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)

To clarify the role of vitamin E (alpha-tocopherol) for the induction of cyclooxygenase-2 (COX-2) in rat macrophages stimulated by lipopolysaccharide (LPS), vitamin E-enriched macrophages were prepared by intraperitoneal injection of vitamin E for 6 days at a rate of 5 mg per day. The production of PGE2 was increased in dose- and time-dependent manners by addition of LPS in both control and vitamin E-enriched peritoneal macrophages. The maximum effect of LPS was observed in 12 h at concentration of 5 micrograms/ml. By analyzing COX-2 mRNA level by Northern blot and COX-2 enzyme mass and phosphotyrosine by Western blot, it was revealed that the increase of PGE2 production reflected the induction of COX-2 expression through activation of tyrosine kinase. Vitamin E failed to inhibit PGE2 production in LPS-stimulated macrophages; however, genistein, a tyrosine kinase inhibitor, completely inhibited the production at 100 microM. These results suggest that vitamin E does not inhibit COX-2 expression via LPS-mediated tyrosine kinase signal transduction pathway.
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PMID:Effect of vitamin E on expression of cyclooxygenase-2 in lipopolysaccharide-stimulated rat macrophages. 895 37

Experimental evidence indicates that the lipid peroxidation of biological membranes is often associated with the development of liver fibrosis. We have studied the effect of neutrophil-derived reactive oxygen species (ROS) on collagen synthesis by human hepatic stellate cells (HSC), the major source of collagen in the liver, in a coculture system. Lipid peroxidation in the cocultures was evaluated in terms of either malondialdehyde (MDA) production or the formation of MDA/4-hydroxynonenal protein adducts. The expression of cellular messenger RNAs (mRNAs) was evaluated by either Northern blotting or RNAse protection assay. Nitric oxide (NO) synthase activity in cells was measured by [3H]citrulline formation from [3H]arginine. In vitro exposure of HSC to ROS resulted in the early induction of lipid peroxidation and was associated with a marked increase (threefold) of procollagen I mRNA expression and synthesis. The addition of antioxidants, such as vitamin E or superoxide dismutase (SOD), impaired this stimulation. The inhibition of neutrophil NO formation by N(G)-monomethyl-L-arginine made the ROS-induced stimulation of procollagen I more evident. The addition of xanthine/xanthine oxidase X/XO, a superoxide anion donor, to HSC cultures strongly increased procollagen I synthesis. This stimulation was hampered by the addition of both SOD and sodium nitroprusside (an NO donor). The contribution of HSC to the production of NO in our coculture system was negligible, because inducible NO synthase (iNOS) mRNA was almost undetectable in these cells, and also because the amount of NO produced by HSC stimulated with tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide (LPS) was 500 times less than that synthesized by neutrophils. In conclusion, these results indicate that neutrophil-derived ROS may contribute to the development of hepatic fibrosis associated with alcoholic hepatitis. NO produced by neutrophils may exert a "protective" antioxidant effect by operating as a scavenger of superoxide anion.
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PMID:Neutrophil-derived superoxide anion induces lipid peroxidation and stimulates collagen synthesis in human hepatic stellate cells: role of nitric oxide. 902 48

To evaluate the role of both oxidation and inflammation in atherosclerosis, we compared LDL oxidizability, in vivo lipid and cholesterol oxidation, and basal and lipopolysaccharide (LPS)-stimulated production of various cytokines in normolipidemic patients with diabetes mellitus (DM: n = 11), cigarettes smokers (n = 14). In addition, the effects of vitamin E (600 I.U./day for 4 weeks) on these parameters were evaluated. Initial LDL oxidation characteristics before and after vitamin E were identical in the 3 groups. Plasma thiobarbituric acid reactive substances were higher in DM and smokers versus controls (0.77 +/- 0.22, 0.74 +/- 0.14 versus 0.62 +/- 0.10 mumol malondialdehyde equivalents/l, respectively; P versus controls < 0.05) and normalized after vitamin E supplementation. Total plasma oxysterols were higher in smokers versus controls (354 +/- 104 versus 265 +/- 66 nmol/l, P < 0.05) and unaffected by vitamin E. The basal and LPS-stimulated levels of interleukin-1 beta and tumour necrosis factor alpha (TNF alpha) and the basal level of interleukin-1-receptor antagonist (IL-1RA) were identical for the 3 groups. LPS-stimulated IL-1RA was higher in DM versus controls (10.7 +/- 2.0 versus 8.1 +/- 1.7 pmol/l, P < 0.05). After vitamin E, TNF alpha dropped in controls and smokers, and IL-1RA in smokers only. Results suggest increased in vivo oxidative stress and inflammation in DM and smoking, which is partly overcome by vitamin E.
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PMID:Plasma levels of lipid and cholesterol oxidation products and cytokines in diabetes mellitus and cigarette smoking: effects of vitamin E treatment. 910 58

