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 putative new interleukin (IL)-1 family member IL-1F8 (IL-1eta, IL-1H2) has been shown recently to activate mitogen activated protein kinases (MAPKs), extracellular signal-regulated protein kinase (ERK1/2) and c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NFkappa B) via a mechanism that requires IL-1Rrp2 expression in cell lines. The aim of this study was to test the hypothesis that IL-1F8 contributes to brain inflammation and injury, by studying its expression and actions in the different cell types of the mouse brain in culture. Messenger RNA for IL-1F8 was detected in neurons and glia (microglial cells, oligodendrocytes progenitor cells and to a lesser extent astrocytes) by RT-PCR. Bacterial lipopolysaccharide (LPS) had no effect on IL-1F8 mRNA levels in mixed glial cultures. Recombinant mouse IL-1beta induced strong activation of ERK1/2, p38, JNK and NFkappa B, and significant release of IL-6 and PGE2, which was blocked by IL-1ra. In contrast, recombinant mouse IL-1F8 did not influence any of these parameters. These results demonstrate that CNS cells may be a source of IL-1F8, but the failure of LPS to modulate IL-1F8 mRNA expression, and of recombinant IL-1F8 to induce any of the classical IL-1 responses, suggest that this cytokine has restricted activities in the brain, or that it may act via alternative pathway(s).
 ...
PMID:The interleukin-1-related cytokine IL-1F8 is expressed in glial cells, but fails to induce IL-1beta signalling responses. 1574 24

We examined the modifying effects of a Kunitz trypsin inhibitor (KTI) and a Bowman-Birk trypsin inhibitor (BBI), purified from soybean, as intraperitoneal (i.p.) injection and dietary supplements on bacterial lipopolysaccharide (LPS)-induced lethality in mice. We initially examined the suppressing effects of i.p. injection of KTI (50 mg/kg) and BBI (50 mg/kg) on LPS-induced lethality after i.p. injection of LPS. Furthermore, groups of female C57BL/6 were fed a basal diet (control group) or the basal diet supplemented with KTI (50 g/kg) or BBI (50 g/kg). Here, we show that i.p. and daily oral administration of KTI, but not BBI, caused a significant reduction of the LPS-induced lethality; that LPS significantly induced plasma TNF-alpha, IL-1beta, and IL-6 levels in mice after LPS challenge; that concomitant administration of KTI, but not BBI, inhibits the LPS-induced plasma levels of these cytokines; and that KTI, but not BBI, suppressed LPS-induced upregulation of cytokine expression through suppression of phosphorylation of three mitogen-activated protein (MAP) kinase pathways, ERK1/2, JNK, and p38, in peritoneal macrophages. These data allow us to speculate that i.p. injection and dietary supplementation of a soybean KTI may play a role as a potent anti-inflammatory agent by inhibiting activation of MAP kinases, leading to the suppression of cytokine expression.
 ...
PMID:Dietary supplementation of soybean kunitz trypsin inhibitor reduces lipopolysaccharide-induced lethality in mouse model. 1583 10

We sought to determine if hypertonic saline (HTS) impacted alveolar macrophage (AM) activation and intracellular inflammatory gene signaling in a model of systemic inflammation. Rats received an intravenous administration of 4 mL/kg of 7.5% HTS or L-lactate lactated Ringer's (L-LR). They were simultaneously treated with an intraperitoneal injection of zymosan, which induces noninfectious systemic inflammation. AM were harvested by bronchoalveolar lavage 24 h after treatment. AM activation was analyzed by measurement of baseline and lipopolysaccharide (LPS)-induced TNF-alpha production. Intracellular signaling was analyzed for activation of the mitogen-activated protein kinases (MAPKs): ERK1/2, JNK, and p38. AM from HTS-treated rats produced less TNF-alpha than from L-LR-treated rats (927 +/- 335 pg/mL [SEM] vs. 3628 +/- 783 pg/mL [SEM], P = 0.001) and were also less responsive to LPS (4444 +/- 86 pg/mL [SEM] vs. 6666 +/- 91 pg/mL [SEM], P = 0.058). However, there was no difference in MAPK activation. In vivo HTS prevents excessive AM activation during systemic inflammation. This suppression is mediated through alternate pathways and does not induce the classic MAPK signaling cascade.
 ...
PMID:Hypertonic saline modulates innate immunity in a model of systemic inflammation. 1583 13

