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 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

The present study tested the hypothesis that alveolar macrophages (AM) from patients with chronic obstructive pulmonary disease (COPD) release more pro-inflammatory and/or less anti-inflammatory mediators than those from smokers with normal lung function and never-smokers. AM were sorted by flow cytometry from bronchoalveolar lavage fluid in 13 patients with COPD (mean+/-SEM 67+/-2 yrs, forced expiratory volume in one second (FEV1) 61+/-4% reference), 16 smokers with normal lung function (55+/-2 yrs, FEV1 97+/-4% reference) and seven never-smokers (67+/-7 yrs, FEV1 94+/-4% reference). After sorting, AM were cultured (with and without lipopolysaccharide stimulation) after 4 h and 24 h, and the concentrations of leukotriene B4 (LTB4), transforming growth factor (TGF)-beta1 and tissue inhibitor of metalloproteinase (TIMP)-1 were quantified in the supernatant by ELISA. The production of reactive oxygen intermediates (ROI) in freshly isolated AM was determined by flow cytometry. LTB4 secretion and ROI production were not different between groups. In contrast, AM from COPD patients released significantly less TGF-beta1 and TIMP-1 than those from smokers with normal lung function and nonsmokers. In conclusion, these observations are compatible with reduced anti-inflammatory and anti-elastolytic capacity in chronic obstructive pulmonary disease, which is likely to contribute to the pathogenesis of the disease.
 ...
PMID:Decreased macrophage release of TGF-beta and TIMP-1 in chronic obstructive pulmonary disease. 1599 90

The maternal syndrome preeclampsia is characterized by a generalized inflammatory response with activation of circulating leukocytes and altered levels of inflammatory cytokines. We hypothesized that one potential source of inflammatory cytokines during preeclampsia is the circulating maternal monocytes. By using flow cytometry, we found that the spontaneous intracellular synthesis of IL-1beta, IL-6, and IL-8 in monocytes of preeclamptic women was higher than in normal pregnant and non-pregnant women. The highest levels of cytokines were detected in women with the most abnormal laboratory values. When stimulated with lipopolysaccharide (LPS), the percentage of IL-1beta+ monocytes was lower in preeclampsia (72.6% +/- 8.2 SEM) than in normal pregnancy (90.7% +/- 2 SEM) (P = 0.03) and non-pregnant women (92.5% +/- 1.4 SEM) (P = 0.04) suggesting that monocytes from preeclamptic patients cannot be further stimulated. These results indicate that maternal circulating monocytes represent a source of inflammatory cytokines during preeclampsia.
 ...
PMID:Monocytes of preeclamptic women spontaneously synthesize pro-inflammatory cytokines. 1633 93

Hypertonic saline (HTS) suppresses tumor cell-endothelial interactions by reducing integrin expression. This translates into reduced adhesion, migration and metastatic potential. This study determined the relative contributions of hyperosmolarity and sodium-specific hypertonicity on the inhibitory effects of HTS, the intracellular pH and sodium responses to HTS and the role of cytoskeletal remodeling in these changes. Human colonic tumor cells (LS174T) were exposed to lipopolysaccharide under isotonic, hypertonic, sodium-free (N-methyl-D-glucamine), hyperosmolar (mannitol or urea), disrupted cytoskeletal (10 microg/ml cytochalasin D) conditions or in the presence of 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Beta(1) integrin expression was measured flow-cytometrically. Intracellular sodium and pH were measured with confocal laser microscopic imaging. Statistical analysis was performed with analysis of variance, and P < 0.05 was considered significant. Data are represented as mean +/- SEM. Hypertonic exposure attenuated integrin expression (62.03 +/- 4.7% of control, P < 0.04). No discernible effect was observed with sodium-free or hyperosmolar solutions. HTS evoked a cellular alkalinization (by a mean 0.2 pH units) and an increase in cytosolic sodium concentration (by a mean 12.4 mM, P < 0.001) via upregulation of sodium-hydrogen exchange. Disassembly of actin microfilaments by cytochalasin D and antiporter inhibition with EIPA abrogated the effect of hypertonicity on integrin expression and intracellular sodium and pH (P < 0.05). HTS downregulates adhesion molecule expression via a hypertonic, sodium-specific, cytoskeletally mediated mechanism that involves activation of sodium-hydrogen exchange with associated changes in intracellular pH and sodium concentrations.
 ...
PMID:Hypertonic saline attenuates colonic tumor cell metastatic potential by activating transmembrane sodium conductance. 1698 62

Progenitor cell plasticity enhances positive remodeling of damaged tissue. We and others have previously shown that progenitor cells may limit apoptosis and modulate inflammation in part by the production of growth factors. However, recent studies suggest that progenitor cells senesce and lose their differentiation potential with increasing time in culture and passage. We hypothesize that murine bone marrow mesenchymal stem cells (MSCs) are cardioprotective against ischemia/reperfusion injury in the isolated perfused rat heart, and that passage number has an adverse effect on MSC activation and cardioprotection. Adult male and female Sprague-Dawley rat hearts were isolated, perfused via Langendorff model, and subjected to ischemia/reperfusion. Mouse MSCs were harvested, cultured, suspended in perfusate, and infused before global index ischemia. Hearts were assigned to controls or infusion with passage 3, 5, or 10 MSCs. In addition, MSCs in culture were stressed by hypoxia and increasing doses of endotoxin (lipopolysaccharide). Mesenchymal stem cell activation was determined by measuring vascular endothelial growth factor production with enzyme-linked immunosorbent assay. All data are reported as mean +/- SEM and were analyzed with 2-way analysis of variance. Differences are considered significant if P < 0.05. Passage 3 murine MSC infusion in hearts before ischemia reduced the depression of left ventricular developed pressure, attenuated the increase of end-diastolic pressure, and reduced the depression of +dP/dT and -dP/dT. However, the MSC protective effect disappeared in hearts infused with passage 5 and passage 10 MSCs. Although hypoxia and lipopolysaccharide resulted in significant activation of MSCs, passage 3 MSCs demonstrated significantly greater vascular endothelial growth factor release than passage 5 and 10 MSCs. Acute murine MSC infusion confers protection in isolated rat hearts. However, high passage number has an adverse effect on MSC activation and protection. This portends limited ex vivo expansion before possible therapeutic use.
 ...
PMID:High passage number of stem cells adversely affects stem cell activation and myocardial protection. 1711 32

The objectives of this study were to determine the presence of natural antibodies (NAb) in plasma and milk of individual dairy cows and to study the relation between NAb concentrations and energy balance (EB) and dietary energy source. Cows (n = 76) were fed a mainly glucogenic, lipogenic, or a mixture of both diets (50:50 dry matter basis) from wk 3 before the expected calving date until wk 9 postpartum. Diets were isocaloric (net energy basis) and equal in intestinal digestible protein. Blood and milk were sampled weekly. Liver biopsies were taken in wk -2, 2, 4, and 6 relative to calving. Data are expressed as LSM +/- SEM. The NAb titers are expressed as the (2)log values of the highest dilution giving a positive reaction. The NAb concentration in plasma binding either keyhole limpet hemocyanin (KLH) or Escherichia coli lipopolysaccharide (LPS) increased with parity. The NAb concentration binding KLH was greater for cows fed the glucogenic diet (9.63 +/- 0.08) compared with the lipogenic diet (9.26 +/- 0.08). In milk, cows fed the glucogenic diet had smaller NAb concentrations binding KLH (3.98 +/- 0.18) and LPS (2.88 +/- 0.17) compared with cows fed the mixed diet (KLH: 4.93 +/- 0.18; LPS: 3.70 +/- 0.17). The NAb concentration in plasma had a positive relation with energy balance variables: EB, dry matter intake, milk yield, and plasma cholesterol, whereas NAb concentration in milk had a negative relation with energy balance variables: EB, dry matter intake, and plasma cholesterol. Additionally, NAb concentrations in milk had a positive relation with plasma nonesterified fatty acid concentration and milk fat and protein percentage. There was a tendency for a positive relation of NAb concentration binding LPS in plasma and somatic cell count in milk. No significant relations were detected between NAb concentrations in milk or plasma and plasma beta-hydroxybutyrate concentration and liver triacyl glyceride content. In conclusion, NAb are present in both milk and plasma of dairy cows peripartum and NAb concentrations increase with parity. Furthermore, our data indicate that a negative energy balance in dairy cows in early lactation can be associated with compromised innate immune function as indicated by decreased NAb concentration in plasma.
 ...
PMID:Natural antibodies related to energy balance in early lactation dairy cows. 1802 40

The pathophysiology of preeclampsia (PET) implicates an inflammatory dysfunction. This study profiled this host response by challenging whole blood with lipopolysaccharide. Multiplex immunoassays determined interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70), IL-13, IL-17, granulocyte/granulocyte macrophage-colony stimulating factors (G-CSF/GM-SCF), interferon(IFN)-gamma, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein-1beta and tumor necrosis factor (TNF)-alpha levels. Secretory capacity was expressed in pg/million white cells or monocytes (+/-SEM). PET featured significantly higher IL-1beta, IL-2, IL-10, IL-13, G-CSF, IFN-gamma, MCP-1 and TNF-alpha monocyte secretory capacities (p < 0.05). The PET group exhibited an inflammatory hyper-responsiveness (p < 0.01) which was poorly described by the traditional Th1:Th2 dichotomy.
 ...
PMID:Host inflammatory response profiling in preeclampsia using an in vitro whole blood stimulation model. 1829