Starting from the concept that lipopolysaccharide (LPS)-associated hepatotoxicity involves the action of reactive oxygen species, the present study was conducted to test whether vitamin E, a lipophilic antioxidant, prevents LPS-induced hepatic microvascular dysfunction and liver injury. Fifty-two rats were divided into three groups and fed diets containing 0 (n = 16), 75 (n = 18) or 8000 mg (n = 18) alpha-tocopherol acetate/kg food for four weeks. At 1 h and 6 h after intravenous LPS-exposure (10 mg/kg E. coli LPS) hepatic microvascular response and liver injury were assessed by the analysis of Kupffer cell phagocytic activity, leukocyte-endothelial cell interaction and nutritive sinusoidal perfusion (intravital fluorescence epi- illumination technique) as well as bile flow, serum liver enzyme activities and tissue histomorphology. In animals fed with 75 mg vitamin E/kg (standard diet), LPS caused hepatic Kupffer cell activation (increased phagocytic activity) and hepatic microvascular leukocyte activation, with stasis in sinusoids and adherence in postsinusoidal venules (1 h) followed by leukocytic infiltration into tissue (6 h) and progredient sinusoidal perfusion failure (6 h). Hepatic microvascular injury was accompanied by reduced bile flow and enhanced liver enzyme release. Vitamin E-enriched diet (8000 mg/kg) and even vitamin E-deficient diet did not significantly affect LPS-induced hepatic microvascular cell activation and perfusion failure. Thus, we conclude, that vitamin E is not effective to protect from endotoxin-induced hepatic microvascular dysfunction.
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PMID:Dietary vitamin E does not protect from endotoxin-induced hepatic microvascular dysfunction. 913 22

Alzheimer's disease is characterized by the development of a degenerative condition in the elderly, associated with dementia. Upon pathological examination, cerebral amyloid plaques are found which contain denatured protein or peptide material. The process of denaturation of protein requires the presence of excessive heat, organic solvents, or oxidizing acids (OA). It seems that only OA could produce these effects since the other two are not present in the disease. Macrophages can produce the anion of an oxidizing acid known as peroxynitrite (OONO). This material is formed from two free radical gases, namely superoxide anion [.O2]- and nitric oxide (.N = O). Although (OONO)- is very reactive (1000 times more oxidizing than hydrogen peroxide), its half life in solution is only 1 to 2 seconds. Therefore, when it oxidizes a substance (such as protein) peroxynitrite disappears. The brain contains cells called microglia which are produced from monocytes in the same way as other types of macrophages from the lung and liver etc. The macrophages from the lung (alveolar) and liver (Kupfer cells) produce large amounts of peroxynitrite when activated by particles (silica) or infectious agents (lipopolysaccharide or interferon). Microglia produce highly oxidizing substances as well, but no one has ever measured production of peroxynitrite from these cells. Assuming that microglia produce peroxynitrite, or other similar oxidants, anti-oxidant and anti-inflammatory drugs should be helpful in treatment of early forms of the disease. In addition, large doses of anti-oxidant vitamin C and vitamin E might be helpful to people with Alzheimer's disease.
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PMID:The possible role of peroxynitrite in Alzheimer's disease: a simple hypothesis that could be tested more thoroughly. 918 21

