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)

We studied the effects of nutrients such as vitamin C, E, B6, niacin, and methionine on the blastogenic response of splenocytes and lipid peroxidation (LPO) in lung and liver of mice exposed to SiO2 dust. The results showed that after treatment with SiO2, the blastogenic response of splenocytes decreased significantly (p < 0.001), whereas the LPO level in lung and liver increased remarkably (lung p < 0.05; liver p < 0.001). Vitamin E, C, and niacin strongly enhanced the blastogenic response of T and B splenic lymphocytes to concanavalin-A and to lipopolysaccharide (p < 0.001). The effects of methionine and B6 were much less intense. Other supplied nutrients have been shown to inhibit LPO in lung and liver of mice exposed to SiO2 (p < 0.001).
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PMID:Effects of vitamins and methionine on blastogenic response of splenocytes and lipid peroxidation in lung and liver of mice exposed to SiO2 dust. 772 88

The regulatory effect of endogenously synthesized eicosanoid metabolites on the expression of tissue inhibitor of metalloproteinases (TIMP), interstitial collagenase, and 92-kDa gelatinase by human macrophages was examined. TIMP and metalloproteinase production were stimulated with three agonists that produce distinct patterns of eicosanoid synthesis: lipopolysaccharide (10 micrograms/ml), denatured collagen (10 micrograms/ml), or zymosan (1 mg/ml). Indomethacin (3 micrograms/ml) or MK886 (3 microM), a specific inhibitor of 5-lipoxygenase, was used to examine the role of endogenous metabolites of arachidonic acid. Regardless of the agonist used, TIMP production by macrophages was inhibited 65% by indomethacin, synthesis of interstitial collagenase was reduced 70%, and expression of 92-kDa gelatinase was decreased 40%. In contrast, inhibition of leukotriene synthesis had no effect on metalloproteinase or TIMP production. The agonist-stimulated increase in TIMP and collagenase production was directly correlated to the cumulative prostaglandin E2 level induced by the agonist used. However, if response to an agonist was poor, the exogenous addition of prostaglandin E2 could not increase TIMP or collagenase production more than twofold, indicating an important permissive effect of the agonist on the regulation of each protein's expression. The mechanism of indomethacin inhibition of TIMP and collagenase production was studied by labeling the cells with [35S]-methionine and performing immunoprecipitation using specific antiserum. Indomethacin markedly inhibited the lipopolysaccharide-induced biosynthesis of both TIMP and collagenase. Northern analysis revealed parallel suppression of TIMP and collagenase steady-state mRNA levels by indomethacin, indicating pretranslational control. The regulation of inflammatory-cell TIMP and interstitial collagenase expression by prostaglandin E2 suggests that therapy inhibiting the cellular response to prostaglandins may be useful in cutaneous and systemic disease states involving macrophage-mediated connective-tissue destruction.
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PMID:Agonist-induced expression of tissue inhibitor of metalloproteinases and metalloproteinases by human macrophages is regulated by endogenous prostaglandin E2 synthesis. 779 41

We investigated the effect of several opioid peptides on the activation of murine peritoneal exudate macrophages (M phi) in vitro. M phi were treated with interferon (IFN) as a priming agent and bacterial lipopolysaccharide (LPS) as a triggering agent in the presence or absence of opioid peptides. M phi activation was assessed by their tumoricidal activity. When treatment with IFN and LPS resulted in a high level activation of M phi, dynorphin-A exerted no further enhancing effect. When treatment induced only weak activation, however, dynorphin-A augmented the M phi activation. Leucine-enkephalin, methionine-enkephalin, and also beta-endorphin had augmenting effects. An opioid receptor antagonist, naloxone, reduced the effect of dynorphin-A and beta-endorphin. When M phi were treated sequentially with IFN and LPS, beta-endorphin operated in combination with LPS only. Moreover, beta-endorphin was effective for already activated M phi. These results indicate that opioid peptides act on M phi via classical opioid receptors, and that responsiveness to opioid peptides is induced in the triggering stage of M phi activation.
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PMID:Augmenting effect of opioid peptides on murine macrophage activation. 790 88

In the present study, we have examined the effect of opioid peptide methionine enkephalin (MENK) on production of factors with interleukin-1 (IL-1) and tumor necrosis factor (TNF) activity by mouse peritoneal macrophages and assessed whether modification in the production of those cytokines could be related to alteration of phagocytosis by MENK. None of the MENK concentrations examined altered IL-1 or TNF activity alone. However, peritoneal macrophages co-stimulated with 1 microgram of lipopolysaccharide (LPS) and 10(-10) M MENK potentiated IL-1 activity, compared to LPS alone, but abrogated TNF activity induced by LPS. While MENK alone slightly decreased phagocytosis of sheep red blood cells (SRBC) by mouse peritoneal macrophages, cells simultaneously incubated with 1 microgram of LPS and 10(-10) M MENK had increased phagocytosis compared to LPS alone. Moreover, phagocytosis of SRBC by cells incubated overnight with the supernatant of the respective cell culture was significantly augmented. These results provide additional evidence for the immunoregulatory role of neuropeptides and suggest that the modulatory action of MENK could be mediated, at least in part, through the up-regulation of cytokines, most probably IL-1 and TNF.
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PMID:Modulation of lipopolysaccharide-induced production of cytokines by methionine-enkephalin. 792 13

