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)

In the present study, some new amides of 5-amino-3-methylisoxazole-4-carboxylic acid were obtained. All new structures possessed markedly different groups of electron acceptor character, different spatial structure and they contained nitrogen heteroatom, enabling formation of salts and, at the same time, higher biological availability. They were examined for immunomodulating activity in comparison with cyclosporine A (CsA). We investigated effects of the compounds on the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by human peripheral blood cells. Some compounds exhibited suppressory action which corresponded with increasing electronoacceptor nature of the amide substituent. Two compounds, characterized by flat aromatic rings, demonstrated quite different properties. Much higher activity was expressed by compounds which contained -NH group, the group which conditioned immunostimulatory activity in other compounds described previously.
Pol J Pharmacol
PMID:Immunological activity of new heterocyclic amides of 5-amino-3-methylisoxazole-4-carboxylic acid. 1060 40

Chemical composition of lipopolysaccharide (LPS) isolated from an effective (97) and ineffective (87) strains of R. l. viciae has been determined. LPS preparations from the two strains contained: glucose, galactose, mannose, fucose, arabinose, heptose, glucosamine, galactosamine, quinovosamine, and 3-N-methyl-3,6-dideoxyhexose, as well as glucuronic, galacturonic and 3-deoxyoctulosonic acid. The following fatty acids were identified: 3-OH 14:0, 3-OH 15:0, 3-OH 16:0, 3-OH 18:0 and 27-OH 28:0. The ratio of 3-OH 14:0 to other major fatty acids in LPS 87 was higher that in LPS 97. SDS/PAGE profiles of LPS indicated that, in lipopolysaccharides, relative content of S form LPS I to that of lower molecular mass (LPS II) was much higher in the effective strain 97 than in 87. All types of polysaccharides exo-, capsular-, lipo, (EPS, CPS, LPS, respectively) examined possessed the ability to bind faba bean lectin. The degree of affinity of the host lectin to LPS 87 was half that to LPS 97. Fatty acids (FA) composition from bacteroids and peribacteroid membrane (PBM) was determined. Palmitic, stearic and hexadecenoic acids were common components found in both strains. There was a high content of unsaturated fatty acids in bacteroids as well as in PBM lipids. The unsaturation index in the PBM formed by strain 87 was lower than in the case of strain 97. Higher ratio of 16:0 to 18:1 fatty acids was characteristic for PMB of the ineffective strain.
Acta Biochim Pol 1999
PMID:Chemical characterization of effective and ineffective strains of Rhizobium leguminosarum bv. viciae. 1082 71

Heme oxygenase-1 (HO-1), an inducible enzyme degrading heme to biliverdin, iron and carbon monoxide, is involved in regulation of inflammation and angiogenesis. Tin protoporphyrin (SnPPIX) and zinc protoporphyrin (ZnPPIX) are commonly used as competitive inhibitors of HO-1. We aimed to compare the effects of SnPPIX and ZnPPIX on the production of vascular endothelial growth factor (VEGF), activity of inducible nitric oxide synthase (iNOS) and cell viability. All experiments were performed on rat vascular smooth muscle cells and murine RAW264.7 macrophages treated with 3-10 microM protoporphyrins. Some cells were additionally stimulated with IL-1beta or with lipopolysaccharide. After a 24 h incubation period SnPPIX and ZnPPIX significantly reduced the generation of VEGF in vascular smooth muscle cells and RAW264.7, both in resting and stimulated cells. The inhibitory potentials of both protoporphyrins on VEGF synthesis were very similar. In contrast, analysis of iNOS activity revealed that results obtained with different HO-1 inhibitors are discrepant. Generation of nitric oxide by iNOS was significantly increased by SnPPIX but strongly decreased by ZnPPIX. Similar differences were observed when cell viability was compared. SnPPIX improved the cell survival rate, whereas the same doses of ZnPPIX exerted some cytotoxic effects. In summary, SnPPIX and ZnPPIX can be used as HO-1 inhibitors in some experimental models. However, these compounds produce also HO-independent effects, which can make the interpretation of experiments very uncertain. Thus the involvement of the HO-1 pathway should be always confirmed by more specific methods.
Acta Biochim Pol 2003
PMID:Effects of protoporphyrins on production of nitric oxide and expression of vascular endothelial growth factor in vascular smooth muscle cells and macrophages. 1267 48

