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)

Solid-phase enzyme immunoassays (with high-turnover acetylcholinesterase as label) for human IL-1 alpha and IL-1 beta were applied to quantify the production of these factors by cultured human umbilical vein endothelial cells (HUVECs). Immunoreactive IL-1s exhibited a typical pattern in HUVECs, under either basal or stimulated conditions: the alpha form was predominant over the beta form and the cell-associated IL-1s measured were more abundant than the material recovered in the supernatants. Bacterial lipopolysaccharide (LPS, 0.5-5 micrograms/ml) significantly increased the basal production of IL-1. Pulses of recombinant IL-1 alpha or -beta or of TNF-alpha followed by a 24 h culture period were also associated with an increased endothelial production of IL-1, with a higher proportion of material secreted in the supernatants as compared with LPS. Other cytokines applied as pulses failed to induce the IL-1s or to modify LPS-induced production of IL-1: they include IL-2, immune interferon, GM-CSF, TGF-beta and EGF. Pharmacological modulators of LPS-induced IL-1 production were identified: glucocorticoids were inhibitors whereas retinoic acid and 1.25-dihydroxy-vitamin D3 had no effects and prostaglandin E2 and IBMX were weak inhibitors. There is no evidence that IL-1 alpha and IL-1 beta are regulated differently in HUVECs, but several significant differences from the monocyte were observed in the regulation of HUVEC IL-1 production.
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PMID:Pharmacological modulation of interleukin 1 production by cultured endothelial cells from human umbilical veins. 169 6

Blue-green algae toxins include (1) hepatotoxic peptides that are known to be toxic to cattle, dogs, swine, waterfowl, and sometimes other species; (2) a nicotinic agonist neurotoxin that appears to be toxic to a wide range of animal species; (3) a peripheral-acting cholinesterase inhibitor that is very toxic to swine, birds, and dogs; (4) toxins that impair nervous transmission by blocking sodium channels in nerve cells; and (5) lipopolysaccharide endotoxins. This article provides current information on the mechanisms of action of the primary toxins recognized to date as well as on procedures important in the diagnosis and management of some of the more common cyanobacterial toxicoses in livestock and waterfowl.
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PMID:Algae intoxication in livestock and waterfowl. 250 41

The time course of immunosuppression induced by acute treatment with O,O,S-trimethyl phosphorothioate (OOS-TMP), an impurity in technical formulations of malathion, was examined in female C57B1/6 mice. Both cell-mediated and humoral immune responses were examined and included allospecific cytotoxic T cells, proliferative response to mitogens, interleukin-2 production and antibody production to sheep red blood cells. OOS-TMP pretreatment led to a reversible suppression of the generation of cytotoxic T lymphocytes and antibody-secreting cells to sheep erythrocytes. However, the mitogenic response of splenocytes from animals treated with nontoxic doses of OOS-TMP (as measured by body weight loss, serum cholinesterase levels and splenic lymphocyte number) to concanavalin A was not significantly suppressed, but the response to the B cell mitogen lipopolysaccharide was slightly decreased on day 1 following treatment. In contrast, interleukin-2 production was elevated by 24 h following treatment, but had returned to control levels by day 7. These data suggest that OOS-TMP was able to block the generation of cytotoxic T lymphocytes and antibody responses at doses of OOS-TMP that did not affect body weight or splenic lymphocyte number and this suppression was reversible.
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PMID:Organophosphorus pesticide immunotoxicity: effects of O,O,S-trimethyl phosphorothioate on cellular and humoral immune response systems. 349 28

To evaluate the cause of the vulnerability to infections in the elderly, the ability of neutrophil to generate reactive oxygen species was assessed by a luminol-dependent chemiluminescence (CL) assay after stimulation with non-opsonized zymosan, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans and lumispheres in elderly patients aged 70 to 93 years. The integrated CL for 20 minutes of whole blood and neutrophils induced by zymosan in the elderly was significantly lower than that in healthy young adults, and the integrated CL of neutrophils induced by lumispheres was also significantly lower in the elderly aged 80 years and over. When bacterial infection occurred in the elderly, the levels of CL were elevated and decreased in the convalescence. This response is proper for host-defense mechanism against infection. However, whole blood CL response was not fully activated in any patients of the elderly during bacterial infection. In these cases lower white blood cell counts, lower neutrophil counts, or the decreased level of the serum total protein, albumin, total cholesterol or cholinesterase were observed. Relationship between malnutrition and the ability of neutrophil to generate reactive oxygen species was suggested. Furthermore, I evaluated the priming effect of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) on whole blood CL. The CL responses stimulated with non-opsonized zymosan or P. aeruginosa were enhanced by pretreatment with TNF-alpha and LPS in healthy young adults. On the other hand, no significant priming effect was observed when blood from elderly patients were incubated with each primer. These findings suggest that the impairment in the generation of reactive oxygen species of the neutrophils and the decrease in reactivity to LPS and TNF-alpha that activate neutrophils at the site of infection and potentiate host defense against invading bacteria, may contribute to susceptibility to infection in the elderly.
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PMID:[Study of neutrophil dysfunctions in the elderly using a chemiluminescence method]. 782 5

