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LPS Treatment (lp + treatment)
Selected AbstractsInfluence of different phosphorus levels and phytase supplementation in gestation diets on sow performanceJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 7-8 2007K. Lyberg Summary A total of 104 sows of different parities were studied. They were fed four diets with different phosphorus (P) levels during gestation for two reproductive cycles, while the same diet was fed during lactation. The aim was to decrease the total P level in the diet during gestation and to evaluate the effect on sow performance. The gestation treatments were low P (LP,; 3.7 g P/kg feed), low P with phytase (LP+, Ronozyme® P; 765 FTU/kg feed), medium P (MP; 4.5 g P/kg feed) and high P (HP; 6.0 g P/kg feed). Daily feed allowances were 2.6 kg during gestation and 9.2 kg during lactation. Number of born piglets and piglet mortality were higher (p < 0.05) in the LP treatments than in the MP and HP treatments. No difference (p > 0.05) in the numbers of live-born piglets, piglet birthweights, sow weights or piglet weight gains was found between the treatments. Phosphorus level in sow milk was the highest (p < 0.05) in the MP treatment, while no effects (p > 0.05) of treatment were found on milk Ca levels, P and Ca levels in serum of sows and piglets, nor on the analysed mineral, fat and protein contents of piglets. The estimated average requirement of P for the entire gestation period was 4.4,4.5 g/day. In conclusion, a reduction of dietary total P content during gestation did not result in negative effects on sow or piglet performance. This suggests that it should be possible to lower the dietary P content for gestating sows, compared with earlier recommendations, and thereby reduce the environmental P pollution. [source] The zinc finger protein Gfi1 acts upstream of TNF to attenuate endotoxin-mediated inflammatory responses in the lungEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2006Jianmin Jin Abstract Gfi1 is a 55-kD nuclear zinc finger protein that is differentially expressed in lymphoid and myeloid cells. Gfi1,/, mice show a very strong systemic response to the endotoxin LPS and die rapidly within 36,h with symptoms of septic shock. Here we report that the pathohysiological processes for this exaggerated inflammatory response take place in the lung. After LPS treatment, lungs of Gfi1,/, mice showed a rapid accumulation of mononuclear cells and a significant overproduction of inflammatory cytokines such as TNF, IL-1, and IL-6. Increased cytokine production was also observed in blood-free perfused lungs from Gfi1,/, mice exposed to either LPS or overventilation. Alveolar macrophages but not airway epithelial cells from Gfi1,/, mice were found to be responsible for the enhanced cytokine production. Strikingly, when the TNF gene was deleted, Gfi1,/, animals were completely rescued from LPS hypersensitivity and had significantly lower IL-1, and IL-6 levels. We conclude that the unrestrained endotoxin response of Gfi1,/, mice occurs mainly in the lung and that Gfi1 represents a novel factor limiting the inflammatory immune response of this organ, and propose that Gfi1 exerts its regulatory function in alveolar macrophages downstream of the LPS receptor (TLR4) and upstream of TNF. [source] Enhancement by pyrazole of lipopolysaccharide-induced liver injury in mice: Role of cytochrome P450 2E1 and 2A5,HEPATOLOGY, Issue 1 2006Yongke Lu The mechanisms by which alcohol causes liver injury are still not certain. Either LPS or CYP2E1 are considered independent risk factors involved in alcoholic liver disease, but mutual relationships or interactions between them are unknown. In the present study, the possible synergistic action of CYP2E1 and LPS in liver injury was investigated by evaluating the effects of pyrazole (inducer of CYP2E1), Chlormethiazole (CMZ), an inhibitor of CYP2E1, and CYP2E1-knockout mice. Mice were injected with pyrazole (150 mg/kg, ip) daily for 2 days, followed by LPS injection (4 mg/kg, ip). CMZ (50mg/kg, ip) was administered 15 h before and 30 min after LPS treatment, respectively. LPS-induced liver injury was enhanced by pyrazole, as indicated by pathological changes and increases in ALT and AST, and positive TUNEL staining. LPS-induced oxidative stress was also enhanced by pyrazole as indicated by increases in 4-hydroxy-2-nonenal