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)

The purpose of this study was to define the differences in heat shock protein (hsp)70, albumin, alpha(-1)-acid glycoprotein (AGP), and CCAAT enhancer binding proteins (C/EBP) alpha and beta mRNA between hepatic ischemia and reperfusion, and to begin to explore C/EBP protein production. These genes have been found important in the hepatic response to lipopolysaccharide and inflammation. In two experiments, Sprague-Dawley rats underwent temporary occlusion of the median and left hepatic lobe vasculature. The first experiment included a single sham-operated group and ligation of the right hepatic lobes during reperfusion. It compared 30 and 60 min ischemia to 2 h reperfusion. The second experiment included a sham-operated group for every time point, and the right hepatic lobes were not ligated during reperfusion; a 30-min ischemia group was compared to 2-, 5-, and 24-h reperfusion groups. Total RNA from the ischemic lobes was analyzed by Northern hybridization for hsp70, albumin, AGP, and C/EBPalpha and beta. C/EBPalpha and beta proteins were compared by Western blotting. Differences in experimental design played an important role in interpretation of results. hsp70 mRNA began to increase during ischemia. Albumin mRNA remained constant during ischemia and reperfusion. The ischemic hepatocyte nucleus is not quiescent and retains the ability to upregulate certain genes, e.g., hsp70. Changes in mRNA in response to hepatic ischemia/reperfusion occur rapidly. Hepatic ischemia/reperfusion does not recapitulate the classic acute phase response; albumin is not down regulated during reperfusion.
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PMID:Early gene response to hepatic ischemia reperfusion. 866 Nov 80

Sublethal endotoxemia attenuates cardiac functional injury from global ischemia but it is unknown whether endotoxemia can protect myocardium against infarction. Furthermore, increases in myocardial catalase and heat shock protein (HSP) following endotoxemia have been associated with cardiac ischemic protection. We therefore hypothesized that a 72-hr pretreatment with endotoxin (ETX) would reduce myocardial tissue necrosis in association with augmented catalase activity and stress protein expression. Rabbits were treated with normal saline or lipopolysaccharide (Salmonella typhimurium) at 10, 5, and 1 microgram/kg doses. Three days after saline or ETX injection they were subjected to 45 min of coronary artery occlusion followed by 3 hr of reperfusion. Area of necrosis (tetrazolium staining) was normalized to anatomic risk zone size (Evans blue staining). Catalase activity was measured by a standard assay and HSP 72 was assessed by immunohistochemistry. During regional ischemia and reperfusion there were no differences in heart rate or mean arterial blood pressure between groups. ETX treated rabbits had the same risk zone size as controls. Infarct size was reduced in the ETX treated rabbits at the 10 and 5 microgram/kg doses compared with control rabbits (17.5 +/- 1.5% and 22.2 +/- 3.1% vs 45.3 +/- 2.5%; P < 0.05) but no protective effect was observed at the 1.0 micrograms/kg dose (38.0 +/- 4.6%; P > 0.05 vs control). Catalase activity was not different between control and ETX (5 microgram/kg) treated groups (997.8 +/- 59.1 U/g vs 1099.6 +/- 69.3 U/g myocardium; P > 0.05) but endotoxin induced expression of myocardial HSP 72. We conclude that a single challenge with endotoxin can induce delayed myocardial protection against infarction in vivo. This delayed cardioprotective response involves enhanced stress protein expression without changes in myocellular catalase activity.
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PMID:A single endotoxin challenge induces delayed myocardial protection against infarcation. 866 Nov 96

In many diseases, tissue hypoxia occurs in conjunction with other inflammatory processes. Since previous studies have demonstrated a role for leukocytes in ischemia/reperfusion injury, we hypothesized that endothelial hypoxia may "superinduce" expression of an important leukocyte adhesion molecule, E-selectin (ELAM-1, CD62E). Bovine aortic endothelial monolayers were exposed to hypoxia in the presence or absence of tumor-necrosis factor alpha (TNF-alpha) or lipopolysaccharide (LPS). Cell surface E-selectin was quantitated by whole cell ELISA or by immunoprecipitation using polyclonal anti-E-selectin sera. Endothelial mRNA levels were assessed using ribonuclease protection assays. Hypoxia alone did not induce endothelial E-selectin expression. However, enhanced induction of E-selectin was observed with the combination of hypoxia and TNF-alpha (270% increase over normoxia and TNF-alpha) or hypoxia and LPS (190% increase over normoxia and LPS). These studies revealed that a mechanism for such enhancement may be hypoxia-elicited decrements in endothelial intracellular levels of cAMP (<50% compared with normoxia). Addition of forskolin and isobutyl-methyl-xanthine during hypoxia resulted in reversal of cAMP decreases and a loss of enhanced E-selectin surface expression with the combination of TNF-alpha and hypoxia. We conclude that endothelial hypoxia may provide a novel signal for superinduction of E-selectin during states of inflammation.
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PMID:Hypoxia enhances stimulus-dependent induction of E-selectin on aortic endothelial cells. 869 47

