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)

1. The actions of the following pyrogens: lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (Poly-I:C), human interleukin (IL)-1 alpha and IL-1 beta, human IL-6 and rat interferon (INF) on corticotrophin-releasing factor-41 (CRF-41) and prostaglandin E2 (PGE2) release from the intact rat hypothalamus in vitro have been studied. 2. Rat hypothalami were incubated in vitro in an artificial cerebrospinal fluid. Immunoreactive (ir)-CFR-41 and PGE2 released into the medium were measured by two-site enzyme amplified immunometric assay (EAIA) and radioimmunoassay (RIA) respectively. 3. Human IL-6 (1 to 10,000 IU ml-1) caused a dose-dependent release of irCRF-41, rising to a maximal 3-4 fold increase over basal at the highest dose tested. Human IL-1 alpha (1 to 1000 IU ml-1), human IL-1 beta (1 to 1000 IU ml-1), poly-I:C (10 pg ml-1 to 100 micrograms ml-1) and rat INF (1 to 10,000 IRu ml-1) all failed to alter irCRF-41 release. 4. LPS (1 mg ml-1) caused a 35% decrease in irCRF-41 release; however, over the dose-range of 0.1 microgram ml-1 to 100 micrograms ml-1, LPS failed to alter irCRF-41 release. The decreased irCRF-41 release in response to LPS (1 mg ml-1) was accompanied by a decrease in the subsequent 56 mM KCl stimulation of irCRF-41. 5. Human IL-1 alpha and IL-1 beta (1000 IU ml-1) were able to stimulate the release of irPGE2 from intact hypothalami, causing a 2 fold increase over basal release. Poly-I:C (100 microg ml-1), LPS (0.1 microg ml-1 to 1 mg ml-1), rat INF (10,000 IRu ml-1) and human IL-6 (1 to 10,000 iu ml-1) all failed to alter irPGE2release.6. In conclusion, these results suggest that the in vitro release of CRF-41 and PGE2, in response to pyrogens, are mediated via different cytokines. In view of this it is possible that different cytokines may mediate the temperature, prostaglandin and hypothalamo-pituitary-adrenocortical axis activation seen during pyrogenic stimulation in vivo.
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PMID:Effects of pyrogenic immunomodulators on the release of corticotrophin-releasing factor-41 and prostaglandin E2 from the intact rat hypothalamus in vitro. 849 49

Expression of CD14 on peripheral blood monocytes and serum levels of the 53 kD soluble CD14 antigen were investigated in patients with end-stage renal failure who were undergoing chronic hemodialysis (HD) with either cuprophane/hemophane (CU/HE) low-flux (LF) or polysulfone/polyamide (PS/PA) high-flux (HF) membranes. Baseline expression of CD14 was significantly lower in HD patients compared to uremic patients and normal controls. Patients using PS/PA membranes disclosed a further decreased CD14 expression than patients with CU/HE membranes. Specific fluorescence intensity for CD14 increased 15 minutes after the start of the dialysis session and was on average 22% higher after hemodialysis. The serum levels of sCD14 were elevated about 2.5-fold in HD patients compared to healthy controls (5.4 +/- 1.3 vs. 2.2 +/- 0.5 mg/liter, P < 0.0001) and were significantly higher compared to non-dialyzed patients with chronic renal failure (3.9 +/- 1.0 mg/liter, P < 0.001). After regular dialysis with high-flux membranes, soluble CD14 serum concentrations significantly increased (P < 0.001) compared to pre-dialysis levels. Values of soluble CD8 (54 kD) were elevated only 1.5-fold in HD patients relative to healthy controls, whereas serum levels of the low molecular weight soluble CD23 (20 kD) