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)

Several studies have demonstrated that diabetes is a risk factor for developing periodontal disease, increasing its prevalence and severity. Furthermore, periodontitis may impair the metabolic control and adequate treatment of diabetic patients. LPS from Gram-negative bacteria penetrates the periodontal tissues and subsequently recruits and activates immune cells. Progression to severe periodontitis with loss of supporting structures is mediated by several factors, including secretion of a broad spectrum of inflammatory and destructive (PGE2). mediators such as cytokines (TNF-alpha, IL-1b and IL-6), chemokines (IL-8) and prostaglandin E2. The aim of this work is to investigate differences in the TNF-a, IL-1b and IL-6 expression and prostaglandin E2 (PGE2) release in blood from diabetic patients with and without aggressive periodontitis (AP) stimulated with lipopolysaccharide (LPS). For this purpose we recruited 29 Type 1 diabetes mellitus (DM) patients, 14 with AP and 15 without AP. Fourteen healthy individuals formed the control group. For cytokine expression and PGE2 secretion, an ex vivo whole blood culture system was used. Cytokines and PGE2 were detected by commercial immunometric assays. A wide range of inter-individual variability in spontaneous and LPS-induced TNF-alpha, IL-1b and IL-6 levels in patient groups and controls was found. The mean of spontaneous and LPS-induced TNF-alpha and IL-1b levels did not differ significantly (p > 0.5) when patients were compared to control individuals. Although not significant, the spontaneous TNF-alpha, IL-1b and IL-6 levels in the group of Type 1 DM with AP were higher than in controls, while in diabetic patients without AP, these values were depressed in comparison with controls. In both groups of patients, the means of LPS-induced IL-6 levels were higher than the controls but the differences observed were not significant (p = 0.07). However, the LPS-induced PGE2 levels varied significantly when all groups were compared (p = 0.007). The means of LPS-induced PGE2 levels for Type 1 diabetic patients with AP (p = 0.0009) and without AP (p = 0.024) were significantly higher than the levels observed for healthy controls. Finally, we conclude that Type 1 diabetic patients with or without AP did not express higher LPS-induced TNF-a, IL-1b and IL-6 levels than controls. However, the PGE2 levels released were significantly higher than those detected in controls.
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PMID:Ex vivo lipopolysaccharide (LPS)-induced TNF-alpha, IL-1beta, IL-6 and PGE2 secretion in whole blood from Type 1 diabetes mellitus patients with or without aggressive periodontitis. 1465 85

Cytokines are important mediators of inflammatory and proliferative responses in disease states including atherosclerosis. Genetic variations in cytokine production could potentially influence the outcome of these responses. The aim of this study was to determine whether cytokine gene polymorphism might influence the development of atherosclerotic renal artery stenosis. Sixty-six patients with atherosclerotic renal artery stenosis and 100 normal healthy individuals were genotyped for interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-2 promoter region polymorphism. TNF-a, TNF-d, and IL-10 microsatellite polymorphisms were also analyzed. The frequency of the anti-inflammatory cytokine IL-10 promoter (-1082 A positive) GA and AA genotypes which are associated with low production were higher in the patient group when compared to the control group. The AA-TT-AA homozygous genotype combination of three single-nucleotide polymorphisms at -1082, -819, and -592 in the IL-10 gene was also observed at a higher frequency in the patient group compared to the controls. The frequency of TNF-alpha, IL-6, and IL-2 polymorphisms did not show any significant difference between the patient and control groups. To correlate IL-10 genotypes with differences in IL-10 protein expression, in vitro mRNA and protein levels were analyzed in lipopolysaccharide-stimulated peripheral blood mononuclear cells from 22 patients with renal artery stenosis and 33 controls. Individuals genotyped as A positive at position -1082 produced lower levels of IL-10 protein and had lower copy numbers of mRNA when compared to individuals genotyped as A negative in both patient and control groups. The increased frequency of the low producer IL-10 promoter, -1082 A-positive genotype in patients with renal artery stenosis, suggests that IL-10 may protect against the development of atherosclerotic renovascular disease.
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PMID:Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10. 1510 79

