Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results suggested that immunotoxicity induced by lead [Pb, as Pb(NO(3))(2)] was significantly restored or prevented by melatonin (MLT). MLT (10 or 50 mg/kg) was orally administered to ICR mice daily for 28 days, and Pb was also administered at 35 mg/kg in the same way 2 h after the administration of MLT, and the normal mice were given vehicle. Within the Pb plus MLT-treated group, the body weight gains and the relative thymus weights were significantly increased when compared with the treatment of Pb alone. The relative spleen and liver weights were increased by the treatment of Pb alone, and then restored to normal value by MLT treatment. Hemagglutination (HA) titer, plaque-forming cell response to sheep red blood cell (SRBC), and secondary IgG antibody response to BSA were significantly enhanced in the Pb plus MLT-treated mice, as opposed to when compared with the treatment of Pb alone. The mitogenic response of splenic T cell to concanavalin A and that of B cells to lipopolysaccharide was remarkably increased by MLT treatment when compared with treatment of Pb alone. Splenic CD4(+)cells were significantly increased by MLT treatment when compared with treatment of Pb alone. In case of CD8(+) cells, the slight enhancement was observed in MLT treatment. Splenic T and B cells were significantly increased by MLT treatment when compared with the treatment of Pb alone. The natural killer cell, phagocytic activity and the number of peripheral leukocytes were significantly enhanced in Pb plus MLT-treated mice when compared with the treatment of Pb alone.
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PMID:Influence of melatonin on immunotoxicity of lead. 1096 54

The glycosylphosphatidylinositol-anchored receptor CD14 plays a major role in the inflammatory response of monocytes to lipopolysaccharide. Here, we describe that ceramide, a constituent of atherogenic lipoproteins, binds to CD14 and induces clustering of CD14 to co-receptors in rafts. In resting cells, CD14 was associated with CD55, the Fcgamma-receptors CD32 and CD64 and the pentaspan CD47. Ceramide further recruited the complement receptor 3 (CD11b/CD18) and CD36 into proximity of CD14. Lipopolysaccharide, in addition, induced co-clustering with Toll-like receptor 4, Fcgamma-RIIIa (CD16a) and the tetraspanin CD81 while CD47 was dissociated. The different receptor complexes may be linked to ligand-specific cellular responses initiated by CD14.
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PMID:Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts. 1174 32

Lactoferrin is an iron-binding glycoprotein present in various secretions (eg. milk, tears, saliva,pancreatic juice, etc.). It is also stored in specific granules of polymorphonuclear granulocytes from which it is released following activation. Lactoferrin exerts a bactericidal activity by damaging the outermembrane of Gram-negative bacteria, as well as immunoregulatory functions by decreasing the release of interleukin-l (IL- 1), IL-2 and tumor necrosis factor-alpha INF-alpha) and enhancing monocyte and natural killer cell cytotoxicity. Lactoferrin binds with high affinity to lipid A, the toxic moiety of the lipopolysaccharide, or endotoxin from Gram-negative bacteria Lipopolysacchride interaction with monocytes/ma phages results in the production and release of TNF-alpha, that plays an important role in inducing septic shock In this respect, it has recently been demonstrated that lactoferrin inhibits the lipopolysaccharide interaction with CD14 on monocytes/macrophages by competition with the lipopolysaccharide binding protein. Therefore, besides its bactericidal activity, lactoferrin may also act by neutralizing the toxic effects of lipopolysaccharide and this protective role against endotoxin lethal shock has been demonstrated in animal models. Moreover, in vitro and in vivo neutralization of endotoxin by a human lactoferrin-derived peptide was also reported and lactoferrin or lactoferrin-derived peptides could represent useful tools for the treatment of endotoxin-induced septic hock. The recent production and characterization of monoclonal antibodies against different epitopes of human lactoferrin, including monoclonal antibodies selectively neutralizing lactoferrin binding to lipid A, may allow a better elucidation of the consequence of lactoferrin-lipopolysaccharide interaction.
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PMID:Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application. 1254 52

