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)

Oxygen therapy remains the main component of the ventilation strategy for treatment of patients with acute lung injury. Hyperbaric oxygen therapy (HBO(2)) is the intermittent administration of 100% oxygen at pressure greater than sea level and has been applied widely to alleviate a variety of hypoxia-related tissue injuries. The purpose of this study was to evaluate the effect of hyperbaric oxygen on acute lung injury induced by intratracheal spraying of lipopolysaccharide (LPS) in rats. Male Sprague-Dawley rats underwent implantation of a carotid artery catheter under general anesthesia. Aerosolized LPS was delivered twice into the lungs via intratracheal puncture. Animals were either breathing room air (n = 27) or subjected to hyperbaric oxygen (HBO(2)) exposure (n = 27) 1 h after LPS spraying. Acute lung injury was evaluated 5 h and 24 h later. Compared with the control group, intratracheal spraying of LPS caused profound hypoxemia, greater wet/dry weight ratio (W/D) of the lung (5.67 +/- 0.22 vs. 4.98 +/- 0.19), and higher protein concentration (1706 +/- 168 vs. 200 +/- 90 mg/L) and LDH activity (129 +/- 30 vs. 46 +/- 15, mAbs/min) in bronchoalveolar lavage (BAL) fluid. Intratracheal spraying of LPS also caused significant WBC sequestration in the lung tissue. HBO2 treatment significantly reverted hypoxemia, reduced lung injury measures evaluated at 5 and 24 h, and enhanced 24-h animal survival rate (chi = 5.08, P = 0.024). The malondialdehyde (MDA) concentrations in lung tissue and serum were both increased after LPS spraying. Neither single HBO(2) therapy nor five sequential daily treatments enhanced MDA production in lung tissue or serum. Our results suggested that hyperbaric oxygen might reduce acute lung injury caused by intratracheal spraying of LPS in rats. This treatment modality is not associated with enhancement of oxidative stress to the lung.
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PMID:Effect of hyperbaric oxygen on endotoxin-induced lung injury in rats. 1517 39

The prostaglandin (PG) E2 receptor subtype EP4 has been found to mediate regulation of inflammatory cytokines in macrophages and neutrophils in vitro by PGE2. Yet the role of EP4 receptors in endotoxin shock in vivo and whether EP4 activation is a beneficial treatment are not clear. We tested the effect of an EP4 agonist on hemodynamic changes and production of inflammatory cytokines in a rat endotoxin-induced shock model. In rats under pentobarbital anesthesia, lipopolysaccharide (LPS) was injected, and an EP4 agonist (ONO-AE1-329) was administered at one of three concentrations (1, 3, or 10 microg/kg bolus i.v. hourly). Mean arterial pressure (MAP) was monitored throughout the experiment, and pressor responses to norepinephrine were determined 6 h after LPS injection. Serum tumor necrosis factor (TNF)-alpha and serum interleukin (IL)-6 were measured 1 h and 6 h after LPS injection. Venous nitrosyl hemoglobin (NO-Hb) concentration was measured by electron spin resonance. Expression of mRNAs encoding TNF-alpha and inducible nitric oxide synthase (iNOS) in the left ventricle and descending aorta was determined with a real-time reverse transcription polymerase chain reaction. As time progressed, LPS significantly depressed MAP and decreased reactivity to norepinephrine. Infusion of higher doses of the EP4 agonist at 3 and 10 microg/kg/h attenuated LPS-induced hypotension and hyporeactivity to norepinephrine. LPS significantly increased serum concentrations of TNF-alpha and IL-6, and higher doses of EP4 agonist significantly attenuated these increases. Left ventricular and aortic expression of mRNAs encoding TNF-alpha and iNOS was increased by LPS; again, EP4 agonist at higher doses attenuated the increases. LPS-induced production of inflammatory mediators and cardiovascular depression were attenuated by EP4 agonist administration in an in vivo endotoxin shock model. Anti-inflammatory effects thus would be involved in protection by EP4 agonist against cardiovascular depression in endotoxin shock.
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PMID:A prostaglandin E2 receptor subtype EP4 agonist attenuates cardiovascular depression in endotoxin shock by inhibiting inflammatory cytokines and nitric oxide production. 1520 6

