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)

Intrahepatic cholestasis in the setting of extrahepatic bacterial infection has been attributed to the effects of endotoxin and cytokines such as tumor necrosis factor-alpha (TNF-alpha) on bile acid transport. To define the mechanism of sepsis-associated cholestasis, taurocholate transport was examined in basolateral (bLPM) and canalicular (cLPM) rat liver plasma membrane vesicles derived from control and endotoxin [lipopolysaccharide (LPS)]-treated animals and in plasma membrane vesicles prepared after TNF-alpha treatment. Na(+)-dependent [3H]taurocholate uptake and both membrane-potential-dependent and ATP-dependent [3H]taurocholate transport were reduced in bLPM and cLPM vesicles, respectively, after LPS treatment. In membrane vesicles from TNF-alpha-treated animals, Na(+)-dependent [3H]taurocholate uptake was also reduced. Northern blot hybridization, using cDNA probes for the putative sinusoidal bile acid transporter (Ntcp) and canalicular ecto-adenosinetriphosphatase, demonstrated decreased mRNA levels after LPS and TNF-alpha treatment. Immunoblot analysis of membrane extracts from LPS-treated animals revealed decreased levels of these putative bile acid transporters. Impaired bile acid transport at the sinusoidal and canalicular membrane domains by these and other mediators of the inflammatory response may account for sepsis-associated cholestasis.
 ...
PMID:Effect of endotoxin on bile acid transport in rat liver: a potential model for sepsis-associated cholestasis. 876 Jan 17

Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in an immune-mediated demyelinating disease (TMEV-IDD) similar to human multiple sclerosis (MS). Although the etiology of MS remains unknown, a role of an infectious agent has been implicated in its onset. Previously we have shown the ability of bacterial lipopolysaccharide (LPS) to alter susceptibility to TMEV-IDD in genetically resistant C57BL/6 mice. In this study, the potential of LPS to alter pathogenicity of a low/non-pathogenic variant of TMEV was investigated. After intraperitoneal treatment of genetically susceptible SJL/J mice with LPS before and during viral infection, 80-100% of the mice developed clinical symptoms, while without LPS treatment none of the mice were affected. However, clinical severity in these LPS-treated mice was much milder than the level induced by the wild type pathogenic virus. Increased susceptibility to the disease after LPS treatment did not correlate with splenic T cell proliferative responses against viral antigens. However, by reverse transcriptase polymerase chain reaction (RT-PCR) analyses, an early increase in the production of Th1-type proinflammatory cytokine messages (e.g., interferon-gamma [IFN-gamma] and enhancement of viral persistence was observed in the CNS of LPS-treated, virus-infected animals as compared to mice infected with the variant virus alone. These results indicate that environmental factors such as a bacterial infection (e.g., LPS) promoting proinflammatory cytokine production can significantly enhance the pathogenicity of demyelination induced by a normally non-pathogenic virus.
 ...
PMID:Treatment with lipopolysaccharide enhances the pathogenicity of a low-pathogenic variant of Theiler's murine encephalomyelitis virus. 889 89

Nitric oxide (NO) has been shown to play a significant role in inflammation. To clarify the role of NO in acute pancreatitis, we investigated the serum concentrations of NO chi (NO2- plus NO3-) and tumor necrosis factor-alpha (TNF-alpha) and the grade of pancreatitis in cerulein-induced pancreatitis in mice pretreated with lipopolysaccharide (LPS) or not. LPS pretreatment aggravated the cerulein pancreatitis in association with a transient increase in serum TNF-alpha, which was followed by a gradual elevation of serum NO chi. This elevation of serum NO chi concentration was inhibited by the NO synthase inhibitor NG-nitro-L-arginine (L-NNA). In addition, the activity of NADPH-diaphorase (NADPH-d), a marker for NO synthase, appeared in the peritoneal macrophages of LPS-pretreated mice after the induction of pancreatitis. No elevation of serum NO chi or appearance of NADPH-d activity in peritoneal cells was found in mice without LPS pretreatment. Administration of L-NNA enhanced the elevation of pancreatitis-induced serum amylase in mice untreated with LPS, while L-NNA inhibited the elevation in LPS-pretreated mice. The effects of L-NNA were reversed by the administration of L-arginine but were not affected by D-arginine. These results suggested that (a) inflammatory cells may not be fully activated to produce excessive NO in uncomplicated edematous pancreatitis, and (b) edematous pancreatitis may be aggravated by excessively produced NO if bacterial infection is complicated and inflammatory cells are activated to express inducible NO synthase.
 ...
PMID:The role of nitric oxide in mouse cerulein-induced pancreatitis with and without lipopolysaccharide pretreatment. 892 22