Oral chlorpyrifos (CHP) induces hypothermia followed by a fever that persists for several days in the rat. To understand the neuro-immune mechanisms of CHP-induced fever, we compared the tolerance and cross-tolerance between CHP and the fever elicited by lipopolysaccharide (LPS) (Escherichia coli). Female rats were administered the corn oil (CO) vehicle or CHP (10 mg/kg; p.o.) daily for 4 days while core temperature (Tc) and motor activity (MA) were monitored by telemetry. There was a reduction in Tc followed by an elevation the next day after each CHP treatment. The day after the last CHP treatment, rats were administered saline or 50 microg/kg LPS (i.p.). CHP-treated rats had a smaller LPS fever that was attributed to their elevated baseline Tc. In another study, rats were dosed with saline or LPS daily for three days. By the time of the third LPS injection there was no febrile response, indicating tolerance to LPS. Rats were then dosed with CO or CHP (10 mg/kg) 24 h after the third LPS treatment. LPS-tolerant rats displayed an accentuated hypothermic and febrile response to CHP. Plasma cholinesterase activity was unaffected by repeated LPS treatment, suggesting that the metabolism of CHP in the liver was unaffected by LPS. Overall, the neural-immune mechanisms for LPS fever is distinct from that of CHP in view of marked difference in mechanisms of tolerance.
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PMID:Delayed febrile effects of chlorpyrifos: is there cross-tolerance to bacterial lipopolysaccharide? 984 93

Oral exposure to chlorpyrifos (CHP) in the rat results in an initial hypothermic response followed by a delayed fever. Fever from infection is mediated by the release of cytokines, including interleukin-6 (IL-6) and tumor necrosis factor (TNF alpha). This study determined if the CHP-induced fever involves cytokine-mediated mechanisms similar to that of infectious fevers. Long-Evans rats were gavaged with the corn oil vehicle or CHP (10-50 mg/kg). The rats were euthanized and blood collected at various times that corresponded with the hypothermic and febrile effects of CHP. Plasma IL-6, TNF alpha, cholinesterase activity (ChE), total iron, unsaturated iron binding capacity (UIBC), and zinc were measured. ChE activity was reduced by approximately 50% 4 h after CHP. There was no effect of CHP on IL-6 when measured during the period of CHP-induced hypothermia or fever. TNF alpha levels nearly doubled in female rats 48 h after 25 mg/kg CHP. The changes in plasma cytokine levels following CHP were relatively small when compared to > 1000-fold increase in IL-6 and > 10-fold rise in TNF alpha following lipopolysaccharide (E. coli; 50 microg/kg; i.p.)-induced fever. This does not preclude a role of cytokines in CHP-induced fever. Nonetheless, the data suggest that the delayed fever from CHP is unique, involving mechanisms other than TNF alpha and IL-6 release into the circulation characteristic of infectious fevers.
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PMID:Are circulating cytokines interleukin-6 and tumor necrosis factor alpha involved in chlorpyrifos-induced fever? 1041 84

The organophosphate pesticide, malathion, was evaluated for effects on immune function in female SJL/J mice. Commercial grade malathion was dissolved in corn oil and administered at doses of 0.018-180 mg/kg to mice via oral gavage on alternate days for 28 days. Exposure to malathion did not alter brain acetylcholinesterase activity, body weight gain, organ/body weight ratios or food and water consumption during the treatment period. Malathion enhanced the primary IgM antibody response to sheep red blood cells (SRBCs) by approximately 150% (P<0.02) at all doses tested when the response was expressed per 10(6) viable spleen cells and per spleen. B-lymphocyte blastogenesis induced by lipopolysaccharide (LPS, P=0.10) was not affected by malathion exposure. T-lymphocyte blastogenesis induced by concanavalin A (ConA, P=0.23) and phytohemagglutinin (PHA-P, P=0.24) also was unaffected by treatment with malathion. Malathion had no effect on splenic macrophage phagocytosis (P>0.11). These results indicate that repeated oral administration of commercial-grade malathion increased antibody production following immunization with a T-lymphocyte dependent antigen at doses as low as 0.018 mg/kg, which is below the human allowable daily intake (0.02 mg/kg). These changes occurred in the absence of B- or T-lymphocyte hyper responsiveness or alterations in macrophage phagocytosis. Immune system alterations at a sub-clinical level following exposure to a commercial formulation of malathion may have an important impact on human and animal health risk assessment. Therefore, further investigation into the mechanisms responsible for the increased antibody production is warranted.
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PMID:Increased T-lymphocyte dependent antibody production in female SJL/J mice following exposure to commercial grade malathion. 1175 89

