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)

Vitamin E, a lipophilic antioxidant, has effectively inhibited the activation of cytokine-induced nuclear factor kB (NFkB). Since NFkB plays a critical role in the induction of an isoform of nitric oxide synthase (iNOS) gene by lipopolysaccharide (LPS), we investigated the effect of a vitamin E derivative, pentamethyl-hydroxychromane (PMC), which is an extremely potent inhibitor of NFkB activation, on the induction of nitric oxide (NO) synthesis and iNOS mRNA by LPS. PMC inhibited the LPS-stimulated induction of NO production in a concentration-dependent fashion in cultured J774 macrophages and rat vascular smooth muscle cells without evidence of cytotoxicity. However, the addition of PMC to J774 macrophages after the induction of iNOS did not inhibit NO production. Treatment of J774 macrophages with LPS resulted in a significant expression of iNOS mRNA, which was profoundly reduced by PMC. Data suggest that PMC inhibits the induction of iNOS by preventing iNOS gene expression through inhibition of NFkB activation.
 ...
PMID:Pentamethyl-hydroxychromane, vitamin E derivative, inhibits induction of nitric oxide synthase by bacterial lipopolysaccharide. 753 70

A potential role for lipoxygenase (LO) products and reactive oxygen species (ROS) in mouse B-lymphocyte activation and differentiation was investigated. Previously published investigations with the nonspecific 5-LO (EC 1.13.11.34) and 12-LO (EC 1.13.11.31) inhibitors such as nordihydroguaiaretic acid (NDGA) and 6,7-dihydroxycoumarin (Esculetin), are misleading in that they suggest lymphocyte LO activity is required for activation and differentiation of these cells. In initial support of this concept, we report that NDGA and Esculetin completely inhibited B-lymphocyte activation mediated by either membrane immunoglobulin (mIg), or the lipopolysaccharide (LPS) receptor. NDGA and Esculetin completely inhibited cell enlargement and proliferation, exhibiting half maximal inhibitory concentrations (IC50S) of approximately 1 x 10(-6) M. In contrast, the highly specific 5-LO inhibitors BAY X 1005, MK-886 and Wy 50,295 did not inhibit cell enlargement or proliferation. Moreover, 5,8,11-eicosatriynoic acid (ETI) which inhibits 5- and 12-LO, and 5, 8, 11, 14-eicosatetraynoic acid (ETYA) which inhibits all known LOs did not affect B-lymphocyte proliferation. Interestingly, NDGA and Esculetin are antioxidants, unlike BAY X 1005, MK-886, Wy 50,295, ETI and ETYA. Our hypothesis was that the antioxidant activities of NDGA and Esculetin were reponsible for inhibiting B-lymphocyte activation and proliferation and we speculated that ROS and not LO activity was required for both processes. Additional antioxidants such as butylated hydroxy toluene, o-phenanthroline, thiourea, and alpha-tocopherol (vitamin E), also inhibited B-lymphocyte proliferation induced by either the LPS or mIg receptors. These agents exhibited IC50S of 1 x 10(-8) M, 5 x 10(-10) M, 6 x 10(-3) M and 5 x 10(-5) M, respectively. When resting B-lymphocytes were treated with a source of ROS (1 x 10(-5) M H2O2), cells enlarged in a temperature-sensitive manner, which is similar to LPS-induced enlargement. Both NDGA and Esculetin completely inhibited H2O2-induced enlargement. These results further indicate that ROS are required for B-lymphocyte activation and proliferation. Similar results were obtained for B-lymphocyte differentiation. NDGA and Esculetin completely inhibited the development of plasma cells and displayed IC50S of 5 x 10(-6) M. Conversely, BAY X 1005, MK-886, Wy 50,295, ETI, and ETYA did not block the formation of plasma cells. Therefore, ROS are also crucial for differentiation into plasma cells. These experiments are the first to directly illustrate that intracellular ROS mediate B-lymphocyte activation, proliferation and differentiation and that LO products are not required for these processes.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Reactive oxygen species and not lipoxygenase products are required for mouse B-lymphocyte activation and differentiation. 792 3

