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 products of proinflammatory genes such as interleukin-1beta (IL-1beta) and cyclooxygenase-2 (COX-2) initiate many of the events associated with sepsis. Transcription of these genes is subsequently down-regulated, whereas expression of anti-inflammatory genes such as secretory interleukin-1 receptor antagonist (sIL-1 RA) is maintained. Differential expression is associated with endotoxin tolerance, a cellular phenomenon common to sepsis and characterized by reduced proinflammatory gene expression after repeated exposure to lipopolysaccharide. As a model for endotoxin tolerance, we examined the expression of COX-2 and sIL-1 RA in a human promonocyte cell line, THP-1. We observed a 5-fold decrease in COX-2 protein in endotoxin-tolerant cells relative to control cells. In contrast, sIL-1 RA protein increased 5-fold in control and tolerant cells and remained elevated. Decreased COX-2 production is due to repressed transcription and not enhanced mRNA degradation. In addition, COX-2 protein is turned over rapidly. Transcription of sIL-1 RA is also repressed during tolerance. However, sIL-1 RA mRNA is degraded more slowly than COX-2 mRNA, allowing continued synthesis of sIL-1 RA protein that is very stable. These results indicate that differential expression during endotoxin tolerance occurs by transcriptional repression of COX-2 and by protein and mRNA stabilization of sIL-1 RA.
 ...
PMID:mRNA and protein stability regulate the differential expression of pro- and anti-inflammatory genes in endotoxin-tolerant THP-1 cells. 1076 54

Treatment of patients with sepsis with monoclonal antibodies against lipopolysaccharide, tumour necrosis factor or treatment with soluble TNF-receptors or interleukin-1 receptor antagonist have not had any effect on mortality. Treatment with intravenous polyclonal nonspecific immunoglobulin has been shown to have beneficial efficacy on mortality. However, the number of patients included in the latter treatment studies are limited, the patients studied are heterogeneous and do not allow to conclude that sepsis patients should be routinely treated with immunoglobulins.
 ...
PMID:[Non-antibiotic treatment of sepsis]. 1086 Apr 25

End-stage renal disease (ESRD) patients are known to suffer from chronic inflammation as the result of an ongoing subacute cytokine induction, which may contribute considerably to dialysis-related, long-term morbidity and mortality. Preparation of infusate from cytokine-inducing dialysis fluid and its administration in large quantities as well as the use of high-flux membranes bear the risk of aggravating the chronic inflammatory response among online hemodiafiltration (online HDF) patients. In order to assess the inflammatory risk associated with online HDF, we compared the cytokine induction profile of ESRD patients receiving either online HDF or low-flux hemodialysis (low-flux HD). Specifically, we measured spontaneous and lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNFalpha) and interleukin-1 receptor antagonist (IL-1Ra) release during ex vivo incubation of whole blood. Ultrapure dialysis fluid and polysulfone membranes were used for both treatment modalities. LPS-stimulated release of TNFalpha and IL-1Ra was elevated for both online HDF and low-flux HD patients compared to healthy individuals (TNFalpha: 2,336 +/- 346 and 2,192 +/- 398 versus 1,218 +/- 224 pg/106 white blood cells [WBC]; IL-1Ra: 2,410 +/- 284 and 2,326 +/- 186 versus 1,678 +/- 219 pg/106 WBC). Likewise, spontaneous production of TNFalpha, but not IL-1Ra, was higher in online HDF and low-flux HD patients than in normal controls (37 +/- 32 and 22 +/- 19 versus 0.8 +/- 0.3 pg TNFalpha/106 WBC). There was no difference in spontaneous and LPS-stimulated cytokine release between both dialysis groups. In addition, intradialytic cytokine induction was not significant for either treatment modality as spontaneous and LPS-stimulated cytokine release were not increased postdialysis. These findings indicate that online HDF does not contribute to chronic leukocyte activation and, consequently, does not place ESRD patients at greater risk with respect to inflammatory morbidity and mortality.
 ...
PMID:Cytokine induction in patients undergoing regular online hemodiafiltration treatment. 1091 61

The production and action of primary proinflammatory cytokines are strictly controlled by a series of circuits to avoid damage that they can cause if produced in excess. Interleukin-10 and interleukin-1 receptor antagonist contribute to the control of the magnitude of the inflammatory responses in vivo. Benzydamine, a non-steroidal anti-inflammatory drug that has been shown to have suppressive activity for the proinflammatory cytokines, tumor necrosis factor-alpha and interleukin-1beta, was investigated for its effects on interleukin-10 and interleukin-1ra production. The drug did not modify the production of interleukin-10 and interleukin-1ra by peripheral blood mononuclear cells stimulated with lipopolysaccharide, under conditions where tumor necrosis factor-alpha and interleukin-1beta were decreased. The antiinflammatory capacity of benzydamine might thus result from its ability to reduce the production of proinflammatory cytokines, without affecting antiinflammatory factors.
 ...
PMID:Differential effect of benzydamine on pro- versus anti-inflammatory cytokine production: lack of inhibition of interleukin-10 and interleukin-1 receptor antagonist. 1098 27