and 3-nitrotyrosine adduct formation. CMZ protected against the pyrazole enhanced LPS liver injury and oxidative stress. CYP2E1 but also CYP2A5 were increased by the pyrazole/LPS treatment. CMZ decreased the elevated CYP2E1 activity by 90%, but CYP2A5 activity was also lowered (30%-50%). CYP2E1-knockout mice exhibited only minor liver injury after treatment with pyrazole/LPS, but wild-type mice exhibited severe liver injury. While no CYP2E1 was present in the CYP2E1 knockout mice, CYP2A5 activity was also lower. In conclusion, induction of CYP2E1 plays an important role in the enhancement of LPS liver injury by pyrazole, but some contribution by CYP2A5 cannot be excluded. (HEPATOLOGY 2006;44:263,274.) [source] Downregulation of inducible nitric oxide synthetase by neurotrophin-3 in microgliaJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2003Shun-Fen Tzeng Abstract Microglia activated after many neurological degeneration of the central nervous system (CNS) act as important regulators for neuropathogenesis in the injured CNS via producing proinflammatory mediators, such as nitric oxide (NO), TNF-,, and IL-1,. Neurotrophin-3 (NT-3) is a well-known trophic factor for neural survival, development, and plasticity. Activated microglia are NT-3-producing cells in the injured CNS, and express its receptor-TrkC. However, little is known about the effect of NT-3 on activated microglia. In this study, pre-treatment of a mouse microglial cell line, BV2, with NT-3 for 24 h indicated that NT-3 reduced the inducible form of NO synthase (iNOS), NO, and TNF-, in BV2 stimulated with lipopolysaccharide (LPS). NT-3 exerted less effect on the reduction of these proinflammatory mediators when it was added to BV2 cultures either simultaneously with LPS or post LPS treatment. These findings indicate that NT-3 may serve as an anti-inflammatory factor to suppress microglial activation. J. Cell. Biochem. 90: 227,233, 2003. © 2003 Wiley-Liss, Inc. [source] Effect of Yam (Dioscorea alata Compared to Dioscorea japonica) on Gastrointestinal Function and Antioxidant Activity in MiceJOURNAL OF FOOD SCIENCE, Issue 7 2006Cheng-Chin Hsu ABSTRACT:, Effects of Chinese yam (Dioscorea alata) and Japanese yam (Dioscorea japonica) on gastrointestinal functions including intestinal microflora and intestinal enzymes' activities, as well as antioxidant protection against lipopolysaccharide (LPS)-induced oxidative damage, in Balb/cA mice were examined. In part I, mice were fed yam-supplemented diet for 4 or 8 wk, and killed with carbon dioxide. In part II, mice were fed yam-supplemented diet for 4 wk, and followed by intraperitoneal LPS treatment (i.p. 4 mg/kg bodyweight). The intake of Chinese yam and Japanese yam significantly changed intestinal microflora, in which the colony numbers of Bifidobacterium and Lactobacillus were increased and the colony numbers of Clostridium perfringens were decreased (P < 0.05). The intake of both Chinese and Japanese yams also significantly elevated the activity of leucine aminopeptidase and lipase (P < 0.05), and the activities of sucrase and maltase were increased only in 20% yam-treated groups (P < 0.05). The preintake of yam significantly alleviated subsequent LPS-induced oxidative injury by decreasing lipid oxidation level and fibronectin production and elevating superoxide dismutase activity (P < 0.05). Both Chinese and Japanese yams contained dietary fibers, polyphenols, and flavonoids, which may contribute to the observed gastrointestinal function and antioxidant protection. These results suggest that both Chinese yam and Japanese yam were beneficial for intestinal health and oxidation prevention. [source] Effects of lipopolysaccharide on platelet-derived growth factor isoform and receptor expression in cultured rat common bile duct fibroblasts and cholangiocytesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2009Tae-Hyeon Kim Abstract Background and Aim:, Little is known about the role of platelet-derived growth factor (PDGF) in biliary fibrosis in the setting of bacterial colonization of the biliary tree. We therefore sought to investigate whether exposure to bacterial lipopolysaccharide (LPS) alters PDGF isoform and receptor expression in cultured rat common bile duct fibroblasts (CBDF) and normal rat cholangiocytes (NRC). Methods:, Collagen content in cells and media was assessed by colorimetric