The effect of a prolonged low dose infusion of bacterial lipopolysaccharide (LPS) on acute phase-like reactions was examined in heifers. LPS (2 micrograms kg-1 dissolved in 100 ml water), or saline was infused (at 1 ml min-1) intravenously for 100 minutes and blood samples were taken at various times before, during and after the infusion. The serum concentrations of tumour necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and serum amyloid A (SAA) and the rectal temperature increased in response to the LPS infusion. Serum TNF alpha increased before the increases in IL-1 beta and IL-6 and remained high from 20 minutes after the onset of the infusion until the end of the sampling period (six hours). The LPS-induced increases in serum IL-1 beta and IL-6 were biphasic. Plasma cortisol and lactate concentrations also increased, and plasma glucose and beta-hydroxybutyrate concentrations decreased in response to the LPS infusion. The similarity of these reactions to changes observed in response to bacterial infections shows that the prolonged infusion of low doses of LPS is a good model for studying the acute phase response to Gram-negative bacterial infection in heifers.
 ...
PMID:Characterisation of the acute phase response of heifers to a prolonged low dose infusion of lipopolysaccharide. 893 57

Imipenem and ceftazidime have different specificities for penicillin-binding proteins and cause a differential release of lipopolysaccharide (LPS) from gram-negative bacteria in vitro. In studies in mice made leukopenic by the administration of cyclophosphamide, the innate relative resistance to the lethal effects of LPS was not significantly changed, but these animals became highly sensitized to bacterial infection. When leukopenic mice were challenged with graded doses of Escherichia coli O111:B4, an LD50 was achieved at a dose of approximately 10(6) cfu. Administration of either antibiotic resulted in a shift in the LD50 of approximately 500-fold, in contrast to D-galactosamine-treated LPS-sensitized mice, in which a < 10-fold increase in the LD50 was observed with antibiotic therapy. Further, if mice were made LPS-sensitive with D-galactosamine, no differences between leukopenic and normal mice were noted with antibiotic therapy.
 ...
PMID:Bacteremia versus endotoxemia in experimental mouse leukopenia--role of antibiotic chemotherapy. 894 Feb 15

Previously, we found that the antibody titer belonging to the IgM class produced against the bacterial antigen (Lipid A) was elevated in sera from patients with primary biliary cirrhosis (PBC). On the other hand, the targets of the mitochondrial autoantibodies have been identified as being components of the pyruvate dehydrogenase complex (PDH). We tried to produce an experimental animal model for the investigation of the association between hepatic bile duct alteration and bacterial infection. Female C57/BL mice, aged 4 weeks, were used. An emulsion consisting of lipopolysaccharide (LPS) derived from Salmonella minnesota Re595, PDH, and Freund's adjuvant was prepared. This emulsion was subcutaneously injected on the back of the mice. The mice were divided into a control group (n = 5), a group given LPS (n = 5) alone, those given PDH alone (n = 5), and those given a combination of LPS and PDH (n = 5). The antigens were administered once a week every week with a maximum duration of administration of 24 weeks. The serum levels of IgM after 24 weeks in the LPS and LPS + PDH groups were 2.5 times higher than those in the control and PDH groups. The light microscopic findings of liver tissue revealed that infiltration of lymphocytes and plasma cells in the portal area, proliferation of the bile duct, and degeneration of the biliary epithelial cells were more prominent in the PDH and LPS + PDH groups than in the other groups. These results indicate that our animal model may be useful in investing the pathogenesis of PBC.
 ...
PMID:An experimental animal model of primary biliary cirrhosis induced by lipopolysaccharide and pyruvate dehydrogenase. 894 37

