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)

Interferon-gamma (IFN-gamma) modulates the expression of several cytokines by human monocytes at the transcriptional level. In view of these findings, we analyzed the effects of IFN-gamma on the expression of different transcription factors in activated human monocytes. Priming of human monocytes with IFN-gamma resulted in the down regulation of c-fos and c-jun mRNA in response to stimulation with lipopolysaccharide (LPS) compared to the effects of LPS alone. Not only was this effect observed at the mRNA level, but activator protein-1 (AP-1) DNA binding capacity was affected as well, A strong reduction was observed in the LPS-induced DNA-binding activity of AP-1 in the presence of IFN-gamma. LPS-stimulated monocytes showed an increased expression of p105 mRNA, the precursor of the p50 subunit of the transcription factor nuclear factor-kappa B (NF-kappa B), while no effect was noticed on the expression of p65 mRNA. In contrast, IFN-gamma priming did not affect the expression of p105 transcripts but enhanced the expression of p65 mRNA (two-fold). Priming with IFN-gamma followed by LPS stimulation resulted in a further increase in the expression of p65 mRNA. This was due to an increase in the half-life of p65 mRNA (75 vs 150 minutes). Electrophoretic mobility shift assays (EMSAs) demonstrated that unstimulated monocytes predominantly expressed p50 NF-kappa B. Stimulation with LPS or IFN-gamma resulted in the expression of p50 and p65 subunits, while the combination of IFN-gamma plus LPS caused a further increase in the expression of NF-kappa B. With Western blotting, it was shown that nuclear extracts from monocytes contained p50 and p65 protein in response to LPS and IFN-gamma stimulation. However, the combined stimulation did not result in enhanced p50 and p65 protein expression. The effects of IFN-gamma on the transcription factors were specific, since no change was observed in the expression of NF-IL-6 or I kappa B alpha, the inhibitor of NF-kappa B. We conclude that the effects of IFN-gamma on the expression of the transcription factors AP-1 and NF-kappa B may be important for the modulatory effects of IFN-gamma on the cytokine expression in activated human monocytes.
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PMID:Interferon-gamma modulates the lipopolysaccharide-induced expression of AP-1 and NF-kappa B at the mRNA and protein level in human monocytes. 864 46

Nitric oxide (NO), an intercellular messenger in the brain, has been implicated in both neuronal plasticity and neurotoxicity. It has been suggested that NO can activate the DNA binding activity of nuclear factor kappaB (NF-kappaB) family proteins in some cell types while having an inhibitory effect in others. In this study we have investigated the effect of acute NO in primary neuronal cultures of rat striatum using immunohistochemistry. Exposure of neurones to the NO-mimetic S-nitroso-n-acetylpenicillamine (SNAP; 200 microM) and to bacterial lipopolysaccharide (LPS; 10 microg/ml) for 30 min increased nuclear protein expression of the p50 subunit of NF-kappaB. SNAP also enhanced nuclear protein expression of the p65 subunit of NF-kappaB. Simultaneously, the cytoplasmic expression of phosphorylated inhibitory protein IkappaB alpha was dramatically increased by SNAP (200 microM), LPS (10 microg/ml), and kainate (50 microM) treatment. In the adult rat, stimulation with NOR-3 (2 mg/kg), a NO donor, increased NF-kappaB DNA binding activity in the striatum after 45 min. Because glucocorticoids inhibit NF-kappaB activity, primary cultures were pretreated with dexamethasone (50 microM) before SNAP, LPS, and kainate treatment, and the effect on the protein expression level of the individual subunits p50 and p65 present in the classical form of the transcription factor NF-kappaB was assessed. Dexamethasone pretreatment resulted in a marked reduction of p65 protein in striatal neurones after SNAP, LPS, and kainate, whereas p50 expression was reduced by dexamethasone pretreatment only after an LPS stimulus. This study indicates that NO-releasing compounds can directly induce nuclear NF-kappaB subunit expression in rat striatum and that glucocorticoids selectively inhibit p65 subunit expression following exposure to NO.
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PMID:Activation of nuclear factor kappaB by nitric oxide in rat striatal neurones: differential inhibition of the p50 and p65 subunits by dexamethasone. 1038 88

