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)

We have studied activation of phospholipase (PL) C and PLD in liver macrophages labelled with [3H]arachidonic acid. Zymosan, phorbol 12-myristate 13-acetate (PMA), A23187 and fluoride but not arachidonic acid or lipopolysaccharide (LPS) induce an activation of PLD ([3H]phosphatidylethanol (PEt) accumulation). An activation of PLC ([3H]diacylglycerol (DAG) accumulation) is measured with zymosan, PMA and fluoride but not with A23187, LPS or arachidonic acid whereas inositol phosphates are formed with zymosan, only. Removal of extracellular calcium reduces the formation of [3H]PEt and [3H]DAG while pretreatment of the cells with dexamethasone reduces [3H]PEt formation, only. PMA- and zymosan-induced activation of PLD and PMA-induced activation of PLC both seem to be mediated by protein kinase (PK) C-beta whereas zymosan-induced activation of PLC is negatively controlled by PKC-delta. We could furthermore present evidence that the release of [3H]arachidonic acid in these cells occurs independent of an activation of PLD.
 ...
PMID:Differential regulation of phospholipase D and phospholipase C by protein kinase C-beta and -delta in liver macrophages. 851 98

This study compared the effects of intracellular pathway inhibitors on tumor necrosis factor-alpha (TNF-alpha) release from human monocytes. Cells were stimulated with peptidoglycan (PG) from Staphylococcus epidermidis or with Escherichia coli lipopolysaccharide (LPS), both in the presence of 10% human serum. Of 10 substances tested, only the protein tyrosine kinase inhibitor tyrphostin AG 126 discriminated significantly between PG and LPS: TNF-alpha release induced by PG, but not by LPS, was dose-dependently suppressed. The results obtained with other modulatory substances, including different protein kinase and G protein inhibitors, suggest that calmodulin-dependent protein kinase, protein tyrosine kinase, and a cholera-toxin-sensitive G protein are involved in both PG- and LPS-induced TNF-alpha release. Further, drugs such as pentoxifylline, chloroquine, and the antioxidant apocynin similarly inhibited TNF-alpha release by PG- as well as LPS-stimulated cells.
 ...
PMID:Intracellular pathways involved in tumor necrosis factor-alpha release by human monocytes on stimulation with lipopolysaccharide or staphylococcal peptidoglycan are partly similar. 853 61

We recently reported that cyclic AMP (cAMP) specifically inhibits lipopolysaccharide (LPS)-induced interleukin 1 beta (IL-1 beta) transcription initiation in astrocytic cells but enhances the LPS induction of IL-1 beta in monocytic cells. The purpose of this study was to determine how cAMP differentially regulates LPS-induced IL-1 beta transcription in these two cell types. Two essential components of the mitogen-activated protein (MAP) kinase signal-transduction pathway, extracellular-signal-regulated kinase (ERK2; p41 mapk) and Raf-1, have been shown to be targets of LPS stimulation in other cell types, and therefore may be linked to the regulation of IL-1 beta transcription. In the human astrocytic cell line, U-373MG, LPS was found to strongly activate (and cAMP to inhibit) both ERK2 and Raf-1. In the human monocytic cell line, THP-1, LPS minimally activated ERK2 and did not activate Raf-1. These findings suggest that, in astrocytic cells, elevated intracellular cAMP levels may negatively regulate LPS activation of IL-1 beta via the MAP kinase signalling pathway. In contrast, this pathway is not significantly activated by LPS in monocytic cells, thus inhibition by elevated intracellular cAMP levels would not affect IL-1 beta transcription.
 ...
PMID:Differential induction of the mitogen-activated protein kinase pathway by bacterial lipopolysaccharide in cultured monocytes and astrocytes. 857 86

The roles of calcium and/or of the other cellular transduction pathways, and of nitric oxide (NO) on the induction of metallothionein (MT) mRNA by lipopolysaccharide (LPS) has been studied in rat primary cell culture, using inhibitors of protein kinase pathways (H-7, W-7 and TMB-8) and NO production inhibitors (L-NAME, PTIO). LPS exposure led to a rapid increase of MT-mRNA and a peak level revealed 2.5-fold induction as compared to control for 6h incubation at a dose of 3.0 mg/L. A dose of 5.0 and 10.0 mg/L of LPS also provided the same level of MT-mRNA induction. The inhibition of MT induction by LPS was observed with L-NAME, PTIO, but not H-7, W-7. These findings indicate that the alteration of cellular calcium concentration and distribution does not relate to the induction of MT-mRNA by LPS in hepatocytes and that protein kinase C and calmodulin dependent protein kinase pathways have not contributed to MT-mRNA induction by LPS. Finally, the present results show that NO plays an important role in MT induction by LPS.
 ...
PMID:Nitric oxide mediated metallothionein induction by lipopolysaccharide. 858 48