Interleukin-1beta acts on the CNS to induce fever, neuroendocrine activation and behavioural depression. We have previously demonstrated that interleukin-1beta is synthesized in glial cells and macrophages of circumventricular organs and choroid plexus after intraperitoneal administration of bacterial lipopolysaccharide. Whether, and how, interleukin-1beta produced in glial cells affects neuronal functioning is unknown. Diffusion throughout the extracellular space is an important pathway by which factors produced by glial cells act on distant cells, a phenomenon coined "volume transmission". The present study assessed diffusion of recombinant rat interleukin-1beta, recombinant human interleukin-1 receptor antagonist and 10mol. wt dexran in the rat CNS after intracerebroventricular administration to model interleukin-1beta release from choroid plexus. Immunocytochemistry with specific antibodies directed against interleukin-1beta and interleukin-1 receptor antagonist revealed that these molecules rapidly penetrated into periventricular tissue and spread along white matter fibre bundles and blood vessels in the caudoputamen, hypothalamus and amygdala. The transcription factor nuclear factor kappa B and the immediate-early gene product Fos were detected immunocytochemically to reveal interleukin-1beta action. Intracerebroventricular infusion of interleukin-1beta induced nuclear factor kappa B translocation in choroid plexus, ependymal cells, basolateral amygdala, cerebral vasculature and meninges. Fos immunoreactivity was found in the supraoptic and paraventricular hypothalamus and central amygdala. We propose that intracerebroventricular injected interleukin-1beta can enter the brain parenchyma and act as a "volume transmission" signal in, for example, the basolateral amygdala where it might activate a neuronal projection to the central amygdala.
 ...
PMID:Diffusion and action of intracerebroventricularly injected interleukin-1 in the CNS. 1111 45

Although the natural interleukin-1 receptor antagonist (IL-1Ra) has been shown to be produced by microglial cells in response to immune stimuli, nothing was known about the ability of these cells in primary culture to produce the different isoforms of IL-1Ra. Using RT-PCR, we first confirmed that mixed glial cell cultures from newborn rats respond to the cytokine inducer, lipopolysaccharide, by synthesizing IL-1Ra mRNA. Using double immunostaining, we showed that IL-1Ra was detected in microglia but not in astrocytes. Using Western blotting, we finally demonstrated that the IL-1Ra1 isoform was secreted in the supernatant of mixed glial cell cultures, and its production increased in response to lipopolysaccharide. The three different IL-1Ra isoforms were constitutively expressed in cell lysates and their levels increased after lipopolysaccharide treatment, except for IL-1Ra3. These results point to the ability of microglial cells in primary culture to produce the different isoforms of IL-1Ra.
 ...
PMID:Production of interleukin-1 receptor antagonist isoforms by microglia in mixed rat glial cells stimulated by lipopolysaccharide. 1112 14

Microbial components such as bacterial endotoxin lipopolysaccharide (LPS) can trigger highly lethal septic shock. The cardinal features of septic leukocytes include the repressed production of inflammatory cytokines, such as interleukin-1 beta (IL-1beta), and elevated production of anti-inflammatory cytokines, such as secretory interleukin-1 receptor antagonist (sIL-1RA). Pro- and anti-inflammatory cytokine gene transcriptions are equally repressed in septic leukocytes due to disruption of the LPS signaling pathway at the level of interleukin-1 receptor-associated kinase. The selective elevation of sIL-1RA protein in septic blood is caused by efficient translation of residual sIL-1RA message. In this study, we report that the LPS-inducible phosphatidylinositol 3-kinase (PI3-kinase)-dependent signaling pathway contributes to the elevated translation of sIL-1RA in septic/LPS-adapted leukocytes. We also observe that this pathway is gene specific and does not affect the production of proinflammatory IL-1beta protein.
 ...
PMID:The phosphatidylinositol 3-kinase pathway selectively controls sIL-1RA not interleukin-1beta production in the septic leukocytes. 1127 36

