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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that subcutaneous injection of casein, a potent inducer of the immunomodulatory acute phases reactant, serum amyloid A (SAA) protein, produces a marked suppression of humoral responses that require macrophage accessory cell cooperativity in the B6C3F1 mouse. The objective of these studies was to further characterize the immunological changes produced by casein treatment. It was observed that the inhibition of the sRBC IgM AFC response which accompanies casein treatment is dose related to the amount of casein introduced subcutaneously to the mouse. These studies, as well as those previously reported by several laboratories including our own have demonstrated that spleen cells isolated from casein-treated mice also exhibit markedly suppressed humoral responses in vitro. However, casein added directly to naive spleen cell cultures at concentrations significantly higher than those which would be found in the lymphoid tissues of the intact animal have no direct inhibitory effect on the sRBC IgM AFC response, suggesting that casein alone does not exert a direct immunosuppressive effect. Kinetics of recovery studies indicate that the casein-induced immunosuppression is readily reversible. Humoral responses are fully recovered within 3 days, once subcutaneous injections of casein are terminated. In vitro measurements of IL-1 secretion following stimulation of splenic macrophages, isolated from casein treated mice, with lipopolysaccharide indicate no significant effect on the capacity of these cells to produce this cytokine. Direct addition of recombinant IL-1 or interferon-gamma to spleen cell cultures isolated from casein-treated mice also was found to be incapable of reversing the inhibited IgM AFC response. Taken together, these studies strongly suggest that the accessory cell dysfunction associated with macrophages from casein-treated mice is not due to the inability of these cells to secrete IL-1 and indicate that the dysfunction cannot be reversed by IL-1 or interferon-gamma. Casein treatment was also found to markedly inhibit DTH, a cell-mediated immune response requiring macrophage accessory cell function. interestingly, the DTH responses were only affected by casein when it was administered post-sensitization with antigen (sRBC) but prior to antigen challenge. When casein was administered prior to sensitization with antigen, which is analogous to the treatment schedule that was found to suppress the sRBC antibody response, no effect was observed on DTH.
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PMID:A functional characterization of macrophage alterations in casein-treated B6C3F1 mice. 147 55

Supernatants collected from cisplatin, lipopolysaccharide (LPS), muramyl dipeptide (MDP) or interferon-gamma (IFN-gamma) treated human monocytes enhance the thymocyte proliferation by a submitogenic concentration of concanavalin A. Also supernatants collected from cisplatin or IFN-gamma treated monocytes demonstrated enhanced cytotoxicity against actinomycin-D treated L 929 cells, suggesting that cisplatin or rIFN-gamma treated monocytes release tumor necrosis factor (TNF) into the culture medium. The supernatant collected from untreated monocytes showed only little IL-1 and TNF activity.
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PMID:Increased production of interleukin-1 and tumor necrosis factor by human monocytes treated in vitro with cisplatin or other biological response modifiers. 148 5

Membrane currents of cultured rat microglia were recorded with the whole-cell patch clamp technique. Undifferentiated microglia express only inwardly rectifying K+ channels. However, treatment of the cells with bacterial lipopolysaccharide, interferon-gamma, or their incubation in hydrophobic teflon bags, procedures that promote microglial differentiation, induced the expression of an additional outward current. Cycloheximide prevented the development of this conductance indicating the synthesis of a new channel protein. The reversal potential of the outward current was near to the K+ equilibrium potential; the current was abolished by intracellular Cs+ or extracellular 4-aminopyridine, and was depressed by extracellular tetraethylammonium. Hence, the channels involved appear to be highly selective for K+; their possible function is a rapid termination of depolarizing shifts of the membrane potential.
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PMID:Inflammatory stimuli induce a new K+ outward current in cultured rat microglia. 149 2