A new member of the mitogen-activated protein kinase family, alternatively termed CSBP, p38, or RK, has been identified independently by several laboratories recently. Activation of this novel protein kinase via dual phosphorylation has been observed in different cell systems upon stimulation by a wide spectrum of stimuli, such as physicochemical stress and treatment with lipopolysaccharide or proinflammatory cytokines such as interleukin-1 and tumor necrosis factor. Furthermore, CSAID cytokine biosynthesis inhibitors have now been determined to be potent and selective inhibitors of CSBP/p38/RK kinase activity. These inhibitors will help to dissect signaling pathways involved in inflammatory responses. In particular, for the first time a definitive signal transduction pathway can be prescribed to the action of lipopolysaccharide in cytokine production in macrophages.
 ...
PMID:Role of CSB/p38/RK stress response kinase in LPS and cytokine signaling mechanisms. 860 87

Treatment of human monocytes with vascular endothelial growth factor (VEGF) isolated from tumor cell supernatants was reported to induce monocyte activation and migration. In this study we show that recombinant human VEGF165, and VEGF121 had a maximal effect on human monocyte migration at 65 to 250 pmol/L. Chemotactic activity of VEGF165 was inhibited by a specific antiserum against VEGF, by heat treatment of VEGF165, and by protein kinase inhibitors. In addition, we could show that VEGF-stimulated monocyte migration is mediated by a pertussis toxin-sensitive GTP-binding protein. Placenta growth factor (PlGF152), a heparin-binding growth factor related to VEGF, was also chemotactic for monocytes at concentrations between 2.5 and 25 pmol/L. In accordance with these findings, human monocytes showed specific and saturable binding for 125I-VEGF165 (half-maximal binding at 1 to 1.5 nmol/L). Using Northern blot analysis, we further could show that human monocytes express only the gene for the VEGF receptor type, flt-1, but not for the second known VEGF receptor, KDR. Resting monocytes expressed low levels of flt-1 gene only. Brief exposure (2 to 4 hours) of human monocytes to lipopolysaccharide, a prototypic monocyte activator, led to a significant upregulation of the flt-1 mRNA level. The results presented here suggest that monocyte chemotaxis in response to VEGF and most likely to PlGF152 is mediated by flt-1 and thus show a possible function for the VEGF-receptor flt-1.
 ...
PMID:Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. 860 50

Persistent human immunodeficiency virus (HIV) infection of human monocytes and macrophages increases I kappa B alpha degradation, resulting in the activation of NF-kappa B, a key transcription factor in the regulation of the HIV long terminal repeat. The signal transduction pathways leading to NF-kappa B activation in cells of the monocytic lineage, especially those regulated by HIV infection, and their relevance in regulating viral persistence remain unknown. Both p21ras and its downstream Raf-1 kinase participate in the transduction of signals initiated from a variety of cell surface receptors and in the regulation of transcription factors. We have studied whether the Ras-Raf pathway is functional and participates in HIV-mediated NF-kappa B activation in monocytic cells. Constitutively active p21ras (v-H-Ras) activated NF- kappa B-dependent transcription and induces the nuclear translocation of a bona fide p65/p50 heterodimer by targeting I kappa B alpha. In addition, the constitutively active form of Raf (RafBXB) also increases the NF-kappa B-dependent transcriptional activity. Because of the similarity between HIV and Ras-Raf-induced NF-kappa B activation in monocytic cells, we next tested whether HIV-induced NF-kappa B activation was mediated by the Ras-Raf signal transduction pathway. Negative dominant forms of both Ras (Ras N17) and Raf (Raf 301) decreased the HIV- but not lipopolysaccharide-dependent NF-kappa B activation in U937 cells. Moreover, Raf-1 kinase activity was greater in HIV-infected than uninfected monocytic cells in in vitro kinase assays. Altogether, these results indicate that the Ras-Raf pathway is unregulated in HIV monocytic cells and participates in the virus-induced activation of NF-kappa B.
 ...
PMID:The Ras-Raf pathway is activated in human immunodeficiency virus-infected monocytes and particpates in the activation of NF-kappa B. 864 60

Through its action on macrophages, bacterial lipopolysaccharide (LPS) or endotoxin can trigger responses that are protective or injurious to the host. This review examines the effects of LPS on macrophages by following events from the cell surface to the nucleus. The involvement of protein tyrosine kinases, mitogen-activated protein kinases, protein kinase C, G proteins, protein kinase A, ceramide-activated protein kinase, and microtubules in this process are reviewed. At the nuclear level, rel, C/EBP, Ets, Egr, fos, and jun family members have been implicated in activation of LPS-inducible gene expression.
 ...
PMID:Endotoxin signal transduction in macrophages. 869 27