The signal pathways that trigger tumor cell escape from immune surveillance are incompletely understood. Toll-like receptors (TLRs), which activate innate and adaptive immune responses, are thought to be restricted to immune cells. We show here that TLRs, including TLR4, are expressed on tumor cells from a wide variety of tissues, suggesting that TLR activation may be an important event in tumor cell immune evasion. Activation of TLR4 signaling in tumor cells by lipopolysaccharide induces the synthesis of various soluble factors and proteins including interleukin-6, inducible nitric oxide synthase, interleukin-12, B7-H1, and B7-H2, and results in resistance of tumor cells to CTL attack. In addition, lipopolysaccharide-stimulated tumor cell supernatants inhibit both T cell proliferation and natural killer cell activity. Blockade of the TLR4 pathway by either TLR4 short interfering RNA or a cell-permeable TLR4 inhibitory peptide reverses tumor-mediated suppression of T cell proliferation and natural killer cell activity in vitro, and in vivo, delays tumor growth and thus prolongs the survival of tumor-bearing mice. These findings indicate that TLR signaling results in a cascade leading to tumor evasion from immune surveillance. These novel functions of TLRs in tumor biology suggest a new class of therapeutic targets for cancer therapy.
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PMID:Toll-like receptors on tumor cells facilitate evasion of immune surveillance. 3141 49

Irinotecan hydrochloride shows much different responses in each patient, and it has severe adverse effects. Therefore, a sensitive marker for the side effect of irinotecan on immunotoxicity may be able to prevent the severe complications by the early detection. We have recently developed a method to assess the immunotoxicity by measuring the productivity of TNF-alpha from whole blood containing monocytes when stimulated by lipopolysaccharide. By using this method, the effects of continuous low-dose irinotecan therapy on immunotoxicity were assessed in 10 patients with advanced gastric or colon cancer. When compared this method with the others such as white blood cell count, lymphocyte blastoid transformation by phytohem agglutinin (PHA), and natural killer cell activity in terms of the sensitivity, immunotoxicity by this method was found earlier than the other methods. Because our original method is easy to perform and sensitive as compared to the conventional methods, it can be widely used as one of the laboratory tests useful for patients treated with immunosuppressive agents.
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PMID:[Assessment of immunotoxicity of irinotecan determined by the novel method, by which productivity of TNF-alpha from whole blood is stimulated by lipopolysaccharide]. 1610 27

Obesity is a rising problem in cats. It is a risk factor for several diseases and has been linked to impaired immunity. The goal of this study was to determine the effect of body composition and effects of diet on immune function in cats. Twenty-eight short-term obese and 12 lean cats with equal gender distribution were evenly and randomly divided into two groups which were either fed a diet containing saturated (SFA) or long-chain n-3 polyunsaturated fatty acids (3-PUFA) for a period of 6 months prior to testing. Blood was collected by venipuncture from the jugular vein. Blood samples were analyzed in a double blind fashion. A complete blood count was performed and lymphocyte distribution was examined by flow cytometric analysis with specific fluorescein-conjugated subset markers. Immune function was measured as follows: the proliferative activity of different cellular fractions was tested with polyclonal mitogens such as lipopolysaccharide (LPS), phytohaemagglutinin (PHA), phorbol 12-myristate 13-acetate (PMA), Ca ionophore, and concanavalin A. Innate immune functions assessed were phagocytosis and natural killer cell (NK) cytotoxicity. A similar immune innate and adaptive immune response was elicited regardless of diet or body condition. However, there was no correlation between body condition, diet, and any of the quantitative and qualitative functional responses of the immune system. We conclude that short-term obesity and the fatty acid composition of the diet do not alter immune responses in cats.
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PMID:The effects of obesity and fatty acids on the feline immune system. 1806 76

Responding for rewarding brain stimulation has been used to track hedonic status in animals. In addition to neurochemical alterations, stimulation of the lateral hypothalamus or ventral tegmentum has been shown to influence immunological processes, including elevation of peripheral natural killer cell activity. In the present study, we examined whether ventral tegmental area (VTA) stimulation or environmental enrichment altered the severity of lipopolysaccharide (LPS)-induced sickness behaviors and the provocation of cytokine expression induced by the endotoxin. Accordingly, rats received either trials of brain stimulation reward or exposure to an enriched environment and subsequently challenged with 150 ug/kg i.p. of LPS. Groups receiving LPS and saline injections without further manipulation were also included. Using the real-time RT-PCR and a multiplex bead assay, mRNA and protein levels for several cytokines and their receptors were determined to evaluate how these may vary as a consequence of reward. Both brain stimulation and environmental enrichment similarly diminished sickness behaviors associated with the endotoxin. Receptor gene levels were generally stable across groups. Levels of IL-6 within the VTA were increased in the group receiving LPS challenge alone and environmental enrichment was associated with modestly reduced IL-6 levels within this brain region. Taken together, these data suggest that rewarding brain stimulation and environmental enrichment buffer against malaise provoked by endotoxin challenge. Moreover, IL-6 expression within the VTA may influence the development of sickness behavior following inflammatory stimuli.
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PMID:The effects of rewarding ventral tegmental area stimulation and environmental enrichment on lipopolysaccharide-induced sickness behavior and cytokine expression in female rats. 1851 Oct 25