Bacterial infection causes fever, an adaptive but potentially self-destructive response, in the host. Also activated are counterregulatory systems such as the pituitary-adrenal axis. Antipyretic roles have also been postulated for certain endogenous central neuropeptides, including the melanocortins (alpha-MSH-related peptides). To test the hypothesis that endogenous central melanocortins have antipyretic effects mediated by central melanocortin receptors (MCRs), we determined the effect of intracerebroventricular injection of a synthetic MCR antagonist, Ac-Nle4,c-[Asp5,DNal(2')7,Lys10]alpha-MSH(4-10)-NH2 (SHU-9119) in endotoxin-challenged rats. The efficacy and specificity of SHU-9119 as an MCR antagonist in the rat was first validated in vitro and in vivo. In vitro, in heterologous cells expressing either rat MC3-R or MC4-R, the major MCR subtypes expressed in brain, SHU-9119 showed no intrinsic agonism, but it inhibited alpha-MSH-induced cAMP accumulation (IC50 = 0.48 +/- 0.19 and 0.41 +/- 0.28 nM, respectively) and [125I]-[Nle4,DPhe7]-alpha-MSH binding (IC50 = 1.0 +/- 0.1 and 0.9 +/- 0.3 nM, respectively). In vivo, exogenous alpha-MSH (180 pmol) inhibited fever in rats when administered intracerebroventricularly 30 min after Escherichia coli lipopolysaccharide (LPS) (25 microg/kg, i.p.). When co-injected with alpha-MSH, SHU-9119 (168 pmol, i.c.v.) prevented the antipyretic action of exogenous alpha-MSH. In contrast, neither alpha-MSH nor SHU-9119, alone or in combination, affected body temperatures in afebrile rats. In LPS-treated rats, intracerebroventricular injection of SHU-9119 significantly increased fever, whereas intravenous injection of the same dose of SHU-9119 had no effect. Neither intracerebroventricular nor intravenous SHU-9119 significantly affected LPS-stimulated plasma ACTH or corticosterone levels. The results indicate that endogenous central melanocortins exert an antipyretic influence during fever by acting on MCRs located within the brain, independent of any modulation of the activity of the pituitary-adrenal axis.
 ...
PMID:Antipyretic role of endogenous melanocortins mediated by central melanocortin receptors during endotoxin-induced fever. 909 67

Interleukin-12 (IL-12) is a proinflammatory cytokine produced by antigen-presenting cells in response to many microbial infections. IL-12 plays an important role in the generation of T helper type-1 cells, which favor cell-mediated immune response. IL-12 is composed of two different subunits, p40 and p35, whose expression can be regulated concomitantly or differentially. Monocytic cells, the major producers of IL-12, can be primed by interferon-gamma (IFN-gamma) to produce optimal amounts of IL-12 in response to LPS stimulation as a consequence of bacterial infection. The priming effect is exerted primarily at the transcriptional level on the p40 promoter in conjunction with the effects of LPS, possibly by inducing specific transcription factors, which individually have no direct effect but which cooperatively can activate the promoter. We examined in detail one of these DNA-protein interactions observed around an Ets-2 element situated at -211/-207 of the p40 promoter, which is known to be a functionally critical site. This region interacts with a nuclear complex termed F1 that appears to be highly inducible by either IFN-gamma treatment for 16 h or lipopolysaccharide stimulation for 8 h. F1 binding to the Ets-2 site requires a considerable amount of spacing around the Ets-2 site, as revealed by gel mobility shift and in vitro methylation assays. Supershift experiments and DNA affinity purification indicated that both Ets-2 and a novel, antigenically related protein with an approximate molecular mass of 109 kDa are part of the F1 complex, together with additional components including IRF-1 and c-Rel. This novel protein is designated GLp109 for its inducibility by IFN-gamma or lipopolysaccharide. Its possible role in the activation of the IL-12 p40 promoter is discussed.
 ...
PMID:Identification and characterization of a novel Ets-2-related nuclear complex implicated in the activation of the human interleukin-12 p40 gene promoter. 909 78