assay and gel electrophoresis. mRNA levels of PDGF-A and -B, and PDGF-Receptors (PDGF-R) , and , were measured by relative quantitative real-time PCR. Protein levels of PDGF-AA, AB and BB were measured by ELISA, and PDGF-R, and PDGF-R, by Western blot. Results:, In CBDF, LPS increased total soluble collagen synthesis and secretion. PDGF-R, and , mRNA and protein were also increased by LPS treatment in CBDF. Lipopolysaccharide treatment elicited an increase in PDGF-A and -B mRNA levels in CBDF. In NRC, levels of PDGF-A mRNA increased in a dose-dependent fashion following LPS treatment, whereas PDGF-B mRNA showed no response. PDGF-AA secretion was higher by CBDF than by NRC. PDGF-BB levels were also higher in CBDF than in NRC. While PDGF-BB levels did not respond to LPS treatment in CBDF, there was a dose-dependent response of this isoform to LPS in NRC. Intracellular and secreted PDGF-AB increased with LPS treatment in NRC. Conclusions:, These results support a model in which chronic bacterial colonization of the biliary tree induces fibrosis through PDGF-dependent mechanisms. [source] Anti-inflammatory effect of retinoic acid on prostaglandin synthesis in cultured cortical astrocytesJOURNAL OF NEUROCHEMISTRY, Issue 1 2008Eric Kampmann Abstract Prostanoids are important mediators of inflammation and pain signaling. Although it is now well accepted that astrocytes participate in inflammatory reactions in the CNS, the molecular regulation of this activity is still largely unknown. Specifically, the regulation of prostanoid synthesis by this type of glia remains to be resolved. Recent evidence suggests that the transcriptional regulator retinoic acid (RA) is involved in regulation of the immune response. We have investigated the expression pattern of the enzymes that catalyze prostanoid and leukotriene synthesis in cultured cortical astrocytes, their stimulation by lipopolysaccharides (LPS) and their regulation by RA. The data indicate that astrocytes are an important source of prostaglandins (PGs) and that RA reduces their inflammatory biosynthesis. LPS treatment induced the expression of enzymes for the production of arachidonic acid and PGs but caused down-regulation of a PG degrading enzyme and of leukotriene synthesizing enzymes that compete with PG synthesis. Consequently, the secretion of the PGE2 was highly increased after LPS exposure. RA counteracted the inflammatory regulation of cyclooxygenase (COX)-2 mRNA and protein in astrocytes and thereby reduced the synthesis of PGE2 by approximately 60%. In the absence of LPS, RA enhanced the expression of COX-1 mRNA. In conclusion, RA might be effective in suppressing inflammatory processes in the brain by inhibiting PG synthesis. [source] Differential expression of heme oxygenase isoforms in rat brain by endotoxin (LPS)JOURNAL OF NEUROCHEMISTRY, Issue 2003V. Calabrese Heme oxygenase-1 (HO-1) is a stress protein expressed in various pathological conditions associated with oxidative stress. Brain HO-1 expression and activity in response to LPS treatment showed regional variability with the highest levels in the substantia nigra (SN) and hippocampus. HO-1 induction by LPS was redox-sensitive and associated with increased levels of NO synthase and arginase, two proteins involved in the regulation of cellular redox state. Brain HO-2 and HO-3 expression, studied by quantitative RT-PCR, did not show significant changes. Our data suggest an interaction between NO and the HO system in the brain after LPS treatment. As SN and hippocampus are involved in Parkinson's and Alzheimer's diseases, understanding interaction of these proteins in the brain will help to elucidate the mechanisms involved in neurodegeneration. [source] NF,B Activation in Mouse Pituitary: Comparison of Response to Interleukin-1, and LipopolysaccharideJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2003P. Parnet Abstract The mouse anterior pituitary contains both types of interleukin (IL)-1 receptors, IL-1 receptor type I (IL-1RI) and IL-1 receptor type II (IL-1RII). These receptors are expressed mainly on somatotroph cells. In the present study, the ability of the mouse pituitary to respond in vivo to IL-1 or to lipopolysaccharide (LPS) was demonstrated by measuring, with an electrophoretic mobility shift assay, the presence of an active NF,B complex in cell nuclei from pituitaries of mice injected