Depression is associated with abnormal functions of the immune system. In this study, we investigated how two modem antidepressant therapies, chronic treatment with transcranial magnetic stimulation (TMS) and administration of an antidepressant belonging to selective serotonin reuptake inhibitors (SSRI), paroxetine, affect the proliferative response of thymocytes and splenocytes stimulated in vitro with various mitogens. Paroxetine (10 mg/kg) and TMS (B = 1.2 T, f = 30 Hz, t = 330 s) were applied once daily for 12 consecutive days, while, if given jointly paroxetine was injected 30 min before TMS. The mitogens used were: concanavalin A (Con A), pokeweed mitogen (PWM) or lipopolysaccharide (LPS). While either treatment applied alone had no effect on proliferative response, the joint application of paroxetine and TMS significantly depressed it. The literature data suggest that pulsed magnetic field may directly inhibit mitogen-activated lymphocyte proliferation, which is also inhibited by the presence of high level of serotonin. The present results suggest that both effects are additive, and because of that application of both treatments, whose effects alone are insufficient to prompt the reaction, possibly because adaptive changes during chronic treatment, results in a significant inhibition of lymphocyte proliferation.
Pol J Pharmacol
PMID:Effect of combined treatment with paroxetine and transcranial magnetic stimulation (TMS) on the mitogen-induced proliferative response of rat lymphocytes. 1286 18

The study examined the effect of some typical and atypical antipsychotic drugs on mouse lymphocyte metabolic and proliferative activity in vitro. The typical antipsychotic drug chlorpromazine (3 x 10(-6), 10(-5) and 10(-4) M), significantly inhibited 3H-thymidine incorporation into C57BL/6 mouse spleen cells stimulated by concanavalin A (Con A), lipopolysaccharide (LPS) or pokeweed mitogen (PWM). Chlorpromazine at concentrations of 10(-5) and 10(-4) M also suppressed the metabolic activity of splenocytes after Con A stimulation. The atypical antipsychotic agent clozapine (10(-4) and 10(-5) M) decreased the proliferative activity of splenocytes after LPS stimulation, but its inhibitory effect after Con A was observed only at higher concentrations. On the other hand, clozapine did not affect the metabolic activity of splenocytes. Sulpiride, a selective dopamine D2 antagonist, at concentrations ranging from 10(-8) to 10(-4) M had no inhibitory effect on the proliferative or metabolic activity of the tested cells. The obtained results indicate that of the three antipsychotic drugs studied, chlorpromazine shows the most potent immunosuppressive effect, clozapine produces a moderate effect and sulpiride is totally inactive. These findings suggest that the choice of antipsychotic drugs should also depend on disturbance of immune system activity, in particular, those occurring in the several forms of psychosis.
Pol J Pharmacol
PMID:Effect of some antipsychotic drugs on immunoreactivity in C57BL/6 mice. 1286 35

Shigella flexneri rods play an important role in human intestinal infections. In the presented studies we have shown that O-acetyl and glucose residues, substituted in main GalNAc-Rha chains of lipopolysaccharide (LPS) are important for the bactericidal effect of human serum. By dot-blot, immunoblotting and ELISA with immobilized LPS we have shown correlation of C3 fragments deposition and serum resistance. LPSs isolated from a serum-sensitive strain deposited more C3 fragments than LPSs from serum-resistant Shigella flexneri strains.
Acta Microbiol Pol 2003
PMID:The factor C3 conversion in human complement by smooth Shigella flexneri lipopolysaccharides. 1291 27

Major depression is accompanied by an activation of the inflammatory response system (IRS) and antidepressants may have immunoregulatory activities. This study was carried out to compare the effect of imipramine, mianserin and lithium on the in vitro production of Th1-like cytokines, such as IL-2, IFN-gamma, lymphotoxin and Th2-like cytokines such as IL-4, IL-10 as well as IL-12 and TGF-beta. Peripheral blood mononuclear cells (PBMC) of 16 healthy volunteers were stimulated with polyclonal activators (phytohemagglutinin with lipopolysaccharide PHA + LPS) with or without incubation with imipramine, mianserin (1 microM) or lithium (1 mM). Imipramine and mianserin exhibited similar activities enhancing unstimulated IFN-gamma and IL-10 production. In PHA + LPS-stimulated PBMC both antidepressants inhibited IFN-gamma, IL-2 and lymphotoxin production (Th1-like cytokines) as well as IL-12 and IL-4 production. Under the same in vitro conditions, both antidepressants stimulated production of negative immunoregulatory cytokines such as IL-10 and TGF-beta. Lithium differed significantly from imipramine and mianserin, as it enhanced IL-2, IFN-gamma, IL-10 and TGF-beta production and inhibited only IL-4. All three examined antidepressants reduced IFN-gamma/IL-10 ratio. None of the antidepressants at the used concentrations induced apoptosis in PBMC so those changes in cytokine production were not the result of selective killing of certain cell subpopulations. Imipramine and mianserin at high concentrations negatively influenced reactive oxygen species (ROS) production in neutrophils, however, at concentrations in the therapeutical range none of the antidepressants used influenced "oxidative burst" in neutrophils. The results indicate that antidepressants exert immunoregulatory effects on human leukocyte functions, especially on cytokine production.
Pol J Pharmacol
PMID:In vitro immunoregulatory effects of antidepressants in healthy volunteers. 1450 14

