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)

Prostaglandin E2 (PGE2) and macrophage (Mphi)-derived reactive nitrogen intermediates (RNI) have been implicated in T cell dysfunction after thermal injury. Normally, Mphi inducible nitric oxide synthase (iNOS) activity can be regulated by PGE2, however, it is unknown whether PGE2 modulates Mphi iNOS activity after thermal injury. Splenic Mphi isolated from mice 7 days after thermal injury produced higher levels of RNI than Mphi from sham mice when stimulated with lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in combination. PGE2, when added concurrently with LPS, suppressed RNI production by Mphi from sham mice, whereas Mphi from injured mice were unaffected. When Mphi were pretreated with PGE2 before LPS, RNI production was suppressed in both populations. RNI production in response to IFN-gamma or IFN-gamma and TNF-alpha in combination was enhanced by PGE2 in both populations, however, the effect was markedly greater in Mphi from injured mice. The PGE2-mediated changes in RNI production were paralleled by similar changes in iNOS protein expression, suggesting that the effect of PGE2 was at the level of enzyme expression rather than activity. Dibutryl cAMP induced similar effects as PGE2, suggesting the response to PGE2 after thermal injury is independent of potential changes in PGE2-induced adenylate cyclase activity and is cAMP-mediated. The results indicate that Mphi from burned mice display an altered sensitivity to PGE2, resulting in enhanced iNOS activity. Thus, PGE2, which is elevated after thermal injury and can directly suppress T cell function, may also contribute to immune dysfunction through the enhancement of Mphi iNOS activity.
 ...
PMID:Thermal injury alters macrophage responses to prostaglandin E2: contribution to the enhancement of inducible nitric oxide synthase activity. 985 Jan 55

The aim of the study reported here was to investigate the production of Bordetella pertussis outer membrane vesicles (OMVs). Numerous vesicles released from cells grown in Stainer-Scholte liquid medium were observed. The formation of similar vesicle-like structures could also be artificially induced by sonication of concentrated bacterial suspensions. Immunoblot analysis showed that OMVs contain adenylate cyclase-hemolysin (AC-Hly), among other polypeptides, as well as the lipopolysaccharide (LPS). Experiments carried out employing purified AC-Hly and OMVs isolated from B. pertussis AC-Hly- showed that AC-Hly is an integral component of the vesicles. OMVs reported here contain several protective immunogens and might be considered a possible basic material for the development of acellular pertussis vaccines.
 ...
PMID:Release of outer membrane vesicles from Bordetella pertussis. 1035 15

Lung tissue may be an important source of systemic inflammation associated with sepsis and the acute respiratory distress syndrome (ARDS). An ex vivo model of freshly explanted lung tissue in culture was developed to evaluate the ability of lipopolysaccharide (LPS) to directly stimulate lung tissues under conditions where indirect mechanisms such as recruitment of blood-derived inflammatory cells could not be implicated. Under control conditions, lung explants produced a high level of macrophage inflammatory protein-2 (MIP-2). Eight hours after LPS challenge, there were marked increases in the production of tumor necrosis factor-alpha (TNF-alpha) from 0.18 +/- 0.04 to 4.13 +/- 0.23 ng/ml/g tissue (p < 0.05), MIP-2 from 60.0 +/- 7.4 to 165.6 +/- 10.3 ng/ml/g tissue (p < 0.05), and tissue lipid peroxidation (malonaldehyde from 27.6 +/- 2.5 to 48.4 +/- 17.5 microM/g tissue; and 4-hydroxyalkenal from 34.0 +/- 3.0 to 59.7 +/- 18.8 microM/g tissue, both p < 0.05) from lung explants. Treatment with the beta-adrenoreceptor agonist isoproterenol (1 ng/ml) attenuated LPS-induced release of TNF-alpha and lipid peroxidation in association with an increase in intracellular cAMP levels. The adenylate cyclase activator, forskolin, also inhibited LPS-induced changes in TNF-alpha and lipid peroxidation. In conclusion, increasing intracellular levels of cAMP through beta-adrenoreceptor activation can attenuate the acute inflammatory response induced in the lung by LPS. LPS did not significantly impair the beta-adrenoreceptor reactivity in lung explants. Lung explants allow for the quantitative assessment of pulmonary inflammatory responses independent of influences from the circulation, and thus may be a useful ex vivo model to investigate cellular and molecular mechanisms of lung injury.
 ...
PMID:Effect of adrenoreceptors on endotoxin-induced cytokines and lipid peroxidation in lung explants. 1055 44