intraperitoneally with recombinant rat-IL-1, or LPS. Using immunohistochemistry with an antibody directed against the p65 NF,B subunit, a rapid and transient NF,B response to LPS was observed. This response was present predominantly in the nuclei of glial fibrillary acidic protein (GFAP)-positive cells and F4/80-labelled cells of the posterior and the anterior pituitary 15 min after stimulation and became faint after 2 h. In comparison, the early and strong NF,B response to IL-1, treatment was localized into somatotroph cells, GFAP positive cells and F4/80-labelled cells of the posterior and anterior pituitary. Activation of NF,B in response to IL-1, was no longer apparent in IL-1RI knockout mice, confirming that this receptor is essential for the transduction of IL-1 signal in the pituitary, but remained after LPS treatment. In addition, we investigated the effect of IL-1 on target genes by measuring the mRNA and proteins synthesis of growth hormone (GH), IL-6 and IL-1ra in the pituitary and the plasma. IL-1, was shown to induce a rapid and strong synthesis of IL-6 and IL-1ra in the pituitary but failed to regulate GH contents or release. These data suggest that the pituitary is able to respond to a systemic infection via cytokine-mediated responses transduced by IL-1. [source] 24S-hydroxycholesterol in relation to disease manifestations of acute experimental autoimmune encephalomyelitisJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2007C.E. Teunissen Abstract Levels of the brain-specific cholesterol metabolite 24S-hydroxycholesterol are proposed as possible biomarkers for multiple sclerosis (MS). It is not yet clear for which aspect of the MS disease manifestations 24S-hydroxycholesterol is a reflection. We studied the relation of serum levels of 24S-hydroxycholesterol and other sterols to the disease characteristics of acute experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Serum was analyzed for cholesterol precursors, oxysterols, and plant sterols during the course of disease development. Significantly increased levels of the cholesterol metabolites 24S-hydroxycholesterol and 27-hydroxycholesterol were observed on day 9, before the onset of clinical signs. The serum levels of these oxysterols gradually increased up to 193% and 415%, respectively, at day 17, when clinical symptoms had recovered. Total cholesterol levels were slightly but significantly decreased on day 9 and day 17 in treated animals. Serum levels of cholesterol precursors and plant sterols decreased gradually from day 11 and day 14, respectively. Immunostaining of the 24S-hydroxycholesterol-forming enzyme Cyp46 was shown in macrophage infiltrates. In vitro experiments confirmed the presence of Cyp46 in macrophages and showed a decreased expression after LPS treatment. The data indicate that changes in serum oxysterols occur early in EAE and can be formed by macrophages. These early changes indicate an important role for oxysterols in the development of EAE. © 2007 Wiley-Liss, Inc. [source] Influence of progesterone on myometrial contractility in pregnant mice treated with lipopolysaccharideJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2007Hiroshi Anbe Abstract Aim:, To evaluate the effect of progesterone on interleukin (IL)-6, prostaglandin (PG) E2 and nitric oxide (NO) metabolite (NOx) production and contractile activity by NO in pregnant mice treated with lipopolysaccharide (LPS). Methods:, Pregnant C57BL mice on day 14 of gestation were killed 6 h after i.p. injection of LPS (400 ,g/kg) or vehicle. Progesterone (2 mg) was subcutaneously injected 2 h before LPS treatment. Uterine rings were equilibrated in Krebs-Henseleit solution (37°C) bubbled with 20% O2 and 5% CO2 (pH 7.4) for sampling and isometric tension recording. IL-6, PGE2 and NOx productions were measured from the bathing solution. Changes in spontaneous contractile activity in response to cumulative concentrations of l -arginine, diethylamine/nitric oxide (DEA/NO, the NO donor), and 8-bromo-cGMP (8-br-cGMP) were compared. Integral contractile activity over 10 min after each concentration was calculated and expressed as percentage change from basal activity. Statistical analyses were performed using one-way anova followed by Dunnett's test (significance was defined as P < 0.05). Results:, Interleukin-6 (34.7 ± 6.0 pg/g tissue), PGE2 (66.8 ± 6.7 pg/g tissue) and NOx (51.0 ± 5.4 pmol/2 mL/g wet tissue) production were significantly stimulated by LPS treatment (138.2 ± 23.2, 147.0 ± 29.0, 98.6 ± 16.2, respectively; P < 0.05). l -arginine, DEA/NO and 8-br-cGMP concentration-dependently inhibited spontaneous contractions in uterine rings both in LPS-treated and -untreated animals. Treatment with LPS significantly attenuated the maximal inhibition induced by l -arginine, DEA/NO and 8-br-cGMP in uterine rings from pregnant mice. Progesterone significantly decreased the levels of IL-6 production (74.9 ± 12.1, P < 0.05), but not PGE2 and NOx production, and contractile responses by l -arginine, DEA/NO and 8-br-cGMP. Conclusions:, The administration of LPS is associated with increases in IL-6, PGE2 and NO, and these increases may or may not have a role to play in LPS-induced preterm labor. Progesterone reduced the LPS-induced increase in IL-6 production and this may be one of the ways that progesterone reduces the risk of preterm labor. [source] Apoptosis and Dysregulated Ceramide Metabolism in a Murine Model of Alcohol-Enhanced Lipopolysaccharide HepatotoxicityALCOHOLISM, Issue 10 2000Ion V. Deaciuc Background: The role of apoptosis in EtOH-induced liver injury has not been investigated much. Therefore, the question whether apoptosis is a contributory factor to alcoholic liver disease remains to be answered. The purpose of this study was to characterize the liver apoptotic response in a murine model of alcohol-enhanced lipopolysaccharide (LPS) hepatotoxicity. Methods: Mice were fed an alcohol-containing liquid diet for 49 days followed by an acute LPS challenge. The liver state was judged on the basis of histological appearance, plasma liver enzyme activity (alanine:2-oxoglutarate and aspartate:2-oxoglutarate aminotransferases, as markers of hepatocytolysis), and plasma hyaluronan levels (as a marker of the sinusoidal endothelial cell scavenging function). The liver apoptotic response was assessed by DNA fragmentation (TUNEL procedure), and caspases-3 and -8 activity. To determine if ceramide played a role in the liver apoptotic response, the activity of acidic sphingomyelinase and tissue content of ceramide were also quantified. Results: Alcohol exposure induced fat accumulation and sensitized the liver to LPS injurious effects. Plasma liver enzyme activity was elevated by alcohol and this effect was potentiated by LPS. Liver apoptosis was augmented by both alcohol and LPS treatment as reflected by high frequency of positive TUNEL staining nuclei and by an increased activity of caspase-3 and -8. Acidic sphingomyelinase activity was also increased and it was associated with an elevated tissue content of ceramide. In addition, LPS also increased plasma TNF- , levels. These changes were accompanied by elevated plasma hyaluronan, reflecting an impaired sinusoidal endothelial cell scavenging function. Conclusions: These results provide a more complete description of the liver apoptotic response to both alcohol and LPS and may constitute the basis for further mechanistic studies on a possible role apoptosis may play in alcoholic liver injury. [source] Inflammatory change of fatty liver induced by intraportal low-dose lipopolysaccharide infusion deteriorates pancreatic insulin secretion in fructose-induced insulin-resistant ratsLIVER INTERNATIONAL, Issue 8 2008Po-Shiuan Hsieh Abstract Background: This study tested whether subacute inflammatory change of fatty liver induced by portal endotoxaemia is detrimental to pancreatic insulin secretion in fructose-fed rats (FFRs) with fatty liver. Methods: Rats were randomly assigned into two groups with a regular or fructose-enriched diet for 8 weeks. Rats, after fructose feeding for 4 weeks, were further divided into three subgroups: on fructose diet alone, on fructose diet combined with intraportal saline or lipopolysaccharide (LPS) infusion (n=8 per group) for the next 4 weeks. In another set of experiments, the liver and pancreatic tissues were obtained for histological examination in these four groups. Pancreatic insulin secretion was evaluated by in vivo hyperglycaemic clamp study. Results: Fasting plasma insulin concentrations and homoeostasis model assessment-insulin resistance, an insulin resistance score, were significantly increased in FFRs but failed to change in rats with LPS treatment. The 4-week intraportal LPS infusion significantly increased