Lobomycosis (Lacaziosis) occurs only in humans and dolphins under natural conditions. We evaluated the immune status of eight dolphins with lobomycosis and 40 healthy dolphins from the Indian River Lagoon (IRL), Florida. Lobomycosis cases had multiple abnormalities in their immunologic parameters when compared to healthy dolphins. The absolute number of circulating lymphocytes and serum albumin concentration were reduced (P<0.05) while the segmented neutrophils, alpha 1, total beta, total gamma and total globulins were increased (P<0.05). Although innate immunity was relatively intact and phagocytosis and natural killer cell activity were not affected, the plasma lysozyme concentrations were elevated in dolphins with lobomycosis (P<0.05). Adaptive immunity was depressed with statistically significant decreases found in the absolute numbers of CD4(+) helper T cells and CD19(+) and CD21(+) B cells. The ratios of CD2(+) T cells to CD4(+) cells and CD2(+) to CD21(+) cells were increased (P=0.05 and P<0.05, respectively) and the numbers of lymphocytes expressing MHC class II molecules was decreased in dolphins with lobomycosis (P<0.05). Lymphocyte proliferation was reduced in response to stimulation with lipopolysaccharide and concanavalin A (P<0.05). Antibody titers to Erysipelas rhusiopathiae, a common marine micro-organism, were decreased (P<0.05). In summary, dolphins with lobomycosis exhibit significant impairment in adaptive immunity.
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PMID:Immune dysfunction in Atlantic bottlenose dolphins (Tursiops truncatus) with lobomycosis. 1860 90

Picrorhiza scrophulariiflora is a traditionally used herb for the treatment of various diseases, including tumors and liver infections. In the present report, one glycoside from the methanol extract of Picrorhiza scrophulariiflora, scrocaffeside A, shows immunomodulatory properties by structure. So we measured various indicators of mammalian immune cells to test its immunostimulation potential. The scrocaffeside A enhanced proliferation of splenocytes and their response to polyclonal T cell mitogen concanavalin A (Con A) and lipopolysaccharide (LPS). There was also a significant increase in the activity of peritoneal macrophages and natural killer cell when treated with doses of scrocaffeside A between 5 microg/ml and 125 microg/ml. A dose-dependent increase was also observed in the populations of mature T cell subsets. The production of cytokines and the CD4/CD8 population of splenocytes were also elevated. The levels of interleukin (IL)-2, IL-4, IL-12, and (IFN)-gamma expressed by cultured splenocytes were significantly increased when the cells were exposed to scrocaffeside A. These results indicate that scrocaffeside A may exert immunoenhancement effects on immune system. In addition to its traditional use in some diseases, it may become a new immunostimulating agent in the future.
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PMID:Effects of scrocaffeside A from Picrorhiza Scrophulariiflora on immunocyte function in vitro. 1969 4

Many traditional Chinese medicines have been used as immunomodulators that act as either immunosuppressants or immunostimulators. Recently, our lab successfully isolated a monomer telocinobufagin (TCB) from the chloroform extract of Chan Su (Venenum Bufonis). In the present paper, we evaluated the immunomodulatory effects of this compound in vitro. We found that TCB significantly stimulates splenocyte proliferation when administered alone or in combination with polyclonal T-cell mitogens concanavalin A (Con A) and lipopolysaccharide. Telocinobufagin markedly enhances natural killer cell and peritoneal macrophage activation. Telocinobufagin increases the percentage of CD4, CD8 positive cells within a population of splenocytes. Moreover, we found that the level of several Th1 cytokines, including interleukin-2 (IL-2), interleukin-12 (IL-12), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), are significantly increased after TCB treatment, while the level of the Th2 cytokine interleukin-4 (IL-4) is significantly decreased. As a result, the ratio of Th1/Th2 is significantly increased. Taken together, these results indicate that TCB has potential immune system regulatory effects and suggest that this compound could be developed as a novel immunotherapeutic agent to treat cancer and other immune-mediated diseases, and it may become a new immunomodulatory agent in many regions.
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PMID:The effects of telocinobufagin isolated from Chan Su on the activation and cytokine secretion of immunocytes in vitro. 1970 23


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