Increased levels of differentially regulated trout protein 1 (DRTP1) mRNA transcripts have been reported in fish after activation of the acute phase response. While the function of the DRTP1 protein still remains to be elucidated, this study focused on the genomic organisation of the gene, the quantification of the DRTP1 transcript in various tissues, and the isolation and analysis of the 5' regulatory region of the DRTP1 gene in rainbow trout (Oncorhynchus mykiss). Analysis of the DRTP1 genomic and cDNA sequences showed the gene to consist of four exons separated by three introns. Tissue localisation of the DRTP1 gene was performed by Northern analysis and validated by quantitative real-time PCR (qPCR). Six tissues (liver, intestine, spleen, brain, pituitary, and hypothalamus) were analysed. The tissues with the most abundant transcripts were the liver and the pituitary, with lesser amounts detected in the intestine, hypothalamus, brain and spleen. Genome walking allowed the isolation of a 934 bp sequence of the 5' regulatory region of the gene which was cloned, sequenced and in which potential transcription factor binding sites were identified. Promoter fragments of decreasing size were generated and transiently transfected into the human hepatoma cell line (HepG2). Inducibility of the promoter was determined by stimulation of the HepG2 cells containing the constructs with dexamethasone, polyinosinic:polycytidylic acid (poly I:C) and lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNFalpha). One construct, containing two potential C-EBP/beta sites and two NF-kappaB sites, exhibited the highest promoter induction (6.34 fold +/- SEM 0.5) when stimulated with human TNFalpha. A slightly shorter fragment containing one C-EBP/beta site and one NF-kappaB site did not show any significant inducibility when treated with TNFalpha. The loss of the C-EBP/beta and NF-kappaB in the shorter construct suggests that these sites, either individually or in combination, are critical for the induction of the DRTP1 promoter by TNFalpha.
 ...
PMID:Characterisation of the differentially regulated trout protein 1 (DRTP1) gene in rainbow trout (Oncorhynchus mykiss). 1899 23

Glutamine may have benefits during neonatal sepsis, but its effects on systemic inflammation are unknown. Our aim was to determine whether glutamine affects inflammation in neonatal endotoxemia. Eleven-day rat pups were given intraperitoneal injections of saline (control; C), endotoxin (300 microg/g Escherichia coli lipopolysaccharide) (E), saline with glutamine (2 mmol/g; G), or endotoxin with glutamine (EG). Animals were killed after 2 or 6 hours. Plasma glutamine (mmol/L) was measured enzymatically, and both tumor necrosis factor alpha (pg/mL) and interleukin 10 (IL-10) were measured by enzyme-linked immunosorbent assay. Results, expressed as mean +/- SEM, were analyzed by analysis of variance. Endotoxemia caused a rapid significant decrease in plasma glutamine at 2 hours (C, 0.73 +/- 0.06; E, 0.32 +/- 0.07; mean difference, 0.41 [95% confidence interval {CI, 0.17-0.64}]; P < .001), which was prevented by intraperitoneal glutamine (EG, 0.59 +/- 0.04; mean difference vs E, 0.27 mmol/L [95% CI, 0.03-0.50]; P < .05), indicating glutamine absorption, whereas CG animals had a plasma glutamine of 0.82 +/- 0.07. Tumor necrosis factor alpha was greatly increased by 2-hour endotoxemia (C, 27 +/- 7; E, 2247 +/- 43; mean difference, 2220 pg/mL [95% CI, 2012-2429]; P < .001), and this increase was partly prevented by glutamine (EG, 1991 +/- 91; P < .05 vs E; mean difference, 256; 95% CI, 47-465; P < .05). The effect of glutamine was more pronounced at 6 hours (C, 32 +/- 27; E, 799 +/- 193; EG, 219 +/- 75, C vs E mean difference, 767; 95% CI, 346-1188; P < .001; E vs EG mean difference, 580; 95% CI, 159-1001; P < .01). The IL-10 levels were also greatly increased by 2-hour endotoxemia (C = 55 +/- 21, E = 2429 +/- 58, EG = 1989 +/- 177; C vs E mean difference, 2374; 95% CI, 2740-2008; P < .001; E vs EG mean difference, 440; 95% CI, 74-807; P < .05). Glutamine administration partially prevents the sepsis-induced fall in plasma glutamine levels and reduces the concentration of both proinflammatory and antiinflammatory cytokines.
 ...
PMID:Glutamine decreases inflammation in infant rat endotoxemia. 1930 52

Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo. PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D). In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men. A total of 10 COPD, 10 T2D patients, and 10 healthy volunteers matched for age and BMI were recruited. Blood from each participant was exposed to 1 microg/L lipopolysaccharide (LPS) over 16 h with or without preincubation with 10 micromol/L of flavone, fisetin, morin, or tricetin. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant. Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P < 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P < or = 0.001]. Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin. The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.
 ...
PMID:Poly (ADP-ribose) polymerase-1-inhibiting flavonoids attenuate cytokine release in blood from male patients with chronic obstructive pulmonary disease or type 2 diabetes. 1932 92


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