circulating aspartate transaminase, alanine transaminase and C-reactive protein levels but did not alter endotoxin levels in FFRs. The increased white blood cell count was also noted in rats after intraportal LPS infusion for 2 and 4 weeks. The attenuated first-phase and second-phase insulin responses in FFRs shown in hyperglycaemic clamp were further deteriorated in those with intraportal LPS infusion. Increased histopathological scores of liver and pancreas shown in FFRs were further increased in those combined with portal endotoxaemia. Conclusion: This study demonstrates that the chronic subacute inflammatory change of fatty liver induced by mild portal endotoxaemia could deteriorate insulin secretion in a rodent model of metabolic syndrome and fatty liver. [source] Alterations in Syncytiotrophoblast Cytokine Expression Following Treatment with LipopolysaccharideAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2006Yuehong Ma Problem, The placental syncytium is a differentiated cell type on the surface of the villus that has the potential to release cytokines directly to maternal blood. Responsiveness of this cell type to inflammatory compounds remains largely unelucidated. Method of study, Response to a pro-inflammatory (lipopolysaccharide, LPS) and an anti-inflammatory (dexamethasone, DEX) compound was studied in primary cultures of syncytiotrophoblasts (SCTs). Cells were incubated with and without LPS and DEX. Cytokine levels in conditioned media were determined by enzyme-linked immunosorbent assay and proteome arrays. Results, LPS treatment induced a fourfold increase in interleukin-8 (IL-8) levels in SCTs. LPS enhanced the expression of both pro- and anti-inflammatory cytokines in SCTs. DEX treatment reduced IL-8 levels in control and LPS-treated cultures by 70,90%. Conclusion, Cytokine expression in SCTs was enhanced by LPS treatment and this effect was suppressed by glucocorticoid treatment. This suggests that inflammatory compounds may alter cytokine expression in the syncytium throughout gestation. [source] Progesterone Regulates IL12 Expression in Pregnancy Lymphocytes by Inhibiting Phospholipase A2AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2003G. Par Par G, Geli J, Kozma N, Varga P, Szekeres-Bartho J. Progesterone regulates IL12 expression in pregnancy lymphocytes by inhibiting phospholipase A2. AJRI 2003; 49:1,5 © Blackwell Munksgaard, 2003 PROBLEM: Progesterone-induced blocking factor (PIBF) is one of the pathways that mediate the immunological effects of progesterone. PIBF inhibits natural killer (NK) cytotoxic activity. Recently we showed that neutralization of PIBF results in an increased interleukin (IL)-12 expression, which is corrected by cyclooxygenase inhibitors. As exogenous arachidonic acid (AA) voids the NK blocking effect of PIBF, it is likely that PIBF acts before the level of the cyclooxygenase enzyme. Therefore in this study we investigated the effect of PIBF neutralizing antibody and simultaneous phospholipase A2 inhibitor quinacrine (Q) treatment on IL-12 production. METHODS: Pregnancy lymphocytes were treated with anti-PIBF antibody or lipopolysaccharide (LPS) as a positive control, in the presence or absence of Q. IL-12 expression by PBMC was detected by immunocytochemistry. RESULTS: Neutralization of PIBF as well as LPS treatment resulted in an increased IL-12 expression, which was corrected by simultaneous Q treatment. Pre-treatment of lymphocytes with progesterone prevented the stimulating effect of LPS on IL-12 production. CONCLUSION: Progesterone binding of the lymphocytes is followed by the release of PIBF that inhibits AA release. The subsequent block of prostaglandin synthesis reduces IL-12 production and results in a lowered cytotoxic NK activity, which may contribute to a normal pregnancy outcome. [source] Influence of orally administered bovine lactoferrin on lipid metabolism in lipopolysaccharide-injected preruminant calvesANIMAL SCIENCE JOURNAL, Issue 3 2009Shiro KUSHIBIKI ABSTRACT The aim of this study was to investigate the influence of oral lactoferrin (LF) administration on lipid metabolism changes in calves given lipopolysaccharide (LPS). Twenty-one 4-day-old Holstein calves were divided into three groups, with each group receiving one of three oral doses of LF (0, 1, 3 g/day) for 10 consecutive days (day ,10 to day ,1). All calves were intravenously injected