As vitamin E enhances immune responses, it may reduce dietary ethanol (EtOH)-induced immune suppression, thereby favorably affecting host disease resistance. The effects of dietary vitamin E at higher level in alcohol-fed female C57BL/6 mice was determined via in vitro cytokine production by splenocytes and thymocytes, and some other immune functions. A 15-fold increase of vitamin E (160 IU/liter) in a liquid diet (National Council Research), with or without EtOH (4.5%, v/v), was fed to mice for 10 weeks. Vitamin E supplementation restored production of interleukin-2, -5, -6, -10, and interferon-gamma by concanavalin A (Con A)-stimulated splenocytes and interleukin-6 and tumor necrosis factor-alpha by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. However, it had no effect on interleukin-4 secretion, which was also reduced by splenocytes from EtOH-fed mice. Vitamin E supplementation also restored EtOH-suppressed, mitogen-induced splenocyte proliferation, but not thymocyte proliferation, although it slightly increased production of immunoglobulin A and G by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. Dietary vitamin E, furthermore, significantly increased interleukin-2 and -6 secretion by Con A-stimulated thymocytes, which were suppressed by dietary EtOH, although it had no effect on interleukin-4 and interferon-gamma production by Con A-stimulated thymocytes from EtOH-fed mice. These data suggest that dietary vitamin E supplementation can modulate dysregulation of cytokines initiated by dietary EtOH and restore immune dysfunctions induced by EtOH ingestion.
 ...
PMID:Dietary vitamin E modulation of cytokine production by splenocytes and thymocytes from alcohol-fed mice. 804 38

In order to determine the contribution of suppressive factors secreted from macrophages to the age-associated decline in T-cell mediated mitogenic responses, experiments were conducted to characterize eicosanoid and H2O2 production, total cellular fatty acid, and vitamin E composition of splenocytes isolated from young (4 mo) and old (24 mo) C57BL/6NIA mice. An age-related increase was observed in Ca++ ionophore A23187-stimulated ex-vivo production of prostaglandin (PG) E2, leukotriene (LT) B4, and LTC4 (p < .01), and in concanavalin A (ConA)-stimulated PGE2 production (p < .01). No age-related difference was observed in ex-vivo production of 12- and 15-hydroxyeicosatetranoic acid (HETE). The age-related increase in PGE2 production was also observed in lipopolysaccharide-stimulated peritoneal macrophages of C57BL/6NIA mice and ConA and phytohemagglutinin (PHA)-stimulated splenocytes isolated from DBA mice. Inhibition of cyclooxygenase with indomethacin resulted in increased ConA-stimulated proliferation of splenocytes from old mice (p < .01), while 5-lipoxygenase inhibition did not have an effect on mitogen induced proliferation. Furthermore, PGE2 addition to purified splenic T-cells decreased their proliferation. No age-related differences were observed in total cellular fatty acid composition, vitamin E level, or ex-vivo production of H2O2 from splenocytes stimulated with 10 or 100 ng phorbol myristate acetate (PMA). These data indicate that aging is associated with increased production of PG and LT from activated splenocytes. Inhibition of PGE2 but not LT production enhances mitogenic responses of old mice, suggesting a contributory role for PGE2 in the age-associated decline of T-cell responsiveness to polyclonal mitogens.
 ...
PMID:Age differences in eicosanoid production of mouse splenocytes: effects on mitogen-induced T-cell proliferation. 805 32

The effects of supplementing gestation and lactation diets of gilts with different combinations of vitamin E at or above NRC recommended levels (22, 44, or 88 IU/kg during gestation and 55, 110, and 220 IU/kg during lactation) and types of fat (5% added tallow or fish oil or no added fat) on humoral and cellular immunity of gilts and their pigs were evaluated. With only two exceptions, total IgG, IgM, and IgA in colostrum, milk, and plasma of gilts and in plasma of their pigs did not show significant (P > .05) effects, and no interactions between vitamin E and fat supplementation were observed. Cellular immunity was measured as lymphocyte proliferation response to phytohemagglutinin (PHA), concanavalin A (Con A), purified protein derivative of Mycobacterium avium, keyhole limpet hemocyanin, Escherichia coli lipopolysaccharide (LPS), and Salmonella typhimurium LPS. Only the nonspecific mitogens, PHA and Con A, induced proliferation of gilt and pig lymphocytes. Fish oil supplementation in the gilts' diets resulted in lower (P < .01) postpartum PHA response in gilts and slower (P < .05) acquisition of PHA response in newborn pigs compared with groups with added tallow or no added fat. The vitamin E supplementation did not have a significant positive effect on either PHA or Con A response of the gilts. However, the rate of acquisition of PHA response and Con A response in newborn pigs was greater (P < .05) for groups supplemented with 110 and 220 IU/kg of vitamin E than for the group supplemented with 55 IU/kg vitamin E.
 ...
PMID:Effect of supplementing gilts' diets with different levels of vitamin E and different fats on the humoral and cellular immunity of gilts and their progeny. 818 83

Groups of mice were given oestrone acetate or vitamin E subcutaneously to determine how these treatments might modify responses to endotoxic lipopolysaccharide given intraperitoneally. Release of hepatic transaminase and tumour necrosis factor (TNF) into serum and induction of manganous superoxide dismutase in the liver were measured. Significantly less transaminase and TNF were released into the circulation in mice given the steroid or vitamin E before the endotoxin. In endotoxin-treated animals oestrogen administration did not influence induction of the superoxide dismutase. It is postulated that protection of the liver in these experiments arises from a direct pharmacological antioxidant effect of the oestrogen.
 ...
PMID:Protective effect of an oestrogen against endotoxin-induced liver enzyme release. 833 80