The interaction between human neutrophils and wild-type Bordetella pertussis or mutants expressing altered lipopolysaccharide or lacking virulence factors-pertussis toxin, adenylate cyclase toxin, dermonecrotic toxin, filamentous hemagglutinin (FHA), pertactin, or BrkA-was examined. In the absence of antibodies, the wild-type strain and the mutants, with the exception of mutants lacking FHA, attached efficiently to neutrophils. The addition of opsonizing antibodies caused a significant reduction (approximately 50%) in attachment of the wild-type strain and most of the mutants expressing FHA, suggesting that bacterium-mediated attachment is more efficient than Fc-mediated attachment. Phagocytosis was also examined. In the absence of antibodies, about 12% of the wild-type bacteria were phagocytosed. Opsonization caused a statistically significant reduction in phagocytosis (to 3%), possibly a consequence of reduced attachment. Phagocytosis of most of the mutants was similar to that of the wild type, with the exception of the mutants lacking adenylate cyclase toxin. About 70% of the adenylate cyclase toxin mutants were phagocytosed, but only in the presence of opsonizing antibody, suggesting that Fc receptor-mediated signaling may be needed for phagocytosis. These studies indicate that FHA mediates attachment of B. pertussis to neutrophils, but adenylate cyclase toxin blocks phagocytosis.
 ...
PMID:Bordetella pertussis virulence factors affect phagocytosis by human neutrophils. 1067

Whooping cough is presently one of the ten most common causes of death from infectious disease worldwide. Despite a high vaccine uptake, resurgences of this disease have been observed in several countries. Virulence factors of Bordetella pertussis include agglutinogens, fimbriae, P.69/pertactin, pertussis toxin, filamentous haemagglutinin, adenylate cyclase, tracheal cytotoxin, dermonecrotic toxin, lipopolysaccharide, tracheal colonisation factor, serum resistance factor, and type III secretion. Virulence factor expression is regulated by the bvgAS locus, a two-component signal transduction system. The pathophysiologic sequence consists of attachment (fimbriae, P.69/pertactin, tracheal colonisation factor, pertussis toxin, filamentous haemagglutinin), evasion of host defence (adenylate cyclase, pertussis toxin, serum resistance factor), local effects (tracheal cytotoxin), and systemic effects (pertussis toxin). Bordetella pertussis is transmitted by respiratory droplets and causes disease only in humans. Various diagnostic methods are available, including culture, serological methods, and the polymerase chain reaction. Serotyping of isolates to detect agglutinogens 2 and 3 is useful because serotype 1,2 may be associated with higher mortality, and antibodies to these antigens (agglutinins) may be protective in both animals and humans. Immunisation using whole-cell vaccine is effective but is reactogenic. Acellular vaccines containing one to five components are being used increasingly in various countries. Protective immunity to pertussis correlates with high levels of antibody to each of pertactin, fimbriae, and pertussis toxin; however, doubt remains as to the relationship between agglutinogen 3 and fimbria 3, making results of trials investigating these virulence factors difficult to interpret.
 ...
PMID:Bordetella pertussis infection: pathogenesis, diagnosis, management, and the role of protective immunity. 1074 92