Interleukin (IL)-1beta-deficient (IL-1beta(-/-)) mice were assessed for cytokine production during pregnancy. A significant reduction in nuclear factor (NF)-kappaB p65 protein content was observed in the uteri and spleens of pregnant IL-1beta(-/-) mice, as demonstrated by immunohistochemistry and Western immunoblot analysis. In addition, electromobility gel shift assay revealed less DNA binding activity of NF-kappaB p65-containing complex in pregnant IL-1beta(-/-) mice. To investigate differences in cytokine production regulated by NF-kappaB, the levels of tumor necrosis factor-alpha, macrophage inflammatory protein-1alpha, and interferon-gamma were measured in the uterine wall, spleen homogenates, and spleen cell cultures obtained from pregnant mice. Endocervical administration of lipopolysaccharide (LPS) increased cytokine levels in both wild-type (IL-1beta(+/+)) and IL-1beta(-/-) animals, but in IL-1beta(-/-) mice this response was 50-75% lower. Splenocytes from nonpregnant mice exhibited decreased LPS-induced cytokine production when primed in vitro with progesterone. This suppression was 25% greater in IL-1beta(-/-) than in IL-1beta(+/+) mice. These data suggest that constitutive NF-kappaB p65 protein synthesis is regulated by IL-1beta, particularly during pregnancy.
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PMID:Interleukin-1beta deficiency results in reduced NF-kappaB levels in pregnant mice. 1064 48

Increased levels of inflammatory cytokines such as interleukin (IL)-1 and IL-8 occur in the bronchoalveolar lavage fluid in various lung diseases. Cytokine gene expression is controlled by transcription factors such as nuclear factor-kappaB (NF-kappaB) which can be activated by a number of stimuli including the oxidants prevent. It was hypothesized that lipopolysaccharide (LPS)-induced IL-1beta secretion may be modulated by the intracellular thiol redox status of the cells. The effect of the antioxidant compound, N-acetyl-L-cysteine (NAC), on IL-1beta release and regulation of NF-kappaB in a human myelo-monocytic cell line (THP-1) differentiated into macrophages was studied. LPS (10 microg x mL(-1)) increased IL-1beta release at 24 h compared to control levels (p<0.001). NAC (5 mM) also enhanced LPS-induced IL-1beta release from THP-1 cells (p<0.001). In addition, treatment of cells with cycloheximide, an inhibitor of protein synthesis, inhibited the NAC-mediated IL-1beta release. Under the same conditions, NF-kappaB binding was activated by LPS and NAC increased this LPS-mediated effect. Western blot analysis revealed that NAC treatment leads to an increase in p50 and p65 protein synthesis. These data indicate that N-acetyl-L-cysteine modulates interleukin-1kappa release by increasing levels of the homo- and heterodimeric forms of nuclear factor-kappaB.
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PMID:Regulation of lipopolysaccharide-mediated interleukin-1beta release by N-acetylcysteine in THP-1 cells. 1115 95

