpha, IFN gamma, and LPS, even though they all have a common action in suppressing DNA synthesis, activate multiple signaling pathways in BMM, only some of which overlap or converge.
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PMID:Biochemical events accompanying macrophage activation and the inhibition of colony-stimulating factor-1-induced macrophage proliferation by tumor necrosis factor-alpha, interferon-gamma, and lipopolysaccharide. 133 37

(+)-Pentazocine, phencyclidine, and other sigma ligands including 1,3-di-(o)-tolylguanidine (DTG), (+)-1-propyl-3-(3-hydroxyphenyl) piperidine [(+)-PPP] and haloperidol were investigated for their potential immunoregulatory properties. High concentrations (10(-5) M) of DTG and haloperidol were found to suppress in vitro murine splenocyte natural killer activity while equivalent concentrations of (+)-pentazocine, (-)-pentazocine and (+)-PPP were without effect. In a reciprocal fashion, lower doses (10(-9) M) of DTG enhanced natural killer activity. Sigma ligands were also found to affect in vitro polyclonal immunoglobulin production following mitogen stimulation. Specifically, high concentrations (10(-6) M) of haloperidol significantly (P < 0.001) suppressed pokeweed mitogen (PWM)-stimulated IgG and IgM production, yet enhanced lipopolysaccharide (LPS)-stimulated IgM production by murine splenocytes. Lower concentrations (10(-8) to 10(-10) M) enhanced (two- to fourfold) PWM-induced IgM production and LPS-stimulated IgG and IgM production. At high concentrations (10(-6)), (+)-pentazocine suppressed (P < 0.01) LPS-induced polyclonal IgG and IgM but enhanced (P < 0.01) PWM-induced IgM production. Both DTG and (-)-pentazocine (10(-8) to 10(-10) M) significantly augmented (two- to threefold) LPS-stimulated murine splenocyte production of polyclonal IgM. Intracellularly, (-)-pentazocine (10(-9) M), haloperidol (10(-7) M), DTG (10(-7) M) and (+)-PPP (10(-5) to 10(-9) M) enhanced forskolin (10(-6) M)-induced cAMP production in splenic lymphocytes while (+)-pentazocine was without effect. Collectively, the data suggest functional and biologically relevant sigma receptors on cells of the immune system.
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PMID:Immunoregulatory properties of (+)-pentazocine and sigma ligands. 149 25

A recently identified novel mammalian cyclin (CYL1), induced by growth factors and apparently functional during the G1 phase of the cell cycle, is of potential significance, given that cell division is primarily controlled in G1. We have measured CYL1 gene expression in murine bone marrow-derived macrophages (BMM), a normal cell type dependent upon colony-stimulating factors (CSFs) for survival and proliferation. The induction of CYL1 mRNA levels correlated strongly with stimulation of DNA synthesis, since elevated CYL1 mRNA levels occurred in response to the mitogenic stimuli, CSF-1, and granulocyte/macrophage CSF, but not to nonmitogenic macrophage-activating agents. BMM are subject to cell cycle arrest by numerous agents, including tumor necrosis factor alpha, interferon gamma, bacterial lipopolysaccharide, and agents that increase cAMP. These antiproliferative agents suppressed CSF-1-stimulated CYL1 gene expression, even when added late in G1. This pattern of CYL1 gene expression was remarkably consistent with the ability of these agents to inhibit progression into S phase. The mechanisms of negative growth regulation are largely unknown, and given the likely importance of G1 cyclins in the control of cell division, we propose that antiproliferative agents may exert their effects by suppressing G1 cyclin gene expression.
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PMID:Suppression of growth factor-induced CYL1 cyclin gene expression by antiproliferative agents. 153 6

Natural infection by mouse hepatitis virus (MHV) can affect interpretation of immunological studies in mice. MHV, a collective term describing a group of corona viruses, is found in natural infections in over 70% of laboratory mouse populations in the U.S.A. and Canada. Natural outbreaks of MHV in our animal colony afforded us the opportunity to study MHV-induced immunosuppression as well as the effects of MHV infection on neurotransmitter immunomodulation. Concanavalin A (Con A)-stimulated DNA synthesis by spleen T lymphocytes from MHV-infected mice was 20-50% that of non-infected mice. The MHV infection also altered neurotransmitter modulation of spleen T-lymphocyte activation. In contrast to noradrenaline ablation of Con A-activated DNA synthesis by spleen lymphocytes from non-infected mice, DNA synthesis by the infected group was not inhibited by noradrenaline or dibutyryl-cAMP. These effects of MHV infection were specific for spleen T lymphocytes since MHV infection did not alter Con A stimulation of thymocytes, lipopolysaccharide stimulation of spleen B lymphocytes, or noradrenaline inhibition of thymocyte and B-cell DNA synthesis. MHV infection also did not alter spleen T-lymphocyte subset proportions. Thus, MHV infection inhibits spleen T-lymphocyte activation and blocks in vitro catecholamine and cAMP regulation of spleen T-cell activation but does not affect activation of thymic cells or spleen B cells.
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PMID:Mouse hepatitis virus infection suppresses modulation of mouse spleen T-cell activation. 157


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