The role that inflammatory cytokines may play in the life cycle of the hepatitis B virus and in the pathogenesis of its associated liver disease has not been carefully delineated. In this report, we demonstrate that bacterial lipopolysaccharide, a potent inducer of inflammatory cytokines in vivo, causes a severe acute liver disease in transgenic mice whose hepatocytes produce the hepatitis B virus large envelope polypeptide and retain HBsAg within the endoplasmic reticulum. In contrast, 100-fold higher doses of bacterial lipopolysaccharide do not induce liver cell injury in nontransgenic littermate controls or in transgenic mice whose hepatocytes secrete HBsAg rather than retain it. Coincident with the hepatocellular injury and the influx of inflammatory cells into the liver, a marked reduction occurs in the intrahepatic content of hepatitis B virus steady-state messenger RNA, thereby confirming the selectivity of this process for the HBsAg-positive hepatocyte. Bacterial lipopolysaccharide-induced hepatocellular injury appears to be principally mediated by interferon-gamma because it can be markedly reduced by the prior administration of neutralizing interferon-gamma-specific monoclonal antibodies and because recombinant interferon-gamma is also selectively cytotoxic for the HBsAg-positive transgenic hepatocyte in vivo. Tumor necrosis factor-alpha is also involved in this process because bacterial lipopolysaccharide-induced liver cell injury is significantly reduced by tumor necrosis factor-alpha specific monoclonal antibodies. The role of tumor necrosis factor-alpha in bacterial lipopolysaccharide-induced liver cell injury is less clear than interferon-gamma, however, because unlike interferon-gamma it is also toxic for nontransgenic hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HBsAg retention sensitizes the hepatocyte to injury by physiological concentrations of interferon-gamma. 150 8

Phytohemagglutinin (PHA) injection induces transient protease-sensitive traffic of lymphocytes in skin and other tissues in several species. Examination of the possible roles of cytokines in such reactions showed that recombinant bovine and human tumor necrosis factor (TNF)-alpha potently induce dose-dependent lymphocyte traffic in pig skin (and in other tissues including the draining lymph nodes) with early kinetics and a morphology of the inflammatory reaction similar to that of PHA (peaking 9-12 h). Recombinant human interleukin (IL)-1 alpha also induces dose-dependent lymphocyte traffic, but it peaks at 4 h. Entry of labeled lymphocytes into inflammatory sites induced by PHA, TNF-alpha and IL-1 alpha, but not into normal skin, is inhibited by approximately 80% by their pretreatment with trypsin, indicative of the induction of endothelial determinants recognized by protease-sensitive surface molecules on the lymphocytes. Even the minimal lymphocyte traffic induced by interferon-gamma and lipopolysaccharide was similarly protease sensitive. At the earliest stage (approximately 2 h) of significant induction of lymphocyte entry by TNF-alpha and IL-1 alpha the inductive signal for each appears easily saturated. Thus lymphocyte entry is little increased by increasing low cytokine doses over 100-fold: However, these reactions are additive, and this was used to confirm that they are distinct from each other and from PHA. A further distinction was revealed by the homing of lymphocytes pretreated with pertussis toxin: such lymphocytes were greater than 90% inhibited in their homing to tissues through constitutive high endothelial venules (HEV) and greater than 60% inhibited in homing to TNF-alpha and IL-1 alpha skin sites, but unaffected in homing to PHA skin sites (like most non-HEV-mediated traffic). Moreover, potent chicken anti-TNF-alpha, which prevented TNF-induced lymphocyte entry, did not affect PHA-induced traffic. Thus, these three agents which induce peripheral lymphocyte traffic appear to involve different mechanisms as shown by differences in (i) their kinetics; (ii) the effect of anti-TNF-alpha and (iii) the effect of pertussis toxin treatment of the lymphocytes and by the fact that their inductive mechanisms are additive in effect.
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PMID:Active lymphocyte traffic induced in the periphery by cytokines and phytohemagglutinin: three different mechanisms? 151 13