The Janus kinase (JAK) family of protein tyrosine kinases are activated in response to a wide variety of external stimuli. Here we have investigated whether the janus kinase 2 (JAK2) is involved in the induction of nitric oxide synthase type II (iNOS) expression in a mouse fetal skin dendritic cell line (FSDC). In FSDC the expression of iNOS protein and nitric oxide production, in response to the lipopolysaccharide (LPS) stimulus (5 microg/ml), is inhibited by the specific inhibitor of the JAK2, tyrphostin B42 with an half maximal inhibitory concentration (IC(50)) of 9.65 microM. The antioxidant compound pyrrolidinedithiocarbamate (PDTC) inhibits both the nitrite production with an IC(50) of 16.6 microM and the iNOS protein expression in FSDC. In addition, LPS induces the activation of NF-kappa B, and tyrphostin B42 prevents the degradation of the cytosolic factor I kappa B-alpha and blocks the translocation of the NF-kappa B p65 protein subunit into the nucleus. These results indicate that the JAK family of protein kinases and the transcription factor NF-kappa B are involved in the induction of iNOS protein expression in FSDC stimulated with LPS.
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PMID:LPS induction of I kappa B-alpha degradation and iNOS expression in a skin dendritic cell line is prevented by the janus kinase 2 inhibitor, Tyrphostin b42. 1117 37

As an attempt to search for bioactive natural products exerting antiinflammatory activity, we have evaluated the effects of the methanol extract from the aerial parts of Saururus chinensis (LOUR.) BAILL (Saururaceae) on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) release by the macrophage cell line RAW 264.7. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased PGE(2) release. Consistent with these observations, the protein and mRNA expression level of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 was inhibited by MeOH extracts of the aerial part of S. chinensis (SCM) in a dose-dependent manner. Furthermore, SCM inhibited the LPS-induced DNA binding activity of nuclear factor-kappaB (NF-kappaB), which was associated with decreased p65 protein levels in the nucleus. These results suggest that SCM inhibits LPS-induced iNOS and COX-2 expression by blocking NF-kappaB activation.
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PMID:Inhibition of methanol extract from the aerial parts of Saururus chinensis on lipopolysaccharide-induced nitric oxide and prostagladin E2 production from murine macrophage RAW 264.7 cells. 1267 29

Alcoholic liver disease is associated with hepatic iron accumulation, and iron supplementation exacerbates alcoholic liver disease, suggesting the pathogenic role of iron in alcoholic liver disease. We have tested a hypothesis that iron plays a signaling role in activation of redox-sensitive nuclear factor-kappa B (NF-kappaB) and that increased iron content results in heightened expression of proinflammatory cytokines in Kupffer cells because of this signaling. In cultured Kupffer cells isolated from normal rats, treatment with a lipophilic iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one (L1), markedly reduced lipopolysaccharide (LPS)-induced NF-kappaB activation and expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6. Kupffer cells, isolated from rats with experimentally induced alcoholic liver disease, had significant increases in nonheme iron content, NF-kappaB binding, and mRNA expression for TNF-alpha and macrophage inflammatory protein-1. Ex vivo L1 treatment normalized all these parameters. Addition of ferrous iron to cultured normal rat Kupffer cells increased I-kappa B kinase (IKK) activity at 15 min and NF-kappaB binding at 30 min. L1 pretreatment completely abrogated both effects. Moreover, the iron treatment increased TNF-alpha release and TNF-alpha promoter activity in a NF-kappaB-dependent manner. Ferrous iron also transiently decreased cytoplasmic I-kappa B-alpha (IkappaB-alpha), with concomitant increases in nuclear p65 protein and DNA binding of p65/p50. Taken together, these results support the existence of iron-dependent signaling for activation of IKK/NF-kappaB in Kupffer cells, and this iron signaling serves as a target for a potential priming effect for the pathogenesis of experimental alcoholic liver disease.
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PMID:Iron-dependent activation of NF-kappaB in Kupffer cells: a priming mechanism for alcoholic liver disease. 1295 94

