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)

Hepatocytes and intrahepatic progenitor cells (oval cells) have similar responses to most growth factors but rarely proliferate together. Oval cells constitute a reserve compartment that is activated when hepatocyte proliferation is inhibited. Interferon gamma (IFN-gamma) increases in liver injury that involves oval cell responses, but it is not upregulated during liver regeneration after partial hepatectomy. Based on these observations, we used well-characterized lines of hepatocytes (AML-12 cells) and oval cells (LE-6 cells) to investigate the potential mechanisms that regulate differential growth responses in hepatocytes and oval cells. We show that IFN-gamma blocks hepatocyte proliferation in vivo, and that in combination with either tumor necrosis factor (TNF) or lipopolysaccharide (LPS), it causes cell cycle arrest in hepatocytes but stimulates oval cell proliferation in cultured cells. The hepatocyte cell cycle arrest is reversible, is p53-independent, and is not associated with apoptosis. Treatment of AML-12 hepatocytes with IFN-gamma/LPS or IFN-gamma/TNF, but not with individual cytokines, induced NO synthase and generated NO, while similarly treated oval cells produced little if any NO. Generation of NO by an NO donor reproduced the inhibitory effect of the cytokine combinations on AML-12 cell replication, while NO inhibitors abolish the replication deficiency. In conclusion, we propose that IFN-gamma, in conjunction with TNF or LPS, can both inhibit hepatocyte proliferation through the generation of NO and stimulate oval cell replication. The response of hepatocytes and oval cells to cytokine combinations may contribute to the differential proliferation of these cells in hepatic growth processes.
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PMID:Differential regulation of rodent hepatocyte and oval cell proliferation by interferon gamma. 1579 32

The effect of lipopolysaccharide on doxorubicin-induced cell death was studied by using mouse RAW 264.7 macrophage cells. Pretreatment with lipopolysaccharide at 10 ng/mL prevented doxorubicin-induced cell death and the inhibition was roughly dependent on the concentration of lipopolysaccharide. Posttreatment with lipopolysaccharide for 1 hour also prevented doxorubicin-induced cell death. Lipopolysaccharide inhibited DNA fragmentation and caspase-3 activation in doxorubicin-treated RAW 264.7 cells, suggesting the prevention of doxorubicin-induced apoptosis. Lipopolysaccharide did not significantly inhibit doxorubicin-induced DNA damage detected by single-cell gel electrophoresis (comet) assay. Lipopolysaccharide definitely inhibited the stabilization and nuclear translocation of p53 in doxorubicin-treated RAW 264.7 cells. Lipopolysaccharide, as well as being an inhibitor of p53, abolished doxorubicin-induced apoptosis. Therefore, p53 was suggested to play a pivotal role in the prevention of doxorubicin-induced apoptosis in RAW 264.7 cells by lipopolysaccharide.
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PMID:Lipopolysaccharide prevents doxorubicin-induced apoptosis in RAW 264.7 macrophage cells by inhibiting p53 activation. 1604 48

Neuroinflammation has been suggested to play an integral role in the pathophysiology of various neurodegenerative diseases. Bacterial lipopolysaccharide (LPS) endotoxins are general activators of immune-cells, including microglial cells, which induce expression of pro-inflammatory factors. The aim of this study was to characterize neurodegenerative effects of exposure to LPS, derived from Salmonella abortus equi bacteria, in an in vitro brain slice culture system. Quasi-monolayer cultures were obtained using roller-drum incubations of hippocampal slices from neonatal Sprague Dawley rats for three weeks. Microglia/macrophages were identified in the monolayer cultures by CD11b immunostaining, while neuronal populations identified included N-methyl-D-aspartate (NMDA-R1) receptor immunoreactive pyramidal neurons and smaller GABA-immunoreactive cells. Following exposure to LPS (100 ng/ml) an increased density of CD11b positive cells was found in the cultures. In addition, the LPS exposure produced a concentration-dependent loss of the NMDA-R1 immunoreactive neurons in the cultures which was substantial at 100 ng/ml LPS. The loss of NMDA-R1 cells was apparent already after 24 h exposure to LPS and seemed to be primarily due to necrotic-like cell death. However, a continued loss of cells was found when cultures were analyzed at 72 h, concomitant with an increase in the expression of p53 in the NMDA-R1 cells and TUNEL labeling of a few cells. Also the number of GABA-immunoreactive cells decreased rapidly and to a substantial extent after 24 h exposure to LPS, with a continued decrease up to 72 h. The findings show that Salmonella LPS increases the density of CD11b positive cells and acts as a potent neurotoxin in hippocampal roller-drum slice cultures. The LPS-induced neurodegeneration has both necrotic- and apoptotic-like properties and appears to be non-selective, affecting both pyramidal and GABA neurons. LPS-induced neurotoxicity in slice cultures may be a useful system to study processes involved in inflammatory-mediated neurodegeneration.
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PMID:Salmonella lipopolysaccharide (LPS) mediated neurodegeneration in hippocampal slice cultures. 1637 15

