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)

The effects of Astragali radix extract on interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha productions, prostaglandin E2 (PGE2) biosynthesis, and leukotriene C4 (LTC4) production from lipopolysaccharide (LPS)-stimulated human amnion cells were investigated. Amnion cells produced detectable amounts of both IL-6 and TNF-alpha under LPS-stimulated conditions. Astragalus extract inhibited the production of IL-6. However, TNF-alpha production was not inhibited by the extract on L929 cytotoxicity assay. Treatment of amnion cells with LPS for up to 24 h resulted in an increase in PGE2 release in a concentration- and time-dependent manner. The extract (150 mg/ml) significantly inhibited the output of PGE2 by amnion cells (p<0.01). The arachidonate lipoxygenase metabolite (LTC4) was increased by LPS treatment of amnion cells. Astragalus extract (30 mg/ml) inhibited LTC4 production by approximately 65% throughout the culture period. These results suggest that Astragali radix extract may have a role in inhibiting bacterial infection-associated preterm labor by suppressing the productions of IL-6, PGE2, and LTC4 by human amnion cells.
 ...
PMID:Effect of Astragali radix extract on lipopolysaccharide-induced inflammation in human amnion. 1182 62

There is evidence of molecular cross talk between inflammatory mediators such as nitric oxide (NO) and prostaglandins (PG), which may regulate tissue homeostasis and contribute to pathophysiological processes. Here we examine the role of endogenous arachidonic acid (AA) and its AA metabolites in the regulation of NO release by lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7. Our results suggest that bromoenol lactone-sensitive phospholipase A(2) is involved in AA release and the subsequent PG and leukotriene (LT) production. The cyclooxygenase inhibitor, indomethacin, and lipoxygenase inhibitors such as baicalein and zileuton blocked the dose-dependent PGE(2) or LTB(4) and nitrite (NO(2)(-)) production induced by LPS. Furthermore, the effects of indomethacin were reverted by exogenous PGE(2) and forskolin, whereas AH23848B, an EP(4) PGE(2) subtype receptor antagonist, decreased NO(2)(-) release. On the other hand, the effect of baicalein on NO(-)(2) production was reverted by exogenous LTB(4) and the fibrate WY 14,643, a natural and a synthetic peroxisome proliferator-activated receptor alpha (PPAR alpha), respectively. Thus, PGE(2) via EP(4) receptor/cAMP and LTB(4) via PPAR alpha may be involved in the control of NO synthesis by LPS in macrophage RAW 264.7 cultures.
 ...
PMID:Role of Ca(2+)-independent phospholipase A(2) and cyclooxygenase/lipoxygenase pathways in the nitric oxide production by murine macrophages stimulated by lipopolysaccharides. 1200 43

Glutathione is an important cellular antioxidant present at high concentrations in the brain. We have previously demonstrated that depletion of glutathione in mesencephalic cultures results in cell death and that the presence of glia is necessary for the expression of toxicity. Cell death following glutathione depletion can be prevented by inhibition of lipoxygenase activity, implicating arachidonic acid metabolism in the toxic events. In this study we examined the effect of glial activation, known to cause secretion of cytokines and release of arachidonic acid, on the toxicity induced by glutathione depletion. Our data show that treatment with the endotoxin lipopolysaccharide activated glial cells in mesencephalic cultures, increased interleukin-1beta in microglia and caused depletion of glutathione. The overall effect of lipopolysaccharide treatment, however, was protection from damage caused by glutathione depletion. Addition of cytokines or growth factors, normally secreted by activated glia, did not modify L-buthionine sulfoximine toxicity, although basic fibroblast growth factor provided some protection. A large increase in the protein content and the activity of Mn-superoxide dismutase, observed after lipopolysaccharide treatment, may indicate a role for this mitochondrial antioxidant enzyme in the protective effect of lipopolysaccharide. This was supported by the suppression of toxicity by exogenous superoxide dismutase. Our data suggest that superoxide contributes to the damage caused by glutathione depletion and that up-regulation of superoxide dismutase may offer protection in neurodegenerative diseases associated with glutathione depletion and oxidative stress.
 ...
PMID:Lipopolysaccharide prevents cell death caused by glutathione depletion: possible mechanisms of protection. 1220 5