Binding experiments followed by measurement of nitric oxide release revealed an opiate alkaloid high affinity receptor with no affinity to opioids, representing a new mu-subtype receptor in the brain of the leech Theromyzon tessulatum. In addition, evidence of morphine-like substances was found in immunocytochemical studies and HPLC coupled to electrochemical detection (500 mV and 0.02 Hz). Based on previous evidence of the involvement of morphine as an immune response inhibitor, we demonstrate that in leech ganglia injection of lipopolysaccharide (LPS; a potent immunostimulatory agent derived from bacteria) provoked an increase in the level of ganglionic morphine-like substances after a prolonged latency period of 24 h (from 2.4 +/- 1.1 pmol per ganglion to 78 +/- 12.3 pmol per ganglion; P < 0.005; LPS injected 1 microg x mL-1); this effect is both concentration- and time-dependent. Finally, we have demonstrated that morphine, after binding to its own receptor, inhibits leech immunocyte activation through adenylate cyclase inhibition and nitric oxide release. This report confirms that morphine is an evolutionarily stable potent immunomodulator.
 ...
PMID:Morphine-like substance in leech ganglia. Evidence and immune modulation. 1075 61

This study examined the immunomodulatory effects of hydrogen peroxide (H(2)O(2)) in B6C3F1 mouse splenic lymphocytes. H(2)O(2) produced a marked and dose-related inhibition of both lipopolysaccharide (LPS)-induced B-cell proliferation and concanavalin A (Con A)-induced T-cell proliferation. Unexpectedly, little effect was observed with H(2)O(2) on the antibody-forming cell (AFC) response to the polyclonal B-cell activator, LPS. It was also observed that H(2)O(2) did not have any detectable effect on forskolin-stimulated adenylate cyclase, indicating that cyclic AMP (cAMP) is not a mediator of H(2)O(2)-induced suppression of the immune response. Rather, LPS-induced activation of protein kinase C (PKC) was completely inhibited when cells were pretreated with H(2)O(2) for 18 h, although PKC activity was increased approximately twofold following treatment with H(2)O(2) for 10 min. In addition, H(2)O(2) pretreatment blocked the phosphorylation of two stress-activated mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK) and p38 by LPS in a concentration-dependent fashion. Therefore, these data suggest that H(2)O(2) suppresses immune response through the desensitization of PKC, which subsequently results in inhibition of JNK and p38.
 ...
PMID:Hydrogen peroxide inhibits the immune response to lipopolysaccharide by attenuating signaling through c-Jun N-terminal kinase and p38 associated with protein kinase C. 1093 14

Previously we showed that calcitonin gene-related peptide (CGRP), a neuropeptide, inhibited lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) production and increased interleukin (IL)-6 release at low concentrations via activation of the cAMP pathway in mouse peritoneal macrophages (Mphi). In this study we examined whether CGRP could modulate IL-12 release from mouse peritoneal Mphi, and if so, what signal transduction pathway was involved. Mphi were obtained from the peritoneal exudate of male BALB/c mice. The cells were plated on culture dishes at a density of 5 x 105 cells per well and allowed to adhere for 2 hr. After incubation for 24 hr, the Mphi were cultured with 0.1 microg/ml of LPS, alone or together with CGRP (1-1000 nM) for 24 hr. The amount of IL-12 in the cell medium was measured by enzyme-linked immunosorbent assay (ELISA). The results showed that CGRP attenuated LPS-induced IL-12 release in a concentration-dependent manner. Production of IL-12 was decreased from 95.9+/-4.6 to 73.4+/-5.7 pg/ml by 100 nM CGRP. The two cAMP phosphodiesterase (PDE) inhibitors, 3-isobutyl-1-methyl-xanthine (IBMX) and rolipram, significantly potentiated the CGRP response, and the level of IL-12 was further decreased by 28% and 47%, respectively. However, CGRP had no effect on IL-12 production from unstimulated Mphi. The LPS-induced IL-12 release from Mphi could also be reduced by forskolin, an activator of adenylate cyclase, and 8-Br-cAMP, an analogue of cAMP. Using the reverse transcription-polymerase chain reaction (RT-PCR), we found that CGRP also decreased the LPS-induced IL-12 p40 mRNA levels. Furthermore, pretreatment with H89 (0.1 microM or 1 microM), an inhibitor of cAMP-dependent protein kinase, diminished CGRP effects, IL-12 production and gene expression. These data suggest that LPS-induced IL-12 release and gene expression were attenuated by CGRP via an activated cAMP-protein kinase A (PKA) pathway in mouse peritoneal Mphi.
 ...
PMID:Calcitonin gene-related peptide inhibits lipopolysaccharide-induced interleukin-12 release from mouse peritoneal macrophages, mediated by the cAMP pathway. 1101 54