Most experimentally induced fevers are acute, usually lasting approximately 6-12 h, and thus do not mimic chronic natural fevers, which can extend over several days or more. To produce a model of chronic natural fever, we infused eight goats (Capra hircus) intravenously with 2 ml of 2 x 10(11) cell walls of Staphylococcus aureus (S. aureus) for 6 days using osmotic infusion pumps (10 microl/h) while measuring changes in body temperature, behavior, and plasma cortisol concentration. Seven control animals were infused with sterile saline. Abdominal temperature-sensitive data loggers and osmotic infusion pumps were implanted under halothane anesthesia. To compare our new model with existing models of experimental fever, we also administered 2-ml bolus intravenous injections of 2 x 10(11) S. aureus cell walls, 0.1 microg/kg lipopolysaccharide (Escherichia coli, serotype 0111:B4), and sterile saline in random order to six other goats. Bolus injection of lipopolysaccharide and S. aureus induced typical acute phase responses, characterized by fevers lasting approximately 6 h, sickness behavior, and increased plasma cortisol concentration. Infusion of S. aureus evoked prolonged fevers, which lasted for approximately 3 days, starting on day 4 of infusion (ANOVA, P < 0.05), and did not disrupt the normal circadian rhythm of body temperature. However, pyrogen infusion did not cause plasma cortisol concentration to rise (ANOVA, P > 0.05) or the expression of sickness behavior. In conclusion, infusion of S. aureus produced a fever response resembling that of sustained natural fevers but did not elicit the cortisol and behavioral responses that often are described clinically and during short-term experimental fevers.
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PMID:Body temperature, behavior, and plasma cortisol changes induced by chronic infusion of Staphylococcus aureus in goats. 1521 86

The peptide hormone prolactin (PRL) is produced by specialized cells in the anterior pituitary gland and in a number of sites outside the pituitary. Its biological actions consist of various roles in reproduction, lactation, and of a number of homeostatic biological activities that also include immune functions. Elevated serum PRL concentrations often correlate with abnormalities in immune responses. To determine the influence of PRL on human immune cells, human whole blood cultures were stimulated with lipopolysaccharide (LPS), supplemented with various concentrations of human recombinant PRL. We found that PRL, at concentrations achievable during pregnancy, anesthesia and medication, significantly amplified interleukin (IL)-12 and tumor necrosis factor-alpha (TNF-alpha) synthesis in LPS-stimulated cultures, in a dose-dependent manner. Conversely, synthesis of the anti-inflammatory cytokine IL-10 only increased significantly at very high concentrations of supplemented PRL. PRL alone was not able to induce any measurable secretion of TNF-alpha, IL-10, or IL-12 in non-stimulated, whole blood cultures. However, we demonstrated that PRL, by itself or in combination with LPS, causes an increase in the binding activity of the transcription factors nuclear factor-kappaB (NFkappaB) and interferon regulatory factor-1 (IRF-1), which are known to promote TNF-alpha and IL-12 secretion. These data suggest that PRL promotes pro-inflammatory immune responses via NFkappaB and IRF-1, which may affect pathophysiological processes in physiological hyperprolactinemic states.
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PMID:Prolactin triggers pro-inflammatory immune responses in peripheral immune cells. 1531 67

Ketamine is an intravenous anesthetic agent. Clinically, induction of anesthesia with ketamine can cause immunosuppression. Macrophages play important roles in host defense. In this study, we attempted to evaluate the effects of ketamine on macrophage functions and its possible mechanism using mouse macrophage-like Raw 264.7 cells as the experimental model. Exposure of macrophages to 10 and 100 microM ketamine, which correspond to 0.1 and 1 times the clinically relevant concentration, for 1, 6, and 24 h had no effect on cell viability or lactate dehydrogenase release. When the administered concentration reached 1000 microM, ketamine caused a release of lactate dehydrogenase and cell death. Ketamine, at 10 and 100 microM, did not affect the chemotactic activity of macrophages. Administration of 1000 microM ketamine in macrophages resulted in a decrease in cell migration. Treatment of macrophages with ketamine reduced phagocytic activities. The oxidative ability of macrophages was suppressed by ketamine. Treatment with lipopolysaccharide induced TNF-alpha, IL-1beta, and IL-6 mRNA in macrophages. Administration of ketamine alone did not influence TNF-alpha, IL-1beta, or IL-6 mRNA production. Meanwhile, cotreatment with ketamine and lipopolysaccharide significantly inhibited lipopolysaccharide-induced TNF-alpha, IL-1beta, and IL-6 mRNA levels. Exposure to ketamine led to a decrease in the mitochondrial membrane potential. However, the activity of mitochondrial complex I NADH dehydrogenase was not affected by ketamine. This study shows that a clinically relevant concentration of ketamine (100 microM) can suppress macrophage function of phagocytosis, its oxidative ability, and inflammatory cytokine production possibly via reduction of the mitochondrial membrane potential instead of direct cellular toxicity.
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PMID:Suppressive effects of ketamine on macrophage functions. 1578 Dec 91