with LPS (50 ng/kg BW) on day 0, the day after LF treatment ended. Plasma triglyceride concentrations were lower (P < 0.05) in the LF-treated calves than in the control calves given 0 g/day of LF at 12 and 24 h after LPS injection. Plasma NEFA concentrations were elevated between 6 and 24 h after LPS treatment. At 12 h, the concentration of plasma NEFA was lower (P < 0.05) in the calves given LF 3 g/day than in the control calves. On day 0, plasma total cholesterol and phospholipid concentrations tended to be lower in the LF groups administered 1 and 3 g of LF/day than in the control group, but did not differ significantly among the groups. The plasma very-low-density and low-density lipoprotein concentrations were lower (P < 0.05) at 12, 24, and 72 h in the LF groups than in the control calves. The concentrations of plasma high-density lipoprotein tended to be lower in the LF groups than in the control group between day 0 and 96 h, though there were no significant group differences. The concentration of plasma interleukin-1, was lower (P < 0.05) in the calves fed LF 3 g/day than in the control calves at 2 and 12,48 h after LPS injection. These data suggest that LF inhibits LPS-induced alterations in lipid metabolism in preruminant calves. [source] Involvement of cannabinoids in the cardioprotection induced by lipopolysaccharideBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001Caroline Lagneux We have examined the involvement of the endocannabinoid system in the cardioprotection triggered by lipopolysaccharide (LPS). Rats were treated with saline or LPS (10 ,g Kg,1). 24 h later, hearts were excised, retrogradely perfused, submitted to a low-flow ischaemia (0.6 ml min,1) for 90 min and reperfused for 60 min. Some hearts were perfused with either SR 141716A (a cannabinoid CB1, receptor antagonist 1 ,M), SR 144528 (a CB2 receptor anagonist ,M), NNLA (3 ,M) or sodium nitroprusside (1 ,M) 5 min before ischaemia and during the ischaemic period. The cardioprotective effects of LPS treatment, in terms of infarction and functional recovery, were not altered by the perfusion of SR 141716A but abolished by both SR 144528 and NNLA. Finally, SR 144528 abolished the beneficial effects of SNP perfusion. Our results suggest an involvement of endocannabinoids, acting through the CB2 receptors, in the cardioprotection triggered by LPS against myocardial ischaemia. This could be attributed to a relationship between cannabinoids and NO. British Journal of Pharmacology (2001) 132, 793,796; doi:10.1038/sj.bjp.0703902 [source] Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2010J. P. Burke Background: Fibroblasts play a critical role in intestinal wound healing. Lipopolysaccharide (LPS) is a cell wall component of commensal gut bacteria. The effects of LPS on intestinal fibroblast activation were characterized. Methods: Expression of the LPS receptor, toll-like receptor (TLR) 4, was assessed in cultured primary human intestinal fibroblasts using flow cytometry and confocal microscopy. Fibroblasts were treated with LPS and/or transforming growth factor (TGF) ,1. Nuclear factor ,B (NF,B) pathway activation was assessed by inhibitory ,B, (I,B,) degradation and NF,B promoter activity. Fibroblast contractility was measured using a fibroblast-populated collagen lattice. Smad-7, a negative regulator of TGF-,1 signalling, and connective tissue growth factor (CTGF) expression were assessed using reverse transcriptase,polymerase chain reaction and western blot. The NF,B pathway was inhibited by I,B, transfection. Results: TLR-4 was present on the surface of intestinal fibroblasts. LPS treatment of fibroblasts induced I,B, degradation, enhanced NF,B promoter activity and increased collagen contraction. Pretreatment with LPS (before TGF-,1) significantly increased CTGF production relative to treatment with TGF-,1 alone. LPS reduced whereas TGF-,1 increased smad-7 expression. Transfection with an I,B, plasmid enhanced basal smad-7 expression. Conclusion: Intestinal fibroblasts express TLR-4 and respond to LPS by activating NF,B and inducing collagen contraction. LPS acts in concert with TGF-,1 to induce CTGF. LPS reduces the expression of the TGF-,1 inhibitor, smad-7. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Therapeutic Effects and Anti-inflammatory Mechanisms of Heparin on Acute Lung Injury in RabbitsACADEMIC EMERGENCY MEDICINE, Issue 7 2008Meitang Wang MD Abstract Objectives:, The objectives were to investigate the potential beneficial effects and molecular mechanisms of heparin and low-molecular-weight heparin (LMWH) on acute lung injury (ALI). Methods:, Forty-eight rabbits were randomized into four groups: normal control group (Group A), lipopolysaccharide (LPS) group (Group B), LPS + heparin group (Group C), and LPS + LMWH group (Group D). The rabbit ALI model was established by intravenous (IV) injection with LPS. Alveolar,arterial O2 difference (PA-aO2), serum tumor necrosis factor , (TNF-,), circulating p38 mitogen-activated protein kinase (p38 MAPK) levels, lung nuclear factor (NF)-,B levels, and lung dry/wet (D/W) ratio were measured, and the lung injury scores were calculated. Results:, Lipopolysaccharide caused significant increases in PA-aO2, serum TNF-,, expression of p38 MAPK in polymorphonuclear neutrophils (PMNs), the lung injury scores, and nuclear factor-,B (NF-,B) activity in the lung tissue and caused a decrease in lung D/W ratio. A positive linear correlation was found between p38 MAPK and TNF-, at 1, 2, 4, and 6 hours (r = 0.68, 0.92, 0.93, and 0.93, respectively) and between NF-,B and p38 MAPK and TNF-, at 6 hours (r = 0.94 and 0.83, respectively). IV heparin or LMWH given after LPS treatment attenuated these changes in inflammatory response, oxygenation, p38 MAPK expression, and NF-,B activation. Conclusions:, The anti-inflammatory mechanisms of heparin in ALI may be inhibiting p38 MAPK and NF-,B activities, and then TNF-, overexpression, thus alleviating the inflammatory reaction. [source] Blockade of Kupffer cells by gadolinium chloride or dichloromethylene diphosphonate influences hepatic microcirculation after sepsis and haemorrhagic shockBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2000C. Herzog Background The liver plays a key role in the host defence response after haemorrhagic shock,resuscitation (H/R) and sepsis. Kupffer cells (KCs) have been shown to be a trigger and motor of the subsequent inflammatory response syndrome. This may lead to hepatocellular dysfunction, microcirculatory alterations and liver injury involving, for example, tumour necrosis factor ,, interleukin (IL) 1 and IL-6. In a double-blind study the effect of KC blockade with either gadolinium chloride or liposome-entrapped dichloromethylene diphosphonate (DMD) on hepatic microvascular flow after H/R and sepsis was investigated. Methods After pretreatment with intravenous gadolinium chloride 10 mg kg,1, DMD 1 mg kg,1 or saline 24 h before induction of shock, male Sprague-Dawley rats (n = 6,10 per group and time) were subjected to either haemorrhagic shock (mean arterial pressure 40 mmHg) for 60 min followed by resuscitation or lipopolysaccharide (LPS) 1 mg kg,1 intravenously. Microvascular flow was assessed by intravital microscopy of fluorescence-marked leucocytes in liver sinusoids at baseline, and 1, 6 and 12 h after shock induction. Results In saline groups, the mean(s.d.) leucocyte flow was significantly (P < 0·05) higher at 1 h (20 759(2901) ,m3 s,1) and 6 h (16 278(2916) ,m3 s,1) after H/R as well as at 6 h after LPS (17 661(3949) ,m3 s,1) compared with the baseline value (13 509(1580) ,m3 s,1). Animals pretreated with gadolinium chloride showed a significant flow increase compared with baseline (11 797(1124) ,m3 s,1) at l h following H/R (26 269(5909) ,m3 s,1). In DMD-pretreated animals leucocyte flow showed no significant change over time, following either H/R or LPS treatment. However, flow was significantly higher at baseline (18 054(998) ,m3 s,1) versus gadolinium chloride and saline groups. In addition, DMD-treated animals showed higher flow values 1 h after LPS challenge (20 665(2337) ,m3 s,1) compared with gadolinium chloride (13 110(1224) ,m3 s,1) and saline (15 311(800) ,m3 s,1) groups. Similarly, at 12 h after H/R the DMD group (21 782(1887) ,m3 s,1) had higher flow values than the gadolinium chloride (14 026(1616) ,m3 s,1) and saline (15 999(3175) ,m3 s,1) groups. Conclusion These results imply a significant influence of KCs on regulation of microvascular perfusion in liver sinusoids under normal conditions as well as after H/R and sepsis. The data indicate differential pathways and effects of blocking KCs by gadolinium chloride and DMD. © 2000 British Journal of Surgery Society Ltd [source] | |||||||||||||||||||||||||