Arachidonic acid (AA) mainly released from the cell membrane by phospholipase A(2) (PLA(2)) is converted to eicosanoids by the action of cyclooxygenase (COX) and lipoxygenase (LO). In order to find the specific inhibitors of AA metabolism especially PLA(2) and COX-2, 300 plant extracts were evaluated for their inhibitory activity on PGD(2) production from cytokine-induced mouse bone marrow-derived mast cells in vitro. From this screening procedure, the methanol extract of Salvia miltiorrhiza was found to inhibit PGD(2) production and the ethyl acetate subfraction gave the strongest inhibition of five subfractions tested. From this ethyl acetate subfraction, an activity-guided isolation finally gave tanshinone I as an active principle. This investigation deals with the effects of tanshinone I on AA metabolism from lipopolysaccharide (LPS)-induced RAW 264.7 cells and in vivo antiinflammatory activity. Tanshinone I inhibited PGE(2) formation from LPS-induced RAW macrophages (IC(50) = 38 microM). However, this compound did not affect COX-2 activity or COX-2 expression. Tanshinone I was found to be an inhibitor of type IIA human recombinant sPLA(2)(IC(50) = 11 microM) and rabbit recombinant cPLA(2) (IC(50) = 82 microM). In addition, tanshinone I showed in vivo antiinflammatory activity in rat carrageenan-induced paw oedema and adjuvant-induced arthritis.
 ...
PMID:Effects of tanshinone I isolated from Salvia miltiorrhiza bunge on arachidonic acid metabolism and in vivo inflammatory responses. 1241 May 40

1. Cyclo-oxygenase (COX) and lipoxygenase (LO) share a common substrate, arachidonic acid. Aspirin and related drugs inhibit COX activity. In a subset of patients with asthma aspirin induces clinical symptoms associated with increased levels of certain LO products, a phenomenon known as aspirin-sensitive asthma. The pharmacological pathways regulating such responses are not known. 2. Here COX-1 and LO activity were measured respectively by the formation of thromboxane B(2) (TXB(2)) or leukotrienes (LT) C(4), D(4) and E(4) in whole blood stimulated with A23187. COX-2 activity was measured by the formation of prostaglandin E(2) (PGE(2)) in blood stimulated with lipopolysaccharide (LPS) for 18 h. 3. No differences in the levels of COX-1, COX-2 or LO products or the potency of drugs were found in blood from aspirin sensitive vs aspirin tolerant patients. Aspirin, indomethacin and nimesulide inhibited COX-1 activity, without altering LO activity. Indomethacin, nimesulide and the COX-2 selective inhibitor DFP [5,5-dimethyl-3-(2-isopropoxy)-4-(4-methanesulfonylphenyl)-2(5H)-furanone] inhibited COX-2 activity. NO-aspirin, like aspirin inhibited COX-1 activity in blood from both groups. However, NO-aspirin also reduced LO activity in the blood from both patient groups. Sodium salicylate was an ineffective inhibitor of COX-1, COX-2 or LO activity in blood from both aspirin-sensitive and tolerant patients. 4. Thus, when COX activity in the blood of aspirin-sensitive asthmatics is blocked there is no associated increase in LO products. Moreover, NO-aspirin, unlike other NSAIDs tested, inhibited LO activity in the blood from both aspirin sensitive and aspirin tolerant individuals. This suggests that NO-aspirin may be better tolerated than aspirin by aspirin-sensitive asthmatics.
 ...
PMID:Effects of non-steroidal anti-inflammatory drugs on cyclo-oxygenase and lipoxygenase activity in whole blood from aspirin-sensitive asthmatics vs healthy donors. 1242 75