Both burn injury and intestinal ischemia have been proven to induce bacterial translocation from the gut. It is still unknown, however, whether the bacteria induces immune response in these different models. To assess this, we measured in vitro IgM synthesis to peptidoglycan polysaccharide (PGPS), a ubiquitous gut bacterial antigen, after burn injury or gut ischemia-reperfusion in a mouse model. Eighty-five BALB/c mice were divided into four groups. Gut ischemia was produced by placing a vessel loop around the superior mesenteric artery at celiotomy (group Isc; n = 31). After 45 minutes, the abdomen was reopened, and the vessel loop removed. All animals had visible gut ischemia. Control mice (group Isc-C; n = 15) underwent two sham operations. Burn injury was 25% body surface area full-thickness to the dorsum (group B; n = 27). Another control group (B-C; n = 12) was also used. Animals were euthanized 24 hours after recirculation or 5 days after the burn injury. All spleens were removed, and cell suspensions prepared. Cells were cultured in 2.5 micrograms/ml lipopolysaccharide for 5 days, and anti-PGPS IgM level in the supernatant was measured by an enzyme-linked immunosorbent assay. Intestinal ischemia produced a significant rise in in vitro anti-PGPS IgM synthesis per 10(5) lymphocytes, which is the principal immunoglobulin response to infection. However, anti-PGPS IgM in mice after burn injury was significantly decreased. This decreased IgM synthesis after burn injury compared to gut ischemia may represent continued immune impairment from the burn wound, and may account for organ dysfunction related to bacterial translocation after burn injury.
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PMID:Differences in IgM synthesis to gut bacterial peptidoglycan polysaccharide after burn injury and gut ischemia. 873 68

Monophosphoryl lipid A (MLA), a derivative of the minimal substructure of lipopolysaccharide (lipid A) possesses immunomodulatory activity of the parent lipid A yet enjoys reduced toxicity. It has previously been reported that pretreatment with MLA reduces myocardial infarct size and stunning in dogs following ischemia and reperfusion. The aim of this study was to evaluate the ability of monophosphoryl lipid A (MLA) to preserve global cardiac function and peripheral hemodynamics in a rabbit model of prolonged regional ischemia (90 min), and reperfusion (6 h). An evaluation of potential mechanisms by which MLA may preserve cardiac function was also undertaken. Single dose pretreatment with MLA (35 micrograms/kg i.v.) 24 h prior to ischemia resulted in significant improvement in left ventricular developed pressure, dP/dt, rate-pressure product and mean arterial pressure during reperfusion (P < 0.05 v control). Although in this model of prolonged ischemia MLA pretreatment did not reduce infarct size (54.5 +/- 11.4% in control v 63.3 +/- 8.3% in MLA, P = N.S.), evaluation of myocardial adenylate and adenosine catabolite pools at the end of ischemia indicated a preservation of ATP and ADP and a decreased production of downstream adenosine catabolites including inosine, xanthine and uric acid. Adenosine kinase, but not 5'-nucleotidase (5'-NTase) or adenosine deaminase activity determined following reperfusion was 76% and 60% higher (P < 0.05) in non-risk and post-ischemic myocardium of MLA pretreated rabbits compared with controls. Although there was a trend toward lower tissue myeloperoxidase activity in post-ischemic myocardium from treated rabbits, the results were not significantly different from control animals. These results suggest that a 24-h pretreatment with MLA, without further treatment during ischemia or reperfusion was associated with: (1) preservation of global myocardial function during reperfusion; (2) preservation of myocardial high energy adenylates and reduced formation of adenosine catabolites during ischemia; (3) elevated myocardial adenosine kinase activity. Increased recycling of adenosine to phosphorylated nucleotides may result from MLA's affect on adenosine kinase, which could explain the drugs effect on adenylate and adenosine metabolite pools.
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PMID:Preservation of global cardiac function in the rabbit following protracted ischemia/reperfusion using monophosphoryl lipid A (MLA). 874 27

In this study, we investigated the effects of a glycine-containing diet (5%) on mortality and liver injury due to intravenous injection of endotoxin [Escherichia coli lipopolysaccharide (LPS)] in Sprague-Dawley rats in vivo. Fifty percent of the rats fed control diet died within 24 h after an intravenous injection of LPS (10 mg/kg), whereas feeding the rats glycine totally prevented mortality and markedly reduced an LPS-induced elevation of serum transaminase levels, hepatic necrosis, and lung injury. The elevation in serum tumor necrosis factor-alpha (TNF-alpha) due to LPS was also blunted and delayed significantly by glycine feeding. In a two-hit model (hepatic ischemia-reperfusion and injection of sublethal LPS), all rats fed control diet died, whereas 83% of glycine-fed animals survived with a significant reduction in transaminases and improved liver and lung histology. LPS elevated intracellular Ca2+ concentration ([Ca2+]i) in cultured Kupffer cells, an effect blocked almost completely by glycine. Glycine most likely reduces injury and mortality by preventing the LPS-induced elevation of [Ca2+]i in Kupffer cells, thereby minimizing toxic eicosanoid and cytokine production.
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PMID:A diet containing glycine improves survival in endotoxin shock in the rat. 876 Jan 12