Secretory leukocyte protease inhibitor (SLPI) is a potent proteinase inhibitor produced in the lung. Stimulated neutrophils at sites of inflammation can inactivate SLPI by myeloperoxidase-mediated oxidation of the methionine residue in the active site of SLPI. Apocynin is a selective inhibitor of NADPH oxidase and may therefore protect SLPI against neutrophil-mediated oxidative inactivation. The aim of the present study was to determine the effect of apocynin on the efficacy of SLPI in preventing experimental emphysema. To investigate the effect of apocynin on emphysema without SLPI treatment, three groups of eight hamsters each received drinking water containing apocynin at concentrations of 2, 20, and 200 micrograms/ml, respectively. Emphysema was induced in these hamsters by intratracheal instillations of 500 micrograms of lipopolysaccharide (LPS) twice a week for 4 wk. In hamsters that received 200 micrograms/ml apocynin, the development of emphysema was reduced by 26.2% (p = 0.01). Other apocynin concentrations had no effect. The experiment was repeated, with SLPI added to the treatment. Of a total of six groups of hamsters, four groups (three with apocynin and one with solvent) received twice-weekly doses of a mixture of 500 micrograms of LPS and 1 mg SLPI in 200 microliters saline in the trachea for 4 wk. In addition, each LPS instillation was followed 24 and 48 h later by an instillation containing 1 mg of SLPI. Apocynin (20 and 200 micrograms/ml) improved the protective effect of SLPI from 37 to 64% and 79%, respectively (p < 0.01). We conclude that oral administration of apocynin can improve the efficacy of SLPI in preventing LPS-induced emphysema.
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PMID:Apocynin improves the efficacy of secretory leukocyte protease inhibitor in experimental emphysema. 795 25

Injury results in altered hepatocyte protein synthesis including the production of acute-phase reactants. Evidence suggests that these hepatocyte products regulate macrophage function; however, their role in liver macrophage-mediated hepatocyte dysfunction following a second insult is poorly characterized. We hypothesize that IL-6-stimulated hepatocyte products alter liver macrophage responses to lipopolysaccharide, contributing to enhanced hepatocyte dysfunction. To test this hypothesis, hepatocytes, obtained by liver collagenase digestion, were treated with rIL-6 (murine, 300 units/ml) for 24 hr, and then liver macrophages, obtained by perfusion and pronase digestion, were added to establish cocultures. Cocultures were then stimulated with endotoxin (LPS, Escherichia coli O111:B4, 10 micrograms/ml) and hepatocyte dysfunction was assessed by determining secretory protein synthesis ([35S]methionine labeling, trichloracetic acid precipitation, and SDS-PAGE) and energy metabolism [mitochondrial respiration using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) dye]. Cultures of hepatocytes alone stimulated with IL-6, LPS, or sequential IL-6 followed by LPS demonstrate no difference in total secretory protein synthesis or mitochondrial respiration. In contrast, hepatocyte-liver macrophage cocultures demonstrate significantly reduced total secretory protein synthesis following sequential IL-6 followed by LPS ([35S]methionine cpm x 10(3): control, 33.8 +/- 8.5; LPS, 25.8 +/- 6.3; IL-6/LPS, 15.7 +/- 6.4; P < 0.05 vs control). This effect is specific to IL-6 since sequential TNF-alpha followed by LPS did not result in significant suppression of secretory protein synthesis. One-dimensional SDS-PAGE of labeled coculture secretory proteins demonstrates qualitative changes following sequential insult in vitro compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sequential insult enhances liver macrophage-signaled hepatocyte dysfunction. 804 Nov 36

Secretory leukocyte inhibitor (SLPI) is a potent inhibitor of serine proteinases, but sensitive to oxidative inactivation due to a methionine residue in the active centre of the inhibitor. We compared the potency of an oxidation-resistant mutant of recombinant SLPI with native recombinant SLPI in lipopolysaccharide (LPS)-induced emphysema in the hamster. Application of this oxidation-resistant mutant reduced the induced emphysema by 70 and 85% in two separate series of experiments. In contrast, an equal amount of native rSLPI resulted in significantly lower inhibition, 30 and 23%, respectively (P = 0.002). To demonstrate the effect of oxygen radicals upon a single LPS instillation in the lungs, we measured anti-neutrophil elastase activity in lung lavage fluid at 10 and 24 h after the instillation of a mixture of LPS and native rSLPI. We found that residual native rSLPI was only 70 and 55% active, respectively. The rSLPI-mutant remained 93% active in a similar experiment. The native and mutant inhibitor showed equal potency against proteinases in a granule extract of hamster neutrophils. We conclude that the replacement of methionine by leucine in the inhibitory centre of rSLPI results in a decreased sensitivity to oxidative inactivation and that this alone is sufficient to explain the greater efficiency of the rSLPI-mutant in reducing the extent of LPS-induced emphysema.
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PMID:Potency of an oxidation-resistant mutant of secretory leukocyte proteinase inhibitor in lipopolysaccharide-induced emphysema in hamsters. 809 18