This study was designed to investigate the effects of inducible nitric oxide synthase (iNOS) inhibition with S-methylisothiourea (SMT) and L-N-(1-iminoethyl)-lysine (L-Nil) on the endotoxemia induced by intravenous lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure (AP), heart rate (HR), WBC, platelets, plasma nitrite/nitrate, tumor necrosis factor alpha (TNF alpha), and biochemical factors were measured for 24 hours after LPS with or without iNOS inhibitors. RT-PCR was employed to determine the iNOS and endothelial NOS (eNOS) mRNA. Pathologic examinations of the liver and heart were performed. SMT and L-Nil improved the systemic hypotension and increased the HR after LPS. These agents attenuated the LPS-induced leukocytopenia and thrombocytopenia and the increase in nitrite/nitrate. However, iNOS inhibition aggravated the LPS-induced changes in TNF alpha, all biochemical factors, and the hepatic and cardiac tissue damage. The iNOS mRNA, but not the eNOS, was reduced. Our results in conscious rats indicate that iNOS inhibition enhances the organ dysfunction and tissue damage in sepsis. The discrepancy may be attributed to the method for evaluating the sepsis and the effects of anesthesia. Further investigation is required to ensure the effects of iNOS inhibition on sepsis before iNOS inhibitors can be applied in clinical cases with sepsis.
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PMID:Inducible nitric oxide synthase inhibition potentiates multiple organ dysfunction induced by endotoxin in conscious rats. 1582 34

BACKGROUND: The possibility exists for major complications to occur when individuals are intoxicated with alcohol prior to anesthetization. Halothane is an anesthetic that can be metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which reacts with endogenous proteins to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct which is formed by acetaldehyde (AA) and malondialdehyde reacting with endogenous proteins, has been found in both patients and animals chronically consuming alcohol. These TFA and MAA-adducts have been shown to cause the release of inflammatory products by various cell types. If both adducts share a similar mechanism of cell activation, receiving halothane anesthesia while intoxicated with alcohol could exacerbate the inflammatory response and lead to cardiovascular injury. METHODS: We have recently demonstrated that the MAA-adduct induces tumor necrosis factor-alpha (TNF-alpha) release by heart endothelial cells (HECs). In this study, pair and alcohol-fed rats were randomized to receive halothane pretreatments intra peritoneal. Following the pretreatments, the intact heart was removed, HECs were isolated and stimulated with unmodified bovine serum albumin (Alb), MAA-modified Alb (MAA-Alb), Hexyl-MAA, or lipopolysaccharide (LPS), and supernatant concentrations of TNF-alpha were measured by ELISA. RESULTS: Halothane pre-treated rat HECs released significantly greater TNF-alpha concentration following MAA-adduct and LPS stimulation than the non-halothane pre-treated in both pair and alcohol-fed rats, but was significantly greater in the alcohol-fed rats. CONCLUSION: These results demonstrate that halothane and MAA-adduct pre-treatment increases the inflammatory response (TNF-alpha release). Also, these results suggest that halothane exposure may increase the risk of alcohol-induced heart injury, since halothane pre-treatment potentiates the HEC TNF-alpha release measured following both MAA-Alb and LPS stimulation.
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PMID:Halothane potentiates the alcohol-adduct induced TNF-alpha release in heart endothelial cells. 1582 1