The endogenous interleukin-1 receptor antagonist is the natural inhibitor of the biological effects of interleukin-1 during inflammation. Interleukin-1 receptor antagonist refers to three isoforms: one secreted and two intracellular forms (types I and II). The objective of the present study was to investigate the expression of interleukin-1 receptor antagonist isoforms in the rat brain in vivo in response to an i.p. injection of lipopolysaccharide. The interleukin-1 receptor antagonist was studied at the messenger and protein levels by reverse transcription-polymerase chain reaction and western blot analysis, respectively. Interleukin-1 receptor antagonist messenger RNA was constitutively expressed in the brain and its expression increased in response to lipopolysaccharide. The three interleukin-1 receptor antagonist protein isoforms were up-regulated after lipopolysaccharide treatment in a time-dependent manner. Their relative expression differed according to the isoform and brain region studied. Double immunofluorescence staining revealed interleukin-1 receptor antagonist positive neurons and microglia in hippocampus 24h after lipopolysaccharide stimulation. These results demonstrate for the first time that brain cells are able to produce interleukin-1 receptor antagonist isoforms in response to a peripheral immune challenge with a predominance of the secreted over intracellular forms.
 ...
PMID:Characterization of interleukin-1 receptor antagonist isoform expression in the brain of lipopolysaccharide-treated rats. 1131 97

Estrogen's action on bone may be mediated by cytokines produced by monocytes. We have reported a decreased ratio of interleukin-1beta (IL-1beta) to interleukin-1 receptor antagonist (IL-1ra) produced by whole blood cultures in vivo in women taking hormone replacement therapy (HRT). Also, one study has shown an effect of estradiol on tumor necrosis factor-alpha (TNF-alpha) secretion by separated monocytes in vitro. The aim of this study was to evaluate the effect of estrogen in vitro on the secretion of cytokines using whole blood cultures. Subjects consisted of 12 healthy postmenopausal women, ages 57-69 years, 4-20 years since menopause. Cytokines IL-1beta, interleukin-1alpha (IL-1alpha), IL-1ra, interleukin-6 (IL-6), TNF-alpha, and granulocyte macrophage-colony stimulating factor (GM-CSF) were measured in unstimulated and in stimulated (500 ng/mL lipopolysaccharide [LPS]) whole blood cultures treated with 17beta-estradiol (E(2)) at concentrations of 10(-12)--10(-6) mol/L. We found significant decreases in the spontaneous secretion of IL-6, TNF-alpha, IL-1ra, IL-1beta, and ratio of IL-1beta/IL-1ra compared with control, at physiological concentrations of E(2). The action of E(2) was blocked by the use of the antiestrogen ICI 182780 in coculture. A decrease in cytokine secretion was not observed when the inactive form of estrogen, 17alpha-estradiol, was used in place of 17beta-estradiol. GM-CSF and IL-1alpha were not detectable in unstimulated cultures. Cytokine levels measured in stimulated cultures were not attenuated by treatment with E(2). We conclude that E(2) inhibits the spontaneous secretion of cytokines measured in whole blood cultures at physiological concentrations, and that the powerful stimulatory effect of LPS prevents any significant inhibition by E(2) in stimulated cultures.
 ...
PMID:The effect of 17beta-estradiol on production of cytokines in cultures of peripheral blood. 1147 88

The psoriatic inflammatory process is characterized by an overexpression of pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1beta compared with a relative deficiency of anti-inflammatory factors such as interleukin-10 and the interleukin-1 receptor antagonist (interleukin-1Ra). Gene polymorphisms that affect cytokine production may contribute to the disease-associated cytokine imbalance and influence susceptibility to psoriasis. Here, we investigated the relationship between polymorphisms in the genes encoding for tumor necrosis factor-alpha (G-238A, G-308A), interleukin-1beta (C-511T, T+3953C), and interleukin-1Ra (intron 2), and cytokine production in peripheral blood mononuclear cells of healthy donors, and analyzed the distribution of these polymorphisms in patients with psoriasis vulgaris (n = 231) and healthy controls (n = 345). Carriage of tumor necrosis factor A-238 allele 2 (-238*A) was associated with increased production of tumor necrosis factor-alpha in response to lipopolysaccharide in vitro, and with early onset disease (< 40 y), especially in male patients with psoriasis [32% vs 7% in male controls; odds ratio = 6.78, 95% confidence interval = (3.18-15.15), p(adjusted) = 2 x 10(-7)]. Carriage of the interleukin-1B-511*1 (-511*C) homozygous genotype was associated with increased production of interleukin-1Ra in response to lipopolysaccharide and interleukin-10, and with late onset psoriasis [> or = 40 y; 61% vs 44% in controls; odds ratio = 2.04, 95% confidence interval = (1.19-3.53), p(adjusted) = 0.0419]. These findings indicate that gene polymorphisms associated with altered cytokine responses in vitro may modify age of onset of psoriasis. They also provide further evidence that patients with early and late onset psoriasis differ in their genetic background.
 ...
PMID:Promoter polymorphisms of the genes encoding tumor necrosis factor-alpha and interleukin-1beta are associated with different subtypes of psoriasis characterized by early and late disease onset. 1185 89


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