We investigated, by a combined in vivo and in vitro approach, the temporal changes of islet nitric oxide synthase (NOS)-derived nitric oxide (NO) and heme oxygenase (HO)-derived carbon monoxide (CO) production in relation to insulin and glucagon secretion during acute endotoxemia induced by lipopolysaccharide (LPS) in mice. Basal plasma glucagon, islet cAMP and cGMP content after in vitro incubation, the insulin response to glucose in vivo and in vitro, and the insulin and glucagon responses to the adenylate cyclase activator forskolin were greatly increased after LPS. Immunoblots demonstrated expression of inducible NOS (iNOS), inducible HO (HO-1), and an increased expression of constitutive HO (HO-2) in islet tissue. Immunocytochemistry revealed a marked expression of iNOS in many beta-cells, but only in single alpha-cells after LPS. Moreover, biochemical analysis showed a time dependent and markedly increased production of NO and CO in these islets. Addition of a NOS inhibitor to such islets evoked a marked potentiation of glucose-stimulated insulin release. Finally, after incubation in vitro, a marked suppression of NO production by both exogenous CO and glucagon was observed in control islets. This effect occurred independently of a concomitant inhibition of guanylyl cyclase. We suggest that the impairing effect of increased production of islet NO on insulin secretion during acute endotoxemia is antagonized by increased activities of the islet cAMP and HO-CO systems, constituting important compensatory mechanisms against the noxious and diabetogenic actions of NO in endocrine pancreas.
 ...
PMID:Evaluation of islet heme oxygenase-CO and nitric oxide synthase-NO pathways during acute endotoxemia. 1128 38

Anti-inflammatory effects of cyclic AMP elevating agents were examined in a mouse model of lipopolysaccharide (LPS)-induced microvascular permeability change. Vascular permeability on the back skin was measured by the local accumulation of Pontamine sky blue (PSB) after subcutaneous injection of LPS (400 microg site-1) from Salmonella typhimurium. Dye leakage in the skin was significantly increased 2 h after injection of LPS. This LPS-induced dye leakage was suppressed by phosphodiesterase inhibitors, including pentoxifylline (160 mg kg-1), milrinone (5 - 10 mg kg-1), rolipram (0.5 - 10 mg kg-1) and zaprinast (5 - 10 mg kg-1). The dye leakage was also inhibited by beta-adrenoceptor agonists, including isoproterenol (0.5 - 5 mg kg-1) and salbutamol (0.05 - 5 mg kg-1), an adenylate cyclase activator, forskolin (5 mg kg-1), and a cell permeable cyclic AMP analogue, 8-bromo-cyclic AMP (8-Br-cAMP, 10 mg kg-1). LPS caused a transient increase in serum TNF-alpha level peaking at 1 h after the injection. This increase in serum TNF-alpha was completely blocked by a pretreatment with pentoxifylline (160 mg kg-1), milrinone (5 mg kg-1), rolipram (1 mg kg-1), zaprinast (10 mg kg-1), salbutamol (0.5 mg kg-1), forskolin (1 mg kg-1) and 8-Br-cAMP (10 mg kg-1). LPS caused an increase in serum IL-1alpha level peaking at 3 h after injection. This increase in serum IL-1alpha was not significantly suppressed by the cyclic AMP elevating agents. Our study suggests that cyclic AMP elevating agents attenuate LPS-induced microvascular permeability change by suppressing TNF-alpha up regulation.
 ...
PMID:Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)-induced microvascular permeability change in mouse skin. 1135 Aug 59


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