The influence of several eicosanoids of the lipoxygenase pathway was examined in an ex vivo system of human whole blood subjected to stimulation by lipopolysaccharide (LPS). Exogenously added leukotriene B4 [5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4)] or 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) significantly (P<0.05) enhanced LPS-evoked expression of monocyte tissue factor (TF) activity in a concentration-dependent manner. 15(S)-HETE, on the other hand, exerted such activity only when added at certain concentrations, whereas 5(S)-HETE was devoid of any apparent activity. LPS-induced TF activity was inhibited by the lipoxygenase inhibitors nordihydroguaiaretic acid, CGS 23885 and ZM 230487, by 59, 32 and 88%, respectively. Furthermore, the production of LTB4 in LPS-stimulated whole blood was investigated, in the absence or presence of either tumor necrosis factor alpha (TNFalpha) or phorbol-12-myristate-13-acetate (PMA). LPS alone induced a moderate time-dependent and concentration-dependent release of LTB4, reaching the maximum concentration (1260 +/- 202 pg/ml) within 90 min at 5 ng/ml LPS. The prior and concurrent presence of PMA (5 ng/ml) or TNFalpha (10 ng/ml) further enhanced the LTB4 production approximately twofold (P < 0.05). TNFalpha added alone evoked approximately twice the LTB4 production seen when LPS (2200 +/- 243 versus 1260 +/- 203 pg/ml) was added alone. Considering these results, LPS and TNFalpha emerge as important agonists of LTB4 production in whole blood. LTB4 in turn appears to be of importance for the expression of TF in monocytes, potentially amplifying the thrombogenic potential of these cells.
 ...
PMID:Ex-vivo regulation of endotoxin-induced tissue factor in whole blood by eicosanoids. 1254 27

Recognition of pathogens by immune cells initiates the release of numerous signaling molecules, including cytokines and eicosanoids. Here, we describe a simple procedure by which eicosanoids such as prostaglandin E(2) (PGE(2)), leukotriene B(4) (LTB(4)) and thromboxane B(2) (TxB(2)) can be measured using commercial enzyme immunoassays (EIAs) in the supernatant of whole blood stimulated with inflammatory stimuli. This is illustrated for numerous stimuli. The kinetics by which lipopolysaccharide (LPS) induces cyclooxygenase (COX)-2 expression in this setup were determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). The eicosanoid response of the blood of 160 healthy volunteers to 1 microg/ml LPS was measured. To determine whether the action of a drug in vivo is represented ex vivo in the eicosanoid response of blood, one volunteer took a standard dose of a number of commercially available cyclooxygenase inhibitors on different days and the eicosanoid response of his blood to LPS was determined before ingestion as well as 2 and 6 h afterwards. The efficacy of the different pharmaceuticals on cyclooxygenase but not lipoxygenase products or cytokines could be monitored ex vivo. Similarly, ex vivo eicosanoid release was measured in blood from 10 volunteers who had taken 50 mg flurbiprofen. The method described extends approaches for studying whole blood cytokine release to the lipid mediators formed from arachidonic acid. These important signaling molecules represent targets for pharmacological intervention, which can now be monitored in vitro, as well as ex vivo employing the same model. Furthermore, the assay could be used to characterize the immune status of patient groups or to monitor the course of disease.
 ...
PMID:Determination of the eicosanoid response to inflammatory stimuli in whole blood and its pharmacological modulation ex vivo. 1279 39

High-fructose feeding causes diet-induced alterations of lipid metabolism and decreased insulin sensitivity with alterations of hepatic pyruvate dehydrogenase and hepatic very low-density lipoprotein secretion. Inflammatory cytokines also induce dramatic changes in lipid metabolism, particularly in serum triglycerides via increased hepatic secretion and/or delayed clearance of very low-density lipoprotein. The aim of this study was to determine whether the mechanism of lipid dysregulation in the high-fructose diet is induced by stress response pathways. Animals were fed a high-fructose diet for 14 d to establish hypertriglyceridemia and then were treated with lipoxygenase inhibitors for 4 d concurrent with the diet. At the end of drug treatment, the animals were divided into two groups and treated with lipopolysaccharide or a vehicle. Serum samples were taken pretreatment and posttreatment, and liver tissue was harvested at the end of study. Serum samples were tested for metabolic parameters, and the tissue samples were tested for metabolic and stress pathway responses. Our results show that fructose-fed rats have changes in the c-Jun N-terminal kinase pathway with correspondingly elevated activator protein-1 activity, consistent with an inflammatory response. Treatment with lipoxygenase inhibitors reversed the hypertriglyceridemia and also reduced activator protein-1 activation, suggesting that the basis for lipid dysregulation in this model is due to activation of inflammatory pathways in the liver.
 ...
PMID:High dietary fructose induces a hepatic stress response resulting in cholesterol and lipid dysregulation. 1457 75