Alzheimer's disease is associated with glial activation and increased levels of the cytokines as well as impaired forebrain cholinergic function. Current therapies focus on enhancing cholinergic function by administrating acetylcholinesterase inhibitors, such as galantamine. Epidemiological results also suggest that anti-inflammatory therapies might be effective in slowing the onset of the symptoms of Alzheimer's disease. The current study investigated the ability of a nitric oxide (NO)-donating derivative of the nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen, HCT1026, to reduce brain inflammation in young rats. Inflammation was produced by chronic infusion of lipopolysaccharide (LPS) into the 4th ventricle. The release of NO from HCT1026 requires the action of esterase enzymes. The current study determined whether the effectiveness of HCT1026 was attenuated by simultaneous treatment with the acetylcholinesterase inhibitor galantamine. Daily administration of the HCT1026 significantly reduced microglial activation and these effects were not attenuated by galantamine therapy.
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PMID:A nitric oxide-donating flurbiprofen derivative reduces neuroinflammation without interacting with galantamine in the rat. 1239 20

Immune regulation, either via the autonomic nervous system or by a proposed "non-neuronal" cholinergic system, suggests that the immune system may be susceptible to perturbation by compounds affecting cholinergic function. Here, the current UK and US nerve agent pre-treatment, pyridostigmine bromide (PB) and the related anti-acetylcholinesterase (AChE) compounds physostigmine (PHY) and BW284c51 were tested for their ability to affect mouse splenocyte function in vitro. In addition, PB, at a dose equivalent to that received during pre-treatment for nerve agent poisoning, was tested for its effect on a T-cell-dependent humoral response to antigen in vivo in the mouse. None of the anti-AChEs tested affected concanavalin A (Con A)-, anti-CD3- or lipopolysaccharide LPS-driven splenocyte proliferation, in vitro, at concentrations expected to give effective nerve agent pre-treatment. However, higher concentrations (>100 microM) particularly of PHY caused some inhibition of the proliferative responses. In vivo, PB or saline was administered via 28-day mini-osmotic pumps to give a 25-40% inhibition of whole blood AChE in the PB-treated animals. During PB or saline administration, primary and secondary doses (i.p.) of sheep red blood cells (SRBC) were given and the humoral response determined by monitoring anti-SRBC IgM and IgG levels. Splenocytes isolated from the experimental animals were also examined for their proliferative and cytokine responses to stimulation. No remarkable effects of PB were seen during the period of AChE inhibition on the humoral immune response. However, a modest elevation in IL-2 and IFN(gamma) in Con A-stimulated lymphocytes was seen in PB-treated animals following pump removal. Overall these data suggest that, in vivo, the SRBC stimulated T-cell-dependent immune response is unaffected by the administration of PB at pre-treatment doses.
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PMID:A T-cell-dependent humoral immune response is preserved during the administration of the nerve agent pre-treatment pyridostigmine bromide in a murine model. 1568 49

To study the role of the stress-induced "readthrough" acetylcholinesterase splice variant, AChE-R, in thrombopoiesis, we used transgenic mice overexpressing human AChE-R (TgR). Increased AChE hydrolytic activity in the peripheral blood of TgR mice was associated with increased thrombopoietin levels and platelet counts. Bone marrow (BM) progenitor cells from TgR mice presented an elevated capacity to produce mixed (GEMM) and megakaryocyte (Mk) colonies, which showed intensified labeling of AChE-R and its interacting proteins RACK1 and PKC. When injected with bacterial lipopolysaccharide (LPS), parent strain FVB/N mice, but not TgR mice, showed reduced platelet counts. Therefore, we primed human CD34+ cells with the synthetic ARP26 peptide, derived from the cleavable C-terminus of AChE-R prior to transplantation, into sublethally irradiated NOD/SCID mice. Engraftment of human cells (both CD45+ and CD41+ Mk) was significantly increased in mice that received ARP26-primed CD34+ human cells versus mice that received fresh nonprimed CD34+ human cells. Moreover, ARP26 induced polyploidization and proplatelet shedding in human MEG-01 promegakaryotic cells, and human platelet engraftment increased following ex vivo expansion of ARP26-treated CD34+ cells as compared to cells expanded with thrombopoietin and stem cell factor. Our findings implicate AChE-R in thrombopoietic recovery, suggesting new therapeutic modalities for supporting platelet production.
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PMID:Stress-induced cholinergic signaling promotes inflammation-associated thrombopoiesis. 1638 Apr 50


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