Sugiol is a diterpene which was isolated and purified from alcohol extracts of the bark of Calocedrus formosana Florin (Cupressaceae). Although sugiol has low inhibitory activity against the DPPH radical, it could effectively reduce intracellular reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-stimulated macrophages. The present study investigated the potential anti-inflammatory activity of sugiol, and the relationship between signal transduction and inflammatory cytokines in vitro. A dose of 30 microM of sugiol was effectively inhibitory for proIL-1beta, IL-1beta and TNF-alpha production, suggesting that sugiol is bioactive against inflammation. Moreover, sugiol reveals a capacity for suppressing the activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) activated by LPS-stimulation in J774A.1 murine macrophages. A low dosage of 10 microM of sugiol completely inhibited ERK1/2 phosphorylation, while 30 microM effectively inhibited JNK1/2 and p38 phosphorylation in LPS-stimulated macrophages. In addition, sugiol significantly inhibited LPS-induced ROS production. Our studies suggest that sugiol's efficacy in inhibiting the inflammatory cytokines of IL-1beta and TNF-alpha could be attributed to a reduction of the ROS that leads to a decrease in the phosphorylation of MAPKs.
 ...
PMID:Anti-inflammatory activity of sugiol, a diterpene isolated from Calocedrus formosana bark. 1585 4

Decoy receptor 3 (DcR3), a soluble receptor in the tumor necrosis factor (TNF) receptor family, is known to inhibit apoptosis mediated by pro-apoptotic TNF family cytokines such as Fas ligand (FasL), TL1A, and LIGHT. Therefore, the regulation of DcR3 expression under certain pathophysiological conditions is of interest since the level of soluble DcR3 would most likely affect the homeostasis of cells and tissues. We found that human intestinal epithelial cell (IEC) lines (SW480, SW620, and HT29) could selectively increase DcR3 release in response to lipopolysaccharide (LPS) and that all the cells preferentially expressed Toll-like receptor 4 (TLR-4). LPS-induced DcR3 releases in IECs appeared to be via the activation of mitogen-activated protein kinases (MAPK) such as extracellular signal-regulated kinase 1 and 2 (ERK1/2) and c-Jun NH2-terminal protein kinase (JNK), and the transcription factor NF-kappaB. Moreover, the increased expression of DcR3 in appendix epithelia from patients with acute appendicitis was demonstrated. Taken together, the results indicated that DcR3 might play an important role in the human intestinal epithelium during acute inflammatory processes caused by endotoxin challenge.
 ...
PMID:Increased expression of soluble decoy receptor 3 in acutely inflamed intestinal epithelia. 1589 96

Garcinol, a polyisoprenylated benzophenone, from the fruit rind of Garcinia spp., has been shown to have anti-inflammatory and anticarcinogenic activities. To study its mechanism of action, we analyzed the effects of garcinol and its derivatives, including cambogin, garcim-1 and garcim-2, on arachidonic acid metabolism and nitric oxide (NO) synthesis in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages as well as in three intestinal cell lines. We also examined the effect of garcinol on cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), and related upstream signaling. At 1 microM, garcinol and its derivatives, added 1 h after LPS stimulation, significantly inhibited the release of arachidonic acid and its metabolites in macrophages; garcinol was the most effective, showing >50% inhibition. Similar inhibitory activity was also observed in intestinal cells, HT-29, HCT-116 and IEC-6 cells, showing 40-50% inhibition by 1 microM garcinol. In LPS-stimulated macrophages, garcinol inhibited the phosphorylation of cPLA2 without altering its protein level, and the effect was related to the inhibition of ERK1/2 phosphorylation. Garcinol inhibited NFkappaB activation and COX-2 expression only when it was added to the cells before LPS stimulation. Garcinol (1 microM) also significantly decreased iNOS expression and NO release from LPS-stimulated macrophages; this is probably due to the inhibition of the signal transducer and activator of transcription-1 (STAT-1), an upstream event in the activation of iNOS synthesis. The results suggest that garcinol modulates arachidonic acid metabolism by blocking the phosphorylation of cPLA2 and decreases iNOS protein level by inhibiting STAT-1 activation. These activities may contribute to the anti-inflammatory and anticarcinogenic actions of garcinol and its derivatives.
 ...
PMID:Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives. 1609 50

Tissue factor (TF) plays a critical role in the pathogenesis of disseminated intravascular coagulation (DIC) observed in patients with septic shock. Urinary trypsin inhibitor (UTI), a multivalent protease inhibitor, is currently used for treatment of patients with septic shock. This study was undertaken to determine whether UTI reduces LPS-induced coagulation abnormalities by inhibiting lipopolysaccharide (LPS)-induced expression of TF by monocytes. UTI inhibited LPS-induced increases in both TF activities and TF mRNA expression in monocytes without affecting the viability. Although activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and extracellular signal-regulated kinase (ERK)1/2 were shown to be critically involved in LPS-induced increases in TF activities in isolated monocytes, UTI inhibited phosphorylation of ERK1/2 and decreased expression of early growth response factor-1 (Egr-1) induced by LPS without affecting the activation of NF-kappaB and AP-1. UTI inhibited both the expression of TF mRNA in whole blood, increases in TF activities in mononuclear cells, and increases in serum levels of fibrin and fibrinogen degradation products (E) in rats given LPS without affecting the number of monocytes in the peripheral blood. Taken together these results strongly suggested that UTI might reduce LPS-induced coagulation abnormalities in rats by inhibiting TF expression in monocytes through inhibition of Egr-1 expression.
 ...
PMID:Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo. 2213 Oct 84