Heat shock proteins (HSPs) represent a group of highly conserved intracellular proteins that participate in protective adaptation against cellular stress. We evaluated the neuroprotective role of the 70-kDa HSP (HSP70) and the 90-kDa HSP (HSP90) at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, during fatal endotoxemia. In Sprague-Dawley rats maintained under propofol anesthesia, Escherichia coli lipopolysaccharide (30 mg/kg, i.v.) induced a decrease (phase I), followed by an increase (phase II; "pro-life" phase) and a secondary decrease (phase III; "pro-death" phase) in the power density of the vasomotor component of systemic arterial pressure spectrum, along with progressive hypotension or bradycardia. Proteomic and Western blot analyses revealed that whereas HSP70 expression in the RVLM was significantly augmented during phases I and II and returned to baseline during phase III endotoxemia, HSP90 protein expression remained constant. The increase in HSP70 level was significantly blunted on pretreatment with microinjection of the transcription inhibitor actinomycin D or protein synthesis inhibitor cycloheximide into the bilateral RVLM. Functional blockade of HSP70 in the RVLM by an anti-HSP70 antiserum or prevention of synthesis by an antisense hsp70 oligonucleotide exacerbated mortality or potentiated the cardiovascular depression during experimental endotoxemia, alongside significantly reduced nitric-oxide synthase (NOS) I or protein kinase G (PKG) level or augmented NOS II or peroxynitrite level in the RVLM. We conclude that whereas HSP90 is ineffective, de novo synthesis of HSP70 in the RVLM may confer neuroprotection during fatal endotoxemia by preventing cardiovascular depression via enhancing the sympathoexcitatory NOS I/PKG signaling pathway and inhibiting the sympathoinhibitory NOS II/peroxynitrite cascade in the RVLM.
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PMID:In the rostral ventrolateral medulla, the 70-kDa heat shock protein (HSP70), but not HSP90, confers neuroprotection against fatal endotoxemia via augmentation of nitric-oxide synthase I (NOS I)/protein kinase G signaling pathway and inhibition of NOS II/peroxynitrite cascade. 1582 95

We have previously observed an increase in nitric oxide (NO) content in rat brain cortex following halothane, sevoflurane or isoflurane anaesthesia. This study was undertaken in order to determine whether isoform-specific nitric oxide synthase (NOS) inhibitors and inducers could modify these increases in NO contents. Rats were subjected to isoflurane and sevoflurane anaesthesia with concomitant administration of neuronal nitric oxide synthase (nNOS) inhibitor 7-Nitro-indazole (7-NI), inducible nitric oxide synthase (iNOS) inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) or lipopolysaccharide. NO concentration in different organs was measured by electron paramagnetic resonance (EPR) spectroscopy. 7-NI significantly decreased NO concentration in cerebellum but not in brain cortex, whereas AMT decreased NO in all the organs studied. Anaesthesia significantly increased NO concentration in brain cortex and decreased that in cerebellum. AMT abolished the NO increase in brain cortex. Anaesthesia enhanced the drastic increase in NO concentration in brain cortex after intraventricular lipopolysaccharide administration. Isoflurane was found to inhibit recombinant nNOS and iNOS activities at high concentrations (EC50=20 mM). Our data suggest a putative role for iNOS in the increase in NO levels produced by isoflurane and sevoflurane, whereas nNOS activity is probably inhibited during anaesthesia.
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PMID:Putative role of nitric oxide synthase isoforms in the changes of nitric oxide concentration in rat brain cortex and cerebellum following sevoflurane and isoflurane anaesthesia. 1586 1

Cardiopulmonary bypass (CPB) is associated with an inflammatory process that leads to lung injury. In this study, we hypothesized that inhaled nitric oxide (INO) possesses the ability to modulate CPB-induced inflammation. Fifteen male pigs were randomly divided into 3 groups: Sham, CPB+LPS (CPB and lipopolysaccharide), and CPB+LPS+INO. INO (20 parts per million) was administered for 24 h after anesthesia. CPB was performed for 90 min, and LPS was infused (1 microg/kg) after CPB. Bronchoalveolar lavage (BAL) fluid and blood were collected at T0 (before CPB), at 4 h, and at 24 h. At 24 h, BAL interleukin-8 (IL-8) levels were not increased as expected in the CPB+LPS group compared with the Sham group, but they were reduced significantly in the CPB+LPS+INO group. Cell hypo reactivity observed in the groups receiving LPS also seemed to downregulate endothelial nitric oxide synthase NOS protein expression relative to the Sham group. Nitrite and nitrate (NOx) concentrations were decreased significantly in the groups without INO. Moreover, animals treated with INO showed higher rates of pulmonary apoptosis compared with their respective controls. These results demonstrate that NOx production is reduced after CPB and that INO acts on the inflammatory process by diminishing neutrophils and their major chemoattractant, IL-8. INO also increases cell apoptosis in the lungs under inflammatory conditions, which may explain, in part, how it resolves pulmonary inflammation.
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PMID:The anti-inflammatory effect of inhaled nitric oxide on pulmonary inflammation in a swine model. 1587 Aug 39


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