Proinflammatory cytokines produced by monocytes, like Interleukin-6 (IL-6), Interleukin-8 (IL-8), and tumor necrosis factor (TNF-alpha) are known for their pivotal role in the initiation of the inflammatory response following cardiopulmonary bypass (CPB). Catecholamines like epinephrine (Epi) and norepinephrine (Nor) are often necessary to stabilize the cardiac function in the early postoperative period and may influence the cytokine expression in monocytes. In this study we investigated the effects of Epi and Nor on IL-6, IL-8 and TNF-alpha expression in human monocytes stimulated with lipopolysaccharide (LPS) in whole blood, analyzed intracellularly by flow cytometry. Kinetics of intracellular proinflammatory cytokine production and LPS ED(50) were obtained. To simulate different stages of inflammation in vivo, varying concentrations of LPS (0.2 ng/ml, 1 ng/ml and 10 ng/ml) were used for stimulation. After a stimulation with LPS TNF-alpha was the first produced cytokine, followed by IL-8 and IL-6. All cytokines peaked from 3 h to 6 h. Epi and Nor had comparable effects on the expression of IL-6, IL-8 and TNF-a in monocytes. Both inhibited IL-6 and TNF-alpha expression in a concentration dependent manner whereas IL-8 expression remained unchanged. We conclude that monocytes are targets for Epi and Nor concerning their cytokine expression. The inhibiting effects of Nor and Epi were almost identical for all cytokines. Cytokine expression was affected most at low LPS concentrations.
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PMID:Effect of catecholamines on intracellular cytokine synthesis in human monocytes. 1521 48

It has been shown that some antibiotics can modify cytokine production. We have examined the effect of rifampicin on secretion of interleukin-1beta (IL-1beta), IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated or heat killed staphylococci (Pansorbin) stimulated monocytes. Secretion of IL-1beta and TNF-a were significantly inhibited (P<0.002) whereas secretion of IL-6 and IL-10 were significantly increased (P<0.003) by rifampicin treated mononuclear cells. Rifampicin had immunomodulatory effects through its capacity to alter the secretion of tested cytokines by human monocytes.
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PMID:Immunomodulating activity of rifampicin. 1533 11

The authors investigated the effects of lipopolysaccharide (LPS) on the blood-brain barrier (BBB) integrity and the activity of astrocytes during the Nw-nitro-L-arginine methyl ester (L-NAME) hypertension followed by angiotensin (ANG) II in rats. They measured the changes in the BBB permeability using the Evans blue (EB) dye and concomitantly in the levels of TNF-a, IL-1b, and IL-6 in serum and nitric oxide in plasma. The authors performed two tight junction-specific proteins, zonula occludens-1 and occludin, and glial fibrillary acidic protein, by using immunohisto-chemical method. The serum levels of TNF-a, IL-1 IL-6, and the plasma level of nitric oxide significantly increased in LPS-treated rats (p<.01). The EB dye extravasation increased in cerebellum (p<.001) and diencephalon (p<.05) of L-NAME plus ANG II-treated animals. However, LPS reduced the increased EB dye extravasation in the brain regions of L-NAME-induced hypertensive rats treated with ANG II (p<.001). In L-NAME, there was a considerable loss of staining in both zonula occludens-1 and occludin. Staining for zonula occludens-1 and occludin was highly intensive in animals treated with LPS. Glial fibrillary acidic protein staining was seen in a few astrocytes in brains of L-NAME-treated animals. However, this staining showed an increased intensity in the brain sections of animals treated with LPS. This study indicates that, in L-NAME hypertensive rats, ANG II leads to an increase in the extravasation of EB dye to brain as a result of decreased activity of tight junction proteins and astrocytes, and LPS could significantly attenuate the EB dye transport to the brain through the increased activity of tight junction proteins and astrocytes.
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PMID:Effects of lipopolysaccharide on the blood-brain barrier permeability in prolonged nitric oxide blockade-induced hypertensive rats. 1576 98