Bacterial lipopolysaccharide (LPS) activates the immune system and promotes inflammation via Toll-like receptor (TLR) 4, which regulates the synthesis and release of tumor necrosis factor (TNF)-alpha and other inflammatory cytokines. Previous studies have shown that the nucleoside adenosine suppresses LPS-stimulated TNF-alpha release in human UB939 macrophages by activating an adenosine A(3) receptor (A(3)AR) subtype on these cells. In this study, we examined the mechanism(s) underlying A(3)AR-dependent inhibition of TNF-alpha release in a mouse (RAW 264.7) cell line. Treatment of RAW 264.7 cells with LPS (3 mug/ml) increased TNF-alpha release, which was reduced in a dose-dependent manner by adenosine analogs N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) and R-phenylisopropyladenosine and reversed by selective A(3)AR blockade. The increase in TNF-alpha release was preceded by an increase in intracellular Ca(2+) levels. Inhibition of intracellular Ca(2+) release by IB-MECA, a selective agonist of the A(3)AR, or with BAPTA-AM, an intracellular Ca(2+) chelator, reduced LPS-stimulated TNF-alpha release. Activation of the A(3)AR or inhibition of intracellular Ca(2+) release also reduced LPS-stimulated nuclear factor-kappaB (NF-kappaB) activation and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Similar inhibition by A(3)AR was observed for LPS-stimulated inducible nitric-oxide synthase. These data support the contention that inhibition of LPS-stimulated release of inflammatory molecules, such as TNF-alpha and NO via the A(3)AR, involves suppression of intracellular Ca(2+)signaling, leading to suppression of NF-kappaB and ERK1/2 pathways.
 ...
PMID:Activation of the adenosine A3 receptor in RAW 264.7 cells inhibits lipopolysaccharide-stimulated tumor necrosis factor-alpha release by reducing calcium-dependent activation of nuclear factor-kappaB and extracellular signal-regulated kinase 1/2. 1618 54

In the present study, the effects of several triterpenes isolated from the leaves of Acanthopanax chiisanensis (Araliaceae), namely, chiisanoside, isochiisanoside, 22-hydroxychiisanoside and chiisanogenin (the aglycone of chiisanoside) were evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by the RAW 264.7 macrophage cell line. Of the triterpenes tested, chiisanoside was found to most potently inhibit NO and PGE2 production. In addition, chiisanoside significantly reduced the release of inflammatory cytokines like TNF-alpha and IL-1beta. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were found to be inhibited by chiisanoside in a concentration-dependent manner. Furthermore, chiisanoside inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS and this was associated with a reduction in p65 protein in the nucleus and with the phosphorylations of ERK1/2 and JNK MAP kinases. Taken together, our data indicate that the anti-inflammatory properties of chiisanoside might be the result from the inhibition of iNOS, COX-2, TNF-alpha and IL-1beta expression through the down-regulation of NF-kappaB binding activity.
 ...
PMID:Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide and cyclooxygenase-2 by chiisanoside via suppression of nuclear factor-kappaB activation in RAW 264.7 macrophage cells. 1620 46

CNS inflammation mediated by microglial activation can result in neuronal and glial cell death in a variety of neurodegenerative and demyelinating diseases. Minocycline, a second-generation tetracycline, has profound anti-inflammatory properties in the CNS mediated, in part, by inhibition of microglia. MAPK and nuclear factor-kappaB (NF-kappaB) activation are hallmarks of activated microglia and they are critical for the expression of many inflammatory mediators. In the present study, we investigated minocycline effects on activation of p38, c-Jun-N-terminal activated protein kinase (JNK) 1/2 and extracellular signal regulated kinase (ERK) 1/2 MAPKs and inhibitor alpha of NF-kappaB (IkappaBalpha) degradation in BV-2 and primary microglial cells. Our results demonstrate that minocycline has the ability to inhibit all MAPKs but these effects strongly depend on the stimulus used for MAPK activation. Minocycline significantly decreased activation of all lipopolysaccharide-stimulated MAPKs but it was without effect on MAPKs activated by H2O2. Minocycline inhibited JNK1/2 and ERK1/2 but not p38 when stimulated by 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate, indicating that minocycline affects only certain upstream signaling target(s) that are stimulus-specific. Our data also suggest that protein kinase C (PKC) inhibition may be partially involved in the minocycline mechanism of MAPK inhibition. In addition, minocycline attenuated lipopolysaccharide-stimulated degradation of IkappaBalpha implying a possible inhibitory role on NF-kappaB transcriptional activity.
 ...
PMID:Minocycline exerts inhibitory effects on multiple mitogen-activated protein kinases and IkappaBalpha degradation in a stimulus-specific manner in microglia. 1633 36


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