Preincubation of peripheral blood lymphocytes (PBL) from drug-free, healthy volunteers with either the protein tyrosine kinase inhibitor genistein (GNT, n = 10, final concentration 200 microM) or the protein kinase A activator dybutiryl-cyclic-AMP (cAMP, n = 11, final concentration 10 microM), resulted in a significant inhibition of natural killer cell activity (NKCA, expressed as percentage of specific chromium release). With the exception of 4 out of the 11 cAMP-treated samples, individual values for NKCA in the drug preincubated specimens were at least 20% below the same subject baseline activity; furthermore, NKC lytic function was non-detectable in 4 out of the 10 and in 1 out of the 11 samples pretreated with either GNT or cAMP, respectively. PBL preincubation with glutaraldehyde-fixed Gram-negative bacteria (GNB, n = 13, final GNB-to-effector cell ratio of 50 : 1) resulted in a statistically significant increase in NKCA (baseline (x +/- SD) of 21.6 +/- 16.4 and bacteria treated samples of 41.5 +/- 24.6, respectively, Student's paired t-test p < 0.05). At least a 20% increase in NKC lytic function over its own baseline value was recorded for 11 out of the 13 samples tested (Table 1). Preincubation with GNB and GNT (5 samples) not only blocked the immunostimulant effects of GNB (Student's paired t-test p < 0.05), but in most cases individual values for NKCA were similar to those recorded for GNT-only treated samples. Use of cAMP instead of GNT also blocked, but to a smaller extent, the GNB-produced increases in NKC lytic function (paired Student's t-test < 0.05). PBL preincubation with lipopolysaccharide (LPS, n = 11, final concentration 50 micrograms/ml) resulted in a statistically significant increase in NKCA (baseline (x +/- SD) of 20.7 +/- 14.1 and LPS treated samples of 39.2 +/- 18.5, respectively, Student's paired t-test < 0.05). At least a 20% increase in NKCA over its own baseline value was observed for each and everyone of the 11 samples studied (Table 2). Addition of LPS and GNT to the incubation mixture resulted not only in inhibition of the NKCA upmodulating LPS effects (Student's paired t-test p < 0.05), but each and everyone of the individual samples' NKCA were, in fact, significantly lower than their corresponding control baseline values and similar to those recorded for GNT-only treated samples. However, the use of LPS and cAMP (Table 2) produced less dramatic results, significant inhibition of LPS effect were recorded in only 2 samples (Nos 8 and 10), and individual NKCA in the remaining 3 specimens was significantly higher than the corresponding baseline value. Whereas experimental results obtained with GNT support the involvement of PTK-dependent pathways in the stimulation of human NKCA produced by GNB and LPS, cAMP experiments suggest modulation of PKA-dependent pathways as responsible for the decrease in NK lytic function produced by a number of chemicals involved in the pathophysiology associated with certain forms of stress, including septic shock. Further research in this area could help in the rational design of pharmacological approaches for the treatment of these conditions.
 ...
PMID:Activation of protein tyrosine kinase: a possible requirement for fixed-bacteria and lipopolysaccharide-induced increase in human natural killer cell activity. 873 58

There is currently much interest in the mechanisms of action of antiproliferative agents and their effects on cell cycle machinery. In the present study we examined the mechanisms of action of four unrelated agents known to inhibit proliferation of CSF-1-stimulated bone marrow-derived macrophages (BMM). We report that 8-bromo-cAMP (8Br-cAMP) and lipopolysaccharide (LPS) potently reduced CSF-1-stimulated cyclin D1 protein, and cyclin-dependent kinase (cdk) 4 mRNA and protein levels, while the inhibitory effects of the Na+/ H+ antiport inhibitor 5-(N',N'-dimethyl) amiloride (DMA) and interferon gamma (IFN gamma ) were only weak. All agents repressed CSF-1-stimulated retinoblastoma protein phosphorylation. Furthermore, 8Br-cAMP and to a lesser extent IFN gamma, also reduced CSF-1-stimulated levels of E2F DNA binding activity in a macrophage cell line, BAC1.2F5. An explanation for the different effects of the agents is that 8Br-cAMP and LPS were found to arrest BMM in early/mid-G1, while IFN gamma and DMA arrested cells in late G1 or early S phase. These data indicate that (1) different antiproliferative agents can arrest the same cell type at distinct checkpoints in G1 and (2) effects of antiproliferative agents on cell cycle machinery is linked to the position at which they arrest cells in G1.
 ...
PMID:Differential regulation of cell cycle machinery by various antiproliferative agents is linked to macrophage arrest at distinct G1 checkpoints. 876 Mar 1


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