Vitamin E was tested as an adjuvant in an Escherichia coli (O111:B4) J5 vaccine. Twenty cows were assigned to five groups of 4 cows. Cows in four groups were vaccinated with an E. coli J5 bacterin containing 5 ml of 10(9) boiled cells/ml. Vaccinations were at drying off, 30 d after drying off, and within 48 h after calving. Vaccine adjuvants differed among groups. The four treatment adjuvants were 5 ml of Freund's incomplete adjuvant, 5 ml of vitamin E, 2.5 ml of Freund's plus 2.5 ml of vitamin E, and 5 ml of PBS. Cows in the fifth group were unimmunized controls. A front mammary quarter of each cow was challenged by infusion of 10 micrograms of E. coli J5 lipopolysaccharide approximately 4 wk into lactation. Vitamin E alone enhanced serum IgM titers but had no effect on milk IgM or serum and milk IgG titers. The mixture of Freund's plus vitamin E resulted in peak IgG titers in serum and milk comparable with that of Freund's alone. Persistency of IgG titers in cows immunized with the Freund's plus vitamin E mixture was greater than the persistency of titers for cows immunized with the vaccine containing Freund's alone as the adjuvant. The mixture of Freund's plus vitamin E had a synergistic effect in reducing severity of systemic clinical signs.
 ...
PMID:Vitamin E as an adjuvant in an Escherichia coli J5 vaccine. 844 93

Studies were performed to investigate the effect of a polyphenol rich extract from black tea and vitamin E on bacterial lipopolysaccharide (endotoxin) induced IL-6 production, alterations in liver glutathione and antioxidant acute phase protein (caeruloplasmin) concentration, in rats fed on a synthetic diet for 21 days. In the vitamin E sufficient group a significantly lower IL-6 concentration than in vitamin E deficient animals was observed. Addition of tea extract to the diet produced a similar reduction in IL-6, but no synergism occurred in the presence of both vitamin E and tea extract. However, a significantly lower caeruloplasmin and a significantly higher liver glutathione concentration was observed in rats fed both substances. It is suggested that consideration of dietary components which alter antioxidant/oxidant status may contribute towards treatment of inflammatory/autoimmune diseases.
 ...
PMID:Endotoxin induced production of interleukin-6 is enhanced by vitamin E deficiency and reduced by black tea extract. 856 28

Plasma corticosterone (CS) and brain free aminoacids were determined in male rats 2 hr after acute exposure to bacterial endotoxin stress BES (2.0 mg/kg i.p. of lipopolysaccharide, LPS). A significant increase in the levels of plasma CS and brain taurine (Tau), aspartate (As), glutamate (Glu), glycine (Gly) and valine (Val) was observed following BES. When vitamin E (alpha-tocopherol acetate AT) was given orally (0.25 gm/kg/day) 4 days before induction of BES, the plasma CS as well as the brain Glu levels were significantly reduced to the control values. These results indicate that plasma CS and brain Glu may be involved in the mechanisms by which AT protects against the neurotoxicity of BES.
 ...
PMID:Vitamin E protects against bacterial endotoxin-induced increase of plasma corticosterone and brain glutamate in the rat. 873 31

The effect of supplementation with vitamins C and E on cytokine production of healthy adult volunteers was studied in a single-blind trial. Ten subjects in each group received daily vitamin C (1 g ascorbic acid), vitamin E (400 mg dl-alpha-tocopheryl acetate), or vitamins C and E for 28 d. Plasma concentrations of alpha-tocopherol, ascorbate, and lipid peroxides as well as the production of cytokines by peripheral blood mononuclear cells (PBMCs) were measured before, during, and at the end of the supplementation and 1 wk later. PBMCs were cultured in the presence of absence of lipopolysaccharide for 24 h. The interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) in the culture supernates were assayed by enzyme-linked immunosorbent assay methods. Production of IL-1 beta and TNF-alpha in the group supplemented with vitamins C and E was significantly higher (P < 0.05) than that of the groups given vitamin E or vitamin C alone. The enhancing effect of supplementation with a combination of vitamins E and C coincided with peak plasma alpha-tocopherol and ascorbate concentrations and the lowest plasma lipid peroxide concentrations (P < 0.05) on day 14. In addition, an in vitro experiment with PBMCs showed that vitamins E and C reduced lipopolysaccharide-induced prostaglandin E2 production and enhanced TNF-alpha production. These results indicate that combined supplementation with vitamins C and E is more immunopotentiating than supplementation with either vitamin alone in healthy adults.
 ...
PMID:Supplementation with vitamins C and E enhances cytokine production by peripheral blood mononuclear cells in healthy adults. 917 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>