Antipyretic properties have been ascribed to arginine vasopressin (AVP), and the site where its antipyretic effects are mediated in the brain was identified as the ventrolateral septum of the limbic system. In guinea pigs, the majority of AVP projections to the septum originate from parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). Electrical stimulation of the PVN with 10-s trains of current pulses (duration 1 ms, frequency 20 Hz, amplitude 8 V, current 0.205 +/- 0.017 mA) reduced the febrile response to an intramuscular injection of 20 micrograms/kg lipopolysaccharide (LPS from Escherichia coli, 0111: B4) by 54% compared with unstimulated animals. This reduction in fever by electrical PVN stimulation was partly reversed by a simultaneous intraseptal microinfusion of the vasopressinergic V1-receptor antagonist d(CH2)5[Tyr(Met)2]AVP at a concentration of 10(-5) mol for 6 h with an infusion speed of 0.1 microliter/min. We further investigated the effects of intraseptal microinfusions or systemic infusions of the gamma-melanocyte-stimulating hormone (gamma-MSH), a derivative of the proopiomelanocortin, on LPS-induced fever. Intraseptal microinfusions of gamma-MSH at a concentration of 10(-5) mol/l for 6 h with an infusion speed of 0.1 microliter/min caused a 38% reduction in fever. A significantly greater 57% reduction in fever was observed when the intraseptal microinfusion of gamma-MSH was combined with electrical stimulation of the PVN (for parameters see above). A systemic infusion of 0.261 mumol gamma-MSH for 6 h reduced LPS fever to approximately 50% compared with animals infused with vehicle (0.9% saline).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antipyresis caused by stimulation of vasopressinergic neurons and intraseptal or systemic infusions of gamma-MSH. 814 22

The purpose of this study was to determine the most potent activator of the respiratory burst of polymorphonuclear leukocytes (PMN) with respect to the oxidative modification of low density lipoprotein (LDL). Phorbol-12-myristate-13-acetate (PMA), n-formyl-methionyl-leucylphenylalanine (nFMLP), lipopolysaccharide (LPS), and opsonized zymosan (OZ) were tested. The generation of reactive oxygen species by PMN was assayed as superoxide anion production. Oxidative modification of LDL was monitored by thiobarbituric acid reactive substance (TBARS) activity, by conjugated dienes formation at 234nm and by electrophoretic mobility on agarose gel. PMA was the most potent activator of PMN, inducing a 6-fold increase in the superoxide anion production, followed by OZ (3-fold increase). PMA activation also induced the greatest modification of LDL by PMN: 700% increase of conjugated dienes formation, 222% increase of TBARS, and 70% increase in the electrophoretic mobility. The indices of oxidative modification significantly correlated with the superoxide anion generated by different activators. Also, LDL oxidation by PMN was inhibited by superoxide dismutase but not by catalase, methionine, or hydroxyl radical scavengers. Our data indicate that PMNs activated by PMA produce a mildly oxidized form of LDL by a mechanism that appears to involve the superoxide anion.
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PMID:LDL modification by activated polymorphonuclear leukocytes: a cellular model of mild oxidative stress. 829 96

Quinolinic acid (QUIN) may act.as an excitotoxin when it is abundant in the brain. We have shown previously that the activity of 3-hydroxyanthranilate 3,4-dioxygenase, a QUIN-synthesizing enzyme, was abnormally high in the brains of epilepsy-prone E1 mice as compared with that of ddY mice. Here, we estimated the QUIN contents in the brains of these mice. The results showed that the basal QUIN content in the cerebral cortex of E1 mice was twice as high as that of ddY mice. Systemic injection of 400 mumol/kg body weight of L-tryptophan (L-Trp) increased the cortical levels of QUIN in both E1 mice and ddY mice by 189% and 118%, respectively. Administration of 400 mumol/kg each of L-threonine and D,L-methionine had no appreciable effect on the L-Trp-caused increase in the cortical QUIN levels. Co-administration of 5-fluorotryptophan or 5-methyltryptophan, tryptophan analogs, with L-Trp did not reduce but rather enhanced the cortical QUIN levels (by 18% and 92%, respectively). No significant change in the cortical QUIN concentrations was observed with injection of 2 mg/kg body weight of E. coli lipopolysaccharide (LPS) in E1 mice. However, injection of L-Trp in the LPS-treated E1 mice produced a more marked increase in the cortical QUIN levels than that injected with L-Trp alone. These results suggest that the brain QUIN contents of E1 mice are dependent not only on the activity of QUIN-synthesizing enzyme but also on the rate of flux of its substrate, L-Trp or its metabolite(s), in the brain.
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PMID:High levels of quinolinic acid in brain of epilepsy-prone E1 mice. 837 78


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