Injection of guinea pigs with a single dose of Escherichia coli lipopolysaccharide (3.2 mg/100 g) induces a reversible endotoxic shock that was evaluated by measuring plasma glucose levels and aspartate aminotransferase activity at 24 h after lipopolysaccharide injection. The hypoglycaemia and the increase in plasma aminotransferase activity observed, correlated with the alterations found during the recovery phase of endotoxic shock. When lipid peroxidation and some antioxidant systems were measured in lungs from treated animals, we only found differences in ascorbic acid content, that was decreased by 50%. Lipopolysaccharide treatment results in a depression of pulmonary phosphatidylcholine synthesis, that correlates with the surfactant deficiencies associated with respiratory illnesses in septic shock. Guinea pigs fed on a diet with a low content in ascorbic acid were more sensitive to endotoxin. In these animals we found no detectable levels of ascorbic acid in lung, whereas both vitamin E lung levels and pulmonary phosphatidylcholine synthesis were significantly decreased. Our results point out the significance of ascorbic acid in the protection against oxidative lung injury associated to endotoxaemia, and validate our shock model for further studies on the mechanisms of this pathological condition.
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PMID:Impaired phosphatidylcholine biosynthesis and ascorbic acid depletion in lung during lipopolysaccharide-induced endotoxaemia in guinea pigs. 935 41

The production of Prostaglandin E2 (PGE2) and Thromboxane B2 (TXB2) by turkey blood monocytes and a chicken mononuclear phagocytic cell line MQ-NCSU after exposure to vitamin E (VE) was examined. Turkey embryos were exposed in ovo to 0 and 10 international units (IU) of VE; blood monocytes were collected at 2 weeks of age and cultured. MQ-NCSU macrophage monolayers were exposed to 0, 0.1, 0.25, and 0.5 IU VE. The monocyte/macrophage cultures were exposed to 1 microgram/mL bacterial lipopolysaccharide (LPS). Non-stimulated parallel cultures were maintained as controls. The PGE2 and TXB2 levels were quantitated in culture supernatants by a competitive ELISA. Blood monocytes from the 10 IU VE poults produced lower PGE2 levels as compared with the 0 IU VE controls. Upon stimulation with LPS, monocytes from the 10 IU VE group exhibited levels of PGE2 that were higher than the 0 IU VE group. Levels of TXB2 were not quantitated in the poult blood monocyte culture supernatants. The PGE2 and TXB2 levels in the supernatant of the VE treated MQ-NCSU macrophage cultures were lower than the 0 IU VE controls. Stimulation with LPS resulted in increased PGE2 and TXB2 production by the VE-exposed macrophages. The results from this study suggest that in ovo or in vitro exposure with VE may either upregulate or downregulate PGE2 and TXB2 production by monocytes/macrophages, and that this production may be dependent upon the exposure to a variety of external stimuli and/or the state of macrophage activation.
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PMID:Vitamin E exposure modulates prostaglandin and thromboxane production by avian cells of the mononuclear phagocytic system. 943 47

The role of vitamin E in cell regulation in addition to its function as an antioxidant has attracted attention. The effects of alpha-tocopherol (T) and alpha-tocopheryl succinate (TS) on transcriptional activation of the tumor necrosis factor alpha (TNF-alpha) gene and nuclear factor kappa B (NF-kappa B) activation were examined. Two stable transformants were used: TR-1 cells derived from THP-1 cells transfected with a vector contains the human TNF-alpha promoter (1.4-kb) joined to the human placental alkaline phosphatase (PLAP) coding sequence, and B164 cells derived from the same cell line but carrying the vector containing the human beta-actin promoter (4.3-kb) as a control. The transfectants were cultured in the presence of TS, followed by stimulation with lipopolysaccharide (LPS). After stimulation, PLAP activity secreted into the culture medium was measured. TS reduced TNF-alpha transcriptional activity in a concentration-dependent manner, while no effect was observed on that of the beta-actin promoter. Gel shift assay revealed that THP-1 cells pretreated with TS and then with LPS showed inhibition of NF-kappa B activity by 43% at 50 microM versus the TS-untreated group. Since TS did not affect activator protein-1 (AP-1) activity under the same conditions, the inhibitory effect of TS on NF-kappa B activation might be specific. However, T had no effect on the results of the gel shift assay. Vitamin E transportation was analyzed by simultaneous determination of vitamin E and its derivatives using HPLC. The vitamin E recovered from culture pellets showed almost the same amounts of T and TS transferred and was recovered in unchanged form. These observations indicated that TS inhibited NF-kappa B activation and/or translocation to the nuclei in its unchanged form under the culture conditions used here. These results suggested that vitamin E is involved in signal transduction via an effect distinct from its antioxidant function. To explain the lack of activity with T, it remains to be clarified whether physiological incorporation of T occurred.
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PMID:Inhibition of NF-kappa B transcriptional activity by alpha-tocopheryl succinate. 952 25