Insect cellular immune reactions to bacterial infection include nodule formation. Eicosanoids mediate several cellular actions in the nodulation process, including formation of hemocyte microaggregates, an early step. In previous work, we reported that isolated hemocytes produce and secrete eicosanoids that influence hemocyte behavior in response to bacterial challenge. We also reported that microaggregate formation in response to challenge was mediated by prostaglandins (PGs), but not by products of the lipoxygenase (LOX) pathways. In this paper we describe experiments designed to test the idea that exposing isolated hemocytes to lipopolysaccharide (LPS) evokes formation of hemocyte microaggregates and this cellular action is mediated by PGs. Results show that isolated hemocyte preparations challenged with LPS formed more hemocyte microaggregates than unchallenged preparations (6.9x10(3) microaggregates/ml hemolymph vs. 2.5x10(3) microaggregates/ml hemolymph). LPS challenge stimulated formation of hemocyte microaggregates in a dose dependent manner. Experimental groups pretreated with cyclooxygenase inhibitors produced fewer hemocyte microaggregates in response to LPS challenge than untreated control groups. The formation of hemocyte microaggregates was not influenced by LOX inhibitors. Furthermore, the influence of dexamethasone was reversed by supplementing the experimental groups with the eicosanoid precursor fatty acid molecule, arachidonic acid and PGH(2). Palmitic acid, which is not substrate for eicosanoid biosynthesis, did not reverse the effects of dexamethasone on the formation of microaggregates. The LOX product 5(S)hydroperoxyeicosa-6E,8Z,11Z,14Z-tetraenoic acid also did not reverse the effects of dexamethasone. These results are consistent with similar investigations performed with bacterial suspensions. We infer that isolated hemocyte preparations recognize and react to LPS by forming microaggregates and this reaction is mediated by PGs, but not products of the LOX pathway.
 ...
PMID:Lipopolysaccharide evokes microaggregation reactions in hemocytes isolated from tobacco hornworms, Manduca sexta. 1512 2

The present study underlines the importance of phospholipase A2 (PLA2)- and lipoxygenase (LO)-mediated signaling processes in the regulation of inducible nitric oxide synthase (iNOS) gene expression. In glial cells, lipopolysaccharide (LPS) induced the activities of PLA2 (calcium-independent PLA2; iPLA2 and cytosolic PLA2; cPLA2) as well as gene expression of iNOS. The inhibition of cPLA2 by methyl arachidonyl fluorophosphates (MAFP) or antisense oligomer against cPLA2 and inhibition of iPLA2 by bromoenol lactone reduced the LPS-induced iNOS gene expression and NFkappaB activation. In addition, the inhibition of LO by nordihydroguaiaretic acid (NDGA; general LO inhibitor) or MK886 (5-LO inhibitor), but not baicalein (12-LO inhibitor), completely abrogated the LPS-induced iNOS expression. Because NDGA could abrogate the LPS-induced activation of NFkappaB, while MK886 had no effect on it, LO-mediated inhibition of iNOS gene induction by LPS may involve an NFkappaB-dependent or -independent (by 5-LO) pathway. In contrast to LO, however, the cyclooxygenase (COX) may not be involved in the regulation of LPS-mediated induction of iNOS gene because COX inhibition by indomethacin (general COX inhibitor), SC560 (COX-1 inhibitor), and NS398 (COX-2 inhibitor) affected neither the LPS-induced iNOS expression nor activation of NFkappaB. These results indicate a role for cPLA2 and iPLA2 in LPS-mediated iNOS gene induction in glial cells and the involvement of LO in these reactions.
 ...
PMID:Involvement of phospholipase A2 and lipoxygenase in lipopolysaccharide-induced inducible nitric oxide synthase expression in glial cells. 1577 87


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