1. Acute lung injury (ALI) or acute respiratory distress syndrome is a serious clinical problem with high mortality. N-Acetylcysteine (NAC) is an anti-oxidant and a free radical scavenger. It has been reported recently that NAC ameliorates organ damage induced by endotoxin (lipopolysaccharide; LPS) in conscious rats. The present study was designed to evaluate the effects of NAC on LPS-induced ALI and other changes in anaesthetized rats. 2. Sprague-Dawley rats were anaesthetized with pentobarbital (40 mg/kg, i.p.). Endotracheal intubation was performed to provide artificial ventilation. Arterial pressure and heart rate were monitored. The extent of ALI was evaluated with the lung weight (LW)/bodyweight ratio, LW gain, exhaled nitric oxide (NO) and protein concentration in bronchoalveolar lavage (PCBAL). Haematocrit, white blood cells, plasma nitrate/nitrite, methyl guanidine (MG), tumour necrosis factor (TNF)-alpha and interleukin (IL)-1b were measured. Pathological changes in the lung were examined and evaluated. 3. Endotoxaemia was produced by injection of 10 mg/kg, i.v., LPS (Escherichia coli). Animals were randomly divided into three groups. In the vehicle group, rats received an i.v. drip of physiological saline solution (PSS) at a rate of 0.3 mL/h. The LPS group received an i.v. drip of PSS for 1 h, followed by LPS (10 mg/kg by slow blous injection, i.v., over 1-2 min). Rats in the LPS + NAC group received NAC by i.v. drip at a rate of 150 mg/kg per h (0.3 mL/h) for 60 min starting 10 min before LPS administration (10 mg/kg by slow blous injection, i.v., over 1-2 min). Each group was observed for a period of 6 h. 4. N-Acetylcysteine treatment improved the LPS-induced hypotension and leukocytopenia. It also reduced the extent of ALI, as evidenced by reductions in LW changes, exhaled NO, PCBAL and lung pathology. In addition, NAC diminished the LPS-induced increases in nitrate/nitrite, MG, TNF-a and IL-1b. 5. In another series of experiments, LPS increased the mortality rate compared with the vehicle group (i.v. drip of PSS at a rate of 0.3 mL/h) during a 6 h observation period. N-Acetylcysteine, given 10 min prior to LPS, significantly increased the survival rate. 6. The results of the present study suggest that NAC exerts a protective effect on the LPS-induced ALI. The mechanisms of action may be mediated through the reduction of the production of NO, free radicals and pro-inflammatory cytokines.
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PMID:N-acetylcysteine abrogates acute lung injury induced by endotoxin. 1644 96

The impact of fish oil on tumour necrosis-alpha (TNF-alpha) production by macrophages stimulated by lipopolysaccharide (LPS) was examined in mice. Animals were fed high fat diets (20% fat wt/wt) rich in fish oil, corn oil or coconut oil for 4 weeks; a group of mice fed a low fat diet (5%) was included. Peritoneal macrophages were incubated with or without LPS for 24 h and the level of TNF-alpha measured in the culture medium. TNF-alpha mRNA was measured every 30 min for 2 h after addition of LPS by dot blot hybridization. Post-transcriptional studies were performed using actinomycin D and/or cycloheximide in the fish oil and corn oil groups. Production of TNF-a by macrophages was increased by more than 10-fold in the fish oil group compared to other groups; no difference was seen between low fat, corn oil and coconut oil groups. Compared to the low fat diet, higher levels of TNF-alpha mRNA were detected in the fish oil group (2.3-fold), and to a lesser extent in the coconut oil and corn oil groups (1.5- 1.2 fold, respectively). TNF-alpha mRNA accumulation in the fish oil group was not due to increased stability of mRNA and protein synthesis was not involved in this phenomenon. The authors discussed the mechanisms by which fish oil could increase TNF-alpha production by LPS stimulated macrophages.
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PMID:Fish oil enhances macrophage tumour necrosis factor-alpha mRNA expression at the transcriptional level. 1684 94