Four patients with ovarian cancer received 20 mg of sizofiran, a beta-1,3-glucan (molecular weight: 450,000), intramuscularly one day before and 4, 7, 11, 14, 18 and 21 days after second look laparotomy and recombinant interferon-gamma (rIFN-gamma) intraperitoneally on the day of second look laparotomy and 4, 7, 11, 14, 18 and 21 days thereafter. The peritoneal cavity was washed with physiological saline and peritoneal macrophages (M phi) were isolated. The number of M phi increased 30-1600 times during the treatment period. The concentrations of interleukin-1, interferon-gamma, tumor necrosis factor and prostaglandin E2 were also found increased in the supernatant fluid of M phi cultured for 24 hours with 10 micrograms/ml of lipopolysaccharide. The present study demonstrated that the activation of peritoneal M phi could be maintained and its number was increased by repeated dosing of sizofiran and rIFN-gamma in combination every three or four days in patients with ovarian cancer. Peritoneal M phi thus activated may exert an antitumor effect on ovarian cancer.
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PMID:Maintenance of the activation of peritoneal macrophages in patients with ovarian cancer by sizofiran and recombinant interferon-gamma. 152 54

Cytokines have been implicated in the pathogenesis of gram-negative bacterial meningitis. The effects of pentoxifylline and dexamethasone on the release of tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6 from primary murine microglial cell cultures were explored using bioassays. When added concomitantly with lipopolysaccharide, pentoxifylline blocked the release of TNF and IL-1 but not IL-6, while dexamethasone inhibited the release of TNF and IL-6. After a 2-h exposure of microglia to lipopolysaccharide, pentoxifylline but not dexamethasone still inhibited the release of TNF. Release of TNF was enhanced 20-fold by priming of the microglia with interferon-gamma; only pentoxifylline blocked the priming effect of interferon-gamma on TNF release. These results demonstrate that pentoxifylline and dexamethasone differentially regulate the release of cytokines in microglial cell cultures and provide potential insight into their role in the treatment of gram-negative bacterial meningitis.
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PMID:Cytokine release from microglia: differential inhibition by pentoxifylline and dexamethasone. 152 22

Mouse peritoneal macrophages activated with interferon-gamma (IFN-gamma) and lipopolysaccharide produce substantial amounts of nitric oxide (NO), which correlates with the elimination of the intracellular protozoan parasite Leishmania major. Both the production of NO and the leishmanicidal function of the activated macrophages can be significantly inhibited by catalase in a dose- and time-dependent manner. These results could not be interpreted by the reduction of H2O2 by catalase since the removal of H2O2 by the addition of glutathione peroxidase had no effect on the NO synthesis or the leishmanicidal function of activated macrophages. Furthermore, catalase did not affect the induction of NO synthase in IFN-gamma-activated macrophages. In contrast, the inhibition of NO synthesis and leishmanicidal activity by catalase was reversed in a dose-dependent manner by the addition of tetrahydrobiopterin, a cofactor of NO synthase. Taken together, these results not only further support the central role of NO as the cytotoxic moiety, but also suggest that hydrogen peroxide may interfere with NO production by affecting the levels of cofactor needed for its synthesis.
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PMID:Catalase inhibits nitric oxide synthesis and the killing of intracellular Leishmania major in murine macrophages. 153 80

Isolated rat brain microglia display enhanced expression of Fc receptors on treatment with interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and lipopolysaccharide (LPS), whereas major histocompatibility complex (MHC) antigen expression is enhanced only by IFN-gamma. Although TNF and LPS individually have no effect on MHC expression by microglia, they both antagonize IFN-gamma-induced expression. The enhanced expression of Fc receptors observed in the presence of IFN-gamma, TNF or LPS is significantly inhibited by the combination of IFN-gamma with either LPS or TNF. IL-1 alpha has little effect on IFN-gamma-induced MHC or Fc receptor expression by microglia. Peritoneal macrophages behave similarly to microglia, with the notable exception that IL-1 alpha enhances IFN-gamma-induced FcR expression. These observations suggest that the functional activity of microglia during inflammation or demyelination in the central nervous system can be influenced by the changing profile of cytokines present during lesion development.
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PMID:Regulation of Fc receptor and major histocompatibility complex antigen expression on isolated rat microglia by tumour necrosis factor, interleukin-1 and lipopolysaccharide: effects on interferon-gamma induced activation. 153 93

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


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