Dendritic cells (DC) are now recognized as the most potent professional antigen presenting cells (APC). Several studies on cancer immunotherapy using different approaches to induce cytotoxic T lymphocytes (CTL) in vivo recognizing tumor-associated antigens have been reported. However, the efficacy of immunotherapy in vivo may be limited by the local or systemic suppression of CTL generation or function. To explore the ability of lipopolysaccharide (LPS) stimulated human monocyte-derived DC involved in activity of autologous CD4(+)CD25(+) T cells, HLA-A2 restricted p53(264 - 272) peptide was used as tumor antigen, DC generated with LPS (DC-LPS(+)) or without LPS (DC-LPS(-)) were co-cultured with autologous T cells respectively. The results showed that CD4(+)CD25(+) T cell population in the DC-LPS(+) activated T cells was lower than that in the DC-LPS(-) activated T cells. This finding suggest that the relationship between DC-LPS(+) and population of CD4(+)CD25(+) T cells exists and this property may contribute to regulation of T cell responses to tumor-associated antigens.
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PMID:Role of LPS-stimulated human monocyte-derived dendritic cells in the modulation of autologous CD4+ CD25+ T Cell activation. 1640 82

Btk is critical for B cell development and proliferation. Mice lacking Btk have a defect in B cell development, resulting in a loss of mature B cells and decreased proliferative responses following B cell receptor cross-linking. In contrast, mice deficient in the tumor suppressor p53 display increases in developing B cell populations in the bone marrow. To investigate the potential role of p53 in Btk-dependent B cell development and function, we generated mice doubly-deficient in p53 and Btk. Btk/p53-deficient mice showed an increase in splenic B220+ cell numbers compared with Btk-deficient mice, although there was no recovery in B cell subset differentiation. In contrast to the lack of recovery of B cell development, there was a recovery in lipopolysaccharide and anti-immunoglobulin M (IgM) plus interleukin-4-induced proliferation of Btk/p53-deficient B cells, although there was no recovery to anti-IgM stimulation alone. Thus, p53 promotes B cell expansion and proliferation, but p53 deficiency cannot compensate for Btk deficiency in the development of B cell subsets.
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PMID:p53 regulates Btk-dependent B cell proliferation but not differentiation. 1646 47

Since inducible nitric oxide synthase (iNOS) and proximal tubule injury are known to be critical determinants of lipopolysaccharide (LPS)-induced renal failure, the role of nitric oxide (NO) in proximal tubule cell apoptosis was examined. An 18-h treatment with a combination of LPS (5 microg/ml) and interferon-gamma (IFN-gamma, 100 units/ml) synergistically induced iNOS and produced a 20-fold increase in NO generation in the TKPTS murine proximal tubule cell line. NO generation by LPS + IFN-gamma was blocked by a specific iNOS blocker, L-N6-(1-iminoethyl)-lysine (L-NIL, 1 mM). To assess the role of iNOS-derived NO in proximal tubule cell apoptosis, annexin V- and propidium iodide-labeled cells were analyzed by flow cytometry. Neither the induction of iNOS nor its inhibition produced significant apoptotic cell death in TKPTS cells. Two exogenous NO donors were used to examine the role of NO more directly in proximal tubule apoptosis. Although both sodium nitroprusside (SNP), an iron-containing, nitrosonium cation donor, and S-nitroso-N-acetylpenicillamine (SNAP), a noniron-containing, NO generator, produced a concentration-dependent increase in NO generation, only SNP increased apoptotic cell death in TKPTS cells (5.9 +/- 0.7% in control cells vs. 21.6 +/- 3.8% in SNP [500 microM]-treated cells; n = 4-9; p < 0.01). SNP-mediated tubule cell apoptosis was not dependent on the activation of caspases or p53 but was possibly related to the generation of reactive oxygen species by SNP. Thus, in TKPTS cells induction of iNOS and generation of NO by LPS does not lead to tubular epithelial cell death.
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PMID:Inducible nitric oxide synthase and apoptosis in murine proximal tubule epithelial cells. 1655 43

To improve the understanding of the molecular mechanisms whereby lipopolysaccharide (LPS) affects the immature brain, global gene expression following LPS exposure was investigated in neonatal rats. Brains (n = 5/time point) were sampled 2, 6, and 72 h after LPS and compared with age-matched controls. The mRNA from each brain was analyzed separately on Affymextrix GeneChip Rat Expression Set 230. The number of genes regulated after LPS were 847 at 2 h, 1564 at 6 h, and 1546 genes at 72 h. Gene ontology analysis demonstrated that, at both 2 and 6 h after LPS, genes associated with protein metabolism, response to external stimuli and stress (immune and inflammatory response, chemotaxis) and cell death were overrepresented. At 72 h, the most strongly regulated genes belonged to secretion of neurotransmitters, transport, synaptic transmission, cell migration, and neurogenesis. Several pathways associated with cell death/survival were identified (caspase-tumor necrosis factor alpha [TNF-alpha]-, p53-, and Akt/phosphatidylinositol-3-kinase (PI3 K)-dependent mechanisms). Caspase-3 activity increased and phosphorylation of Akt decreased 8 h after peripheral LPS exposure. These results show a complex cerebral response to peripheral LPS exposure. In addition to the inflammatory response, a significant number of cell death-associated genes were identified, which may contribute to increased vulnerability of the immature brain to hypoxia-ischemia (HI) following LPS exposure.
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PMID:Effect of lipopolysaccharide on global gene expression in the immature rat brain. 1686 97