Macrophage migration inhibitory factor (MIF) was identified in rat peritoneal macrophages by Western blot analysis and its secretion into culture medium by enzyme-linked immunosorbent assay. We investigated the effect of vitamin E on MIF production in macrophages in response to phorbol 12-myristate-13-acetate (PMA), calcium ionophore A23187, and lipopolysaccharide (LPS). Intraperitoneal injections of vitamin E (5 mg per rat) for 6 successive days resulted in a significant increase of alpha-tocopherol content in peritoneal macrophages (478.3+/-90.7 ng/106 cells) compared with the control (1.5+/-0.5 ng/10(6) cells). For the control macrophages, MIF content of the medium (2.5x10(6) cells/18 ml) without stimulation was 2.27+/-0.20 ng/ml after 14 h culture, whereas stimulation with calcium ionophore A23187 (400 nM) and LPS (5.0 microg/ml) induced the elevation of MIF content to 3. 66+/-0.41 and 4.12+/-0.58 ng/ml, respectively. On the other hand, vitamin E-enriched macrophages without stimulation showed less MIF content (0.77+/-0.23 ng/ml) than the control. Similarly, the increase of MIF of vitamin E-treated macrophages was significantly suppressed after stimulation with calcium ionophore A23187 or LPS, compared with the control macrophages. From analysis of intracellular MIF content by Western blot, we found no alteration of intracellular MIF content of vitamin E-macrophages, in contrast to the decreased content of control stimulated-macrophages. Taken together, these results indicate that vitamin E may contribute to the regulation of immune responses through regulation of MIF secretion.
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PMID:Inhibition of macrophage migration inhibitory factor secretion from macrophages by vitamin E. 973 71

Aminoglycosides, widely used because of their large-spectrum antibiotic effects, should not interfere with the healing process of an ulcer or an infected wound. We evaluated the effects of amikacin or the excipients present in the topic formulation BG 90, powder 2. 5% (Boniscontro e Gazzone S.r.l., Rome, Italy), on human monocyte chemotaxis and the release of profibrotic factors by resting or lipopolysaccharide (LPS)-activated monocytes. The chemotactic response of monocytes to zymosan-activated serum is not modified in vitro by pre-incubation of the cells with amikacin (2 and 10 microg/ml/10(6) cells) or excipients. Unstimulated monocytes did not secrete appreciable amounts of cytokines. Vice versa, amikacin-stimulated cells released platelet-derived growth factor AB (PDGF-AB) (about 340 pg/ml), transforming growth factor (TGF)-beta1 (about 10 pg/ml), and tumour necrosis factor (TNF)-alpha (over 1,100 pg/ml); among excipients, ZnO and vitamin E induced PDGF-AB release (about 320 and, respectively, 200 pg/ml), while stimulation of monocyte monolayers by the other excipients did not lead to appreciable cytokine release. As expected, LPS-activated human monocytes produced PDGF-AB, TGF-beta1, and TNF-alpha. When monocytes were co-stimulated with LPS and amikacin, the PDGF-AB and TGF-beta1 values almost overlapped with those from the stimulation of cells with LPS alone, while TNF-alpha production was slowly reduced. The results show a stimulating effect of aminoglycoside on the production of profibrotic factors and, therefore, on the healing process of wounds in addition to a modulating effect on the production of pro-inflammatory cytokines like TNF-alpha. Moreover, ZnO and tocopherol (free-radical scavengers), used as excipients in the topic formulation, induce the release of growth factors with profibrotic activity (PDGF-AB). Further research is warranted to explore the effects of this formulation in vivo, verifying whether the association of the antibiotic with scavengers has a double advantage in topical amikacin: on the one hand, it could limit the damage from free radicals, and on the other it could favour tissue healing.
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PMID:Effects of a new topic amikacin formulation on chemotaxis and release of profibrotic factors by human monocytes. 975 99


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