Intracellular signaling pathways regulated by Toll-like receptor 4 (TLR4) and tumor necrosis factor-alpha (TNF-alpha) both activate NFkappaB. This suggests that lipopolysaccharide (LPS) and TNF-alpha should alter transcription of a common set of genes. We tested this hypothesis by treating first passage human umbilical endothelial cells (HUVEC) for 6 h with LPS (50 ng/ml+1 microg/ml CD14) or TNF-alpha (10 ng/ml) and analyzing changes in gene expression by microarray analysis (Affymetrix GeneChips). LPS and TNF-alpha increased expression of 191 common genes and decreased expression of 102 genes. Regulated transcripts encoded for a large number of chemokines, adhesion molecules, procoagulant factors, and molecules that affect cell integrity. Based on the microarray analysis and subsequent confirmation of specific genes by Northern analysis, all 203 genes altered by LPS were altered by TNF-alpha. An additional 17 genes were induced only by TNF-alpha and the expression of 46 was reduced. There were, however, some differences in the kinetics of changes. We also showed that endogenous CD14 was present on these early passage cells and exogenous CD14 was not necessary for most of the LPS response. An autocrine effect from LPS induced expression of TNF-alpha also was ruled out by blocking TNF-alpha with monoclonal antibodies. In conclusion, LPS induces a robust alteration in gene expression in HUVEC that is very similar to that induced by TNF-a. This LPS effect on endothelium could play an important role in the innate immune response.
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PMID:Lipopolysaccharide and TNF-alpha produce very similar changes in gene expression in human endothelial cells. 1692 Dec 52

The present study was designed to investigate whether administration of CoPPIX, an HO-1 inducer, could significantly inhibit TNF-alpha and Hmgb1 expression and thus attenuate the acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Acute lung injury was induced successfully by intratracheal administration of LPS (0.5 mg/kg) in male BALB/c mice. CoPPIX or ZnPPIX (an HO-1 inhibitor) was administered to mice 24 h prior to LPS exposure. It was found that CoPPIX (5, 10 mg/kg, i.p.) caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and EBA leakage at 24 h after LPS challenge. Furthermore, the histopathologic findings indicated that alveolitis with leukocyte infiltration in the alveolar space was less severe in the CoPPIX-treated mice than in the mice treated with LPS alone. In addition, CoPPIX was also believed to have down-regulated the expression of LPS-induced proinflammatory cytokines, including early proinflammatory cytokine TNF-a, and late proinflammatory cytokine Hmgb1. In contrast, no obvious difference was observed between the ZnPPIX group and the LPS group. These findings demonstrate the significant protection of CoPPIX against LPS-induced ALI, and the effect mechanism of CoPPIX was associated with decreasing the expression of TNF-a and Hmgb1.
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PMID:Heme oxygenase-1 upregulation significantly inhibits TNF-alpha and Hmgb1 releasing and attenuates lipopolysaccharide-induced acute lung injury in mice. 1844 82

Activation of the innate immune system by pathogen-associated molecular patterns (PAMPs) may direct specific immune responses and as a consequence probably significantly affect vaccination. Previously, we described modulation of specific antibody responses to systemically administered model antigens by intravenously (i.v.) as well as intratracheally (i.t.) administered PAMP such as the endotoxin lipopolysaccharide (LPS). In this study effects of various doses of i.t.-administered LPS on primary and secondary specific total and individual isotype (IgM, IgG and IgA)-specific antibody responses of chickens simultaneously i.t. challenged with various doses of human serum albumin (HuSA) were determined. i.t.-administered LPS enhanced primary and secondary HuSA-specific total and isotype-specific antibody titers depending on the dose of LPS and the dose of simultaneously administered HuSA. i.t.-administered HuSA enhanced primary and secondary total antibody responses to 'environmental' LPS as shown in birds receiving the zero i.t. LPS treatment, which also depended on dose of HuSA. HuSA administration decreased antibody responses to high doses of LPS. Body weight gain as a measurement of an acute phase cachectin response to LPS was affected by a HuSA by LPS interaction, indicating that simultaneously administered higher doses of HuSA decreased LPS-induced cachectin responses of the birds. Our results suggest a complex interaction of innate and specific immune system activating airborne antigens, which may have significant consequences for vaccination and husbandry management procedures.
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PMID:Effect of concurrent intratracheal lipopolysaccharide and human serum albumin challenge on primary and secondary antibody responses in poultry. 1869 97


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