Cell-free hemoglobin (Hb) is being developed as an erythrocyte substitute. We have previously demonstrated that cell-free Hb is an endotoxin-binding protein which disaggregates endotoxin and subsequently increases the biological activity of endotoxin in several in vitro assays. Because much of the morbidity and mortality associated with gram-negative bacterial infection is the result of pathophysiologic responses to bacterial lipopolysaccharide (LPS; endotoxin), we studied the effect of Hb on LPS-mediated mortality. Hb infused intravenously into mice before, coincident with, or after intraperitoneal LPS injection substantially increased LPS-related mortality from <5% to 50 to 70% 24 h after administration of LPS and from 50% to 60 to 90% at 48 h. Enhanced mortality was observed over a range of doses of injected LPS. At a given LPS dose, enhancement of mortality was shown to be dependent on the dose of Hb administered. Unmodified native human Hb, alpha-alpha-cross-linked human Hb, and beta-beta-cross-linked human or bovine Hb all were shown to enhance LPS-mediated mortality. Depressed reticuloendothelial cell function may have contributed to the enhanced mortality from LPS in the presence of Hb. Therefore, Hb-based blood substitutes, which are currently undergoing clinical trials, may intensify the potentially fatal effects of the sepsis syndrome in patients with trauma, infection, or hypotension who receive Hb for erythrocyte replacement.
 ...
PMID:Hemoglobin increases mortality from bacterial endotoxin. 911 60

Cachexia and a decreased immune function are negative prognostic factors for cancer patients. While the decreased immunity results in a greater susceptibility to bacterial infection, the response of the host to the resulting infection is not clear. The experiments reported here were designed to evaluate the toxicity of endotoxin to rats with a transplantable Ward colon tumor (WCT) and to evaluate the mechanism of the observed increase in lethal toxicity. The lethal toxicity of endotoxin (lipopolysaccharide, LPS) at 5 mg/kg, i.p. was evaluated in the first of two experiments. Rats received LPS and were observed for morbidity and weight loss for a period of 11 days. A second experiment was done to evaluate the effect of LPS on the plasma nitrate/nitrite concentrations and plasma indicators of host tissue dysfunction. LPS was administered as previously described but blood and tissues were collected 5 h after LPS administration. LPS resulted in the death of 1 of 12 nontumor-bearing (NTB) rats and a transient weight loss in the survivors. This same dose of LPS, however, resulted in death for 10 of 12 WCT rats with tumor burdens less than 4% of body weight. The response of WCT rats 5 h after LPS was then compared with that of age-matched NTB rats. Plasma albumin concentrations were not affected by LPS in NTB rats but were significantly decreased in WCT rats. Peripheral blood gases were not consistently affected by LPS in either group. Peripheral blood white cell counts, except monocytes, were significantly decreased by LPS in both groups. Monocyte counts in peripheral blood were further reduced in WCT rats compared with NTB rats receiving LPS. The presence of the WCT significantly enhanced the LPS-associated increase in spleen weight. Liver weights were lower in LPS rats but there was no effect of the presence of WCT. The LPS-associated increase in plasma nitrate/nitrite concentration was enhanced by the WCT. The plasma arginine and citrulline concentrations were altered in a manner consistent with an increase in nitric oxide synthesis. An increase in plasma ornithine concentration suggests an increase in arginine metabolism by arginase. The plasma concentration of alanine aminotransferase was significantly elevated when WCT rats received LPS, suggesting enhanced hepatic dysfunction. The plasma blood urea nitrogen concentration was elevated by LPS to a greater extent in the WCT rats than in the NTB controls, indicating increased renal dysfunction. These results demonstrate that the Ward colon tumor increases the host lethal response to the endotoxin, a toxic product of bacterial infections. The mechanisms of lethality may include an increased nitric oxide synthesis in WCT rats and enhanced liver and renal toxicity.
 ...
PMID:Influence of the Ward colon tumor on the host response to endotoxin. 917 90


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