In the present study, the effects of various triterpenoids isolated from the stem bark of Cussonia bancoensis, namely, ursolic acid ( 1), 23-hydroxyursolic acid ( 2), 3-O-alpha- L-arabinopyranosyl-23-hydroxyursolic acid (3), and 3-O-beta-D-glucopyranosyl-23-hydroxyursolic acid ( 4) were evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E (2) (PGE (2)) release by the macrophage cell line RAW 264.7. Of the tested triterpenoids, 23-hydroxyursolic acid ( 2) was found to be the most potent inhibitor of NO production, and also significantly reduced PGE (2) release. Consistent with these observations, the protein and mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 enzymes were inhibited by 23-hydroxyursolic acid ( 2) in a concentration-dependent manner. Furthermore, 23-hydroxyursolic acid ( 2) inhibited the LPS-induced DNA binding activity of nuclear factor- kappaB (NF- kappaB), which was associated with a decrease of p65 protein levels in the nucleus. These results suggest that the 23-hydroxyursolic acid-mediated inhibition of iNOS and COX-2 expression, via blocking NF- kappaB activation, may mechanistically responsible for the anti-inflammatory effects of Cussonia bancoensis stem bark in vitro.
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PMID:In vitro anti-inflammatory activity of 23-hydroxyursolic acid isolated from Cussonia bancoensis in murine macrophage RAW 264.7 cells. 1538 88

The anti-inflammatory effects of caffeic acid (CA), caffeic acid methyl ester (CM) and di-O-acetylcaffeic acid (DAC) were investigated in rats using the carrageenin-induced edema model and the antinociceptive effects of these compounds were also assessed in mice by means of the acetic acid-induced abdominal constriction test and hot plate test. CM (10mg/kg, p.o.) showed the most potent anti-inflammatory and antinociceptive effects in these animal models. To investigate the mechanism of the anti-inflammatory action, we examined the effects of these compounds on the lipopolysaccharide (LPS)-induced NO and PGE2 responses in the murine macrophage cell line, RAW 264.7. Our data indicate that CM is the most potent inhibitor of NO and PGE2 production and it also significantly decreased tumor necrosis factor-alpha (TNF-alpha) release. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 were found to be inhibited by CM in a dose-dependent manner. Furthermore, CM inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS, which was associated with the prevention of the degradation of the inhibitor kappaB, and subsequently with decreased p65 protein levels in the nucleus. Taken together, our data indicate that the anti-inflammatory properties of CM might result from the inhibition of iNOS, COX-2 and TNF-alpha expression through the down-regulation of NF-kappaB binding activity.
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PMID:Anti-inflammatory effect of caffeic acid methyl ester and its mode of action through the inhibition of prostaglandin E2, nitric oxide and tumor necrosis factor-alpha production. 1554 79

The anti-inflammatory effects of the methanol extract of the roots of Morinda officinalis (MEMO) (Rubiaceae) were evaluated in-vitro and in-vivo. The effects of MEMO on lipopolysaccharide (LPS)induced responses in the murine macrophage cell line RAW 264.7 were examined. MEMO potently inhibited the production of nitric oxide (NO), prostaglandin E2 and tumour necrosis factor-alpha (TNF-alpha) in LPS-stimulated RAW 264.7 macrophages. Consistent with these results, the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein level, and of iNOS, COX-2 and TNF-alpha at the mRNA level, was also inhibited by MEMO in a concentration-dependent manner. Furthermore, MEMO inhibited the nuclear factor kappa B (NF-kappaB) activation induced by LPS, and this was associated with the prevention of degradation of the inhibitor kappaB (IkappaB), and subsequently with attenuated p65 protein in the nucleus. The anti-inflammatory effect of MEMO was examined in rats using the carrageenan-induced oedema model. The antinociceptive effects of MEMO were assessed in mice using the acetic acid-induced abdominal constriction test and the hot-plate test. MEMO (100, 200 mg kg-1 per day, p.o.) exhibited anti-inflammatory and antinociceptive effects in these animal models. Taken together, the data demonstrate that MEMO has anti-inflammatory and antinociceptive activity, inhibiting iNOS, COX-2 and TNF-alpha expression by down-regulating NF-kappaB binding activity.
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PMID:In-vitro and in-vivo anti-inflammatory and antinociceptive effects of the methanol extract of the roots of Morinda officinalis. 1590 50


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