The p53 protein is a sequence-specific DNA-binding factor that can induce apoptosis or activate genes whose dysregulation is involved in cancer. By using serial analysis of gene expression technique, p53-induced genes (PIGs) have been identified, one of which was lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) factor (LITAF/PIG7). LITAF regulates the transcription of cytokines such as TNF-alpha. To further elucidate the role of p53 in LITAF expression, LITAF promoter activity was carefully dissected. In this study, we found that the element required for transcriptional activity is mainly located in the region from -990 to -500 of the LITAF promoter; the specific site required for p53 protein-DNA binding is located between -550 and -500. We also found that transient transfection of either a p53 short DNA sequence, called p53LFB12, or its corresponding 7-amino-acid synthetic peptide from amino acids 164 to 170 (K164Q165S166Q167H168M169T170), named p53pep164, significantly reduced LITAF promoter activity to 15% in p53-null H1299 cells. Transfection of p53pep164 into H1299 cells significantly down-regulated LPS-induced LITAF expression as well. Furthermore, transfection of p53pep164 into human monocytes resulted in down-regulation of nine proinflammatory cytokines, including TNF-alpha. We also found that the LPS-activated p53 is a short-lived protein, and that p53-orchestrated apoptosis occurs shortly after the initiation stage following LPS stimulation and lasts a short time. Once p53 levels return to baseline, the p53-mediated inhibition of LITAF is released, and LITAF-mediated cytokine production can proceed. The present finding proposes a novel link between p53 and the inflammatory processes and highlights potential interventional approaches to control p53-associated inflammatory processes.
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PMID:p53 short peptide (p53pep164) regulates lipopolysaccharide-induced tumor necrosis factor-alpha factor/cytokine expression. 1728 68

Macrocyclic trichothecene mycotoxins produced by indoor air molds potentially contribute to symptoms associated with damp building illnesses. The purpose of this investigation was to determine (1) the kinetics of nasal inflammation and neurotoxicity after a single intranasal instillation of roridin A (RA), a representative macrocyclic trichothecene; and (2) the capacity of lipopolysaccharide (LPS) to modulate RA's effects. C57Bl/6 female mice were intranasally instilled once with 50 mul of RA (500 mug/kg body weight [bw]) in saline or saline only and then nose and brain tissues were collected over 72 h and processed for histopathologic and messenger RNA (mRNA) analysis. RA-induced apoptosis specifically in olfactory sensory neurons (OSNs) after 24 h postinstillation (PI) causing marked atrophy of olfactory epithelium (OE) that was maximal at 72 h PI. Concurrently, there was marked bilateral atrophy of olfactory nerve layer of the olfactory bulbs (OBs) of the brain. In the ethmoid turbinates, upregulated messenger RNA (mRNA) expression of the proapoptotic gene FAS and the proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-6, IL-1, and macrophage inhibitory protein-2 was observed from 6 to 24 h PI, whereas expression of several other proapoptotic genes (PKR, p53, Bax, and caspase-activated DNAse) was detectable only at 24 h PI. Simultaneous exposure to LPS (500 ng/kg bw) and a lower dose of RA (250 mug/kg bw) magnified RA-induced proinflammatory gene expression, apoptosis, and inflammation in the nasal tract. Taken together, the results suggest that RA markedly induced FAS and proinflammatory cytokine expression prior to evoking OSN apoptosis and OE atrophy and that RA's effects were augmented by LPS.
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PMID:Neurotoxicity and inflammation in the nasal airways of mice exposed to the macrocyclic trichothecene mycotoxin roridin a: kinetics and potentiation by bacterial lipopolysaccharide coexposure. 1748 19

It is known that the nervous system significantly attenuates systemic inflammatory responses through the parasympathetic nervous system. Furthermore, it has been reported that the alpha 7 subunit of a nicotinic acetylcholine receptor is required for a cholinergic inhibition against cytokine synthesis in a macrophage. As antigen-presenting cells (APCs) play a central role in the generation of primary T cell responses and the maintenance of immunity, in this study, we investigated the expression level of nicotinic receptors of a p53-deficient APC cell line (JawsII) derived from a mouse bone marrow. We showed that stimulation of the JawsII cells with lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-alpha) led increase of CD80 and CD86 expression while diminishment of the surface nicotinic receptor. On the other hand, stimulation of nicotinic receptor had no effect on these phenomena. Furthermore, we examined the ability of the cells to release cytokine when stimulated with both nicotine and LPS and showed that the stimulation with LPS augmented the secretion of IL-1a, IL-1b, IL-6, and TNF-alpha. These results suggested that nicotinic stimulation had no effect on the diminishment of alpha 7 nicotinic acetylcholine receptor on JawsII cells by LPS stimulation.
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PMID:Inflammatory cytokines decrease the expression of nicotinic acetylcholine receptor during the cell maturation. 1962 24


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