Ferrous-diethyldithiocarbamate (Fe(DETC)(2)) chelate is a lipophilic spin trap developed for (.)NO detection by electron paramagnetic resonance (EPR) spectroscopy. Using this spin trap we investigated the kinetics of (.)NO production in endotoxaemia in rats induced by lipopolysaccharide (Escherichia coli, 10 mg/kg). The NO-Fe(DETC)(2) complex was found to give a characteristic EPR signal, and the amplitude of the 3rd (high-field) component of its hyperfine splitting was used to monitor the level of (.)NO. We found that in blood, kidney, liver, heart and lung (.)NO production starts to increase as early as 2 h after LPS injection, reaches the maximum 6 h after LPS injection and then returns to basal level within further 12-18 h. Interestingly, in the eye bulb the maximum of (.)NO production was detected 12 h after LPS, and the signal was still pronounced 24 h after LPS. In brief, the highly lipophilic exogenous spin trap, Fe(DETC)(2) is well suited for assessment of (.)NO production in endotoxaemia. We demonstrated that the kinetics of increased production of (.)NO in endotoxaemic organs, with the notable exception of the eye, do not follow the known pattern of NOS-2 induction under those conditions. Accordingly, only in early endotoxaemia a high level of (.)NO is detected, while in late endotoxaemia (.)NO detectability is diminished most probably due to concomitant oxidant stress.
Acta Biochim Pol 2003
PMID:Kinetics of increased generation of (.)NO in endotoxaemic rats as measured by EPR. 1451 61

Previously, we have found that some antipsychotic drugs are able to inhibit glucocorticoid receptor (GR)-mediated gene transcription. Since these drugs are known not only to inhibit hypothalamic-pituitary-adrenal (HPA) axis activity, but also to modulate the immunological system, the aim of the present study was to compare the effect of sulpiride and clozapine on GR function under basal culture conditions and during activation by lipopolysaccharide (LPS). The effect of clozapine and sulpiride alone and with LPS, the immune system activator, on glucocorticoid-mediated gene transcription was investigated in fibroblast cells, stably transfected with a mouse mammary tumor virus--chloramphenicol acetyltransferase plasmid (LMCAT cells). Treatment of the cells with clozapine (3-10 microM) for 2 days significantly and in concentration-dependent manner decreased the chloramphenicol acetyltransferase (CAT) activity, while sulpiride (1, 3, 5 and 10 microM) was without any effect. LPS (1 microg/ml) given alone inhibited the corticosterone-induced gene transcription by ca. 35%. Clozapine (3, 5 and 10 microM) inhibited the effect of LPS (1 microM), while sulpiride, which alone had no effect on GR function, enhanced LPS (1 microM) action. The obtained results indicate that inhibition of GR-mediated gene transcription by LPS and clozapine can be a mechanism by which these compounds blocked some effects induced by glucocorticoids. Opposite effect of clozapine and sulpiride on LPS action may result from their distinct effect on activity of some kinases involved in regulation of GR transcriptional function and may determine their utility in the treatment of schizophrenia with or without immune system activation.
Pol J Pharmacol
PMID:Opposite effects of clozapine and sulpiride on the lipopolysaccharide-induced inhibition of the GR-mediated gene transcription in fibroblast cells. 1473 Jan 15

The inducible nitric oxide synthase (iNOS) plays an important role in endotoxic shock. However,little is known about the involvment of constitutive isoform(s) of NOS (cNOS). The aim of this study was to determine the role of cNOS in the mouse brain after lipopolysaccharide (LPS) injection. Concentrations of nicotinamide adenine dinucleotide (NAD(+)), carbonyl group and thiobarbituric acid reactive substances were determined spectrophotometrically, cNOS mRNA was evaluated by RT-PCR. Our data showed that LPS significantly decreased NAD(+) level, and enhanced protein and lipid oxidation, but had no effect on cNOS mRNA expression. Inhibitors of cNOS protected the cells against alterations evoked by LPS, suggesting involvement of cNOS isoforms in pathology.
Pol J Pharmacol
PMID:Inhibition of nitric oxide synthase prevents energy failure and oxidative damage evoked in the brain by lipopolysaccharide. 1559 55


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