The functional capacity of the hepatic reticuloendothelial system (RES) was studied under conditions of intestinal shock. Wistar rats underwent intestinal ischemia (60 min)-reperfusion or a sham procedure. One-half of each group received intravenous infusion of 2.6 x 10(-6) g/kg lipopolysaccharide B. Phagocytic clearance and phagocytic killing by the hepatic RES were quantitated using a double label bacteria clearance assay. Hepatic phagocytosis was unchanged 3 h after reperfusion of the ischemic intestine but hepatic killing was significantly decreased compared with the sham situation. The results were not different in animals who had received LPS B infusion. The plasma endotoxin levels correlated inversely to the hepatic killing efficiency (r = -.801) in the shocked animals given exogenous endotoxin. The decreased capacity of the hepatic RES to degrade bacteria present in the portal circulation could be an important pathophysiologic mechanism in the development of bacterial translocation.
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PMID:Hepatic reticuloendothelial system dysfunction after intestinal ischemia-reperfusion. 882 Nov 7

The etiology of chronic rejection of kidney allografts is unknown, although hyperfiltration, acute rejection, viral infection and initial graft ischemia have been implicated. To test whether endothelial activation may be the link between these factors and chronic rejection, the endotoxin (lipopolysaccharide-LPS), a potent activator of endothelial cells, was evaluated in an established chronic rejection model. Bilaterally nephrectomized Lewis recipients of orthotopically transplanted Fisher 344 kidneys were treated briefly with low dose cyclosporine (1.5 mg/kg/day x 10). Recipients were given a non-lethal dose of LPS (2 mg) i.p. at 8 weeks and compared to allografted controls treated with vehicle. Urine protein was measured every 4 weeks. Rats in the treated group were sacrificed at 12 and 16 weeks, control animals at 12, 16 and 24 weeks (20/group) and examined histologically. In the chronically rejecting control allografts, progressive interstitial and glomerular sclerosis and vascular intimal proliferation had become apparent by 12 weeks. Infiltration of glomeruli, particularly by macrophages (M phi), and the coincident presence of cytokines were prominent, peaking at 16 weeks. LPS treatment accelerated and intensified these changes; proteinuria was more pronounced (16 weeks: 79 mg/24 h vs. 49 mg/24 h, p < 0.05). Numbers of infiltrating M phi peaked at 12 weeks in LPS treated hosts (69 c/FV vs. 27 c/FV in untreated controls, p < 0.01), accompanied by an increased upregulation of MHC class II and cytokine expression, particularly TNF alpha and PDGF around arteries and areas of infiltration. BY 16 weeks, 35 +/- 3% of glomeruli in LPS treated recipients had become sclerotic vs. 15 +/- 6% (p < 0.05) in controls, again associated with increased expression of cytokines (PDGF, TNF alpha, TGF beta), adhesion molecules (ICAM-1) and extracellular matrix proteins. Overall, the extent of chronic rejection of grafts in LPS treated rats at 16 weeks was similar to that developing in non-treated rats at 24 weeks. Activation of graft endothelium and/or host leucocytes increased the pace of graft infiltration and the expression of cytokines and other molecules. These events accelerate the process of chronic rejection.
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PMID:Infections and reduced functioning kidney mass induce chronic rejection in rat kidney allografts. 883 48

The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
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PMID:Intercellular adhesion molecule-1. 883 67

Sepsis is intricately associated with mesenteric ischemia. The remote complications of mesenteric ischemia are essentially those of sepsis, whether as a cause or as a consequence. Experimental endotoxic shock induces bowel hypoperfusion, erythrocyte extravasation and intestinal necrosis. The effects of pentoxifylline, rolipram and denbufylline, three phosphodiesterase inhibitors, were studied on endotoxin-induced bowel erythrocyte extravasation and intestinal and renal hypoperfusion, in conscious rats and anaesthetized dogs, respectively. Two hours after lipopolysaccharide i.v. injection in rats, erythrocyte extravasation was evident throughout the intestinal musculature and mucosa, apparently without affecting lungs, heart, kidneys, liver or pancreas. Pretreatment with the non-selective phosphodiesterase inhibitor, pentoxifylline, or selective phosphodiesterase IV inhibitors such as denbufylline or rolipram reduced intestinal haemoconcentration. In the anaesthetized dog, pentoxifylline and denbufylline both inhibited the E. coli lipopolysaccharide-induced mesenteric blood flow fall, without affecting renal blood flow or cardiac index. In conclusion, phosphodiesterase inhibitors protected from intestinal damage and bowel hypoperfusion after lipopolysaccharide challenge. This action may thus play a role in the protective effects against endotoxin-induced lethal toxicity previously described for phosphodiesterase inhibitors.
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PMID:Inhibition of lipopolysaccharide-induced bowel erythrocyte extravasation in rats, and of mesenteric hypoperfusion in dogs, by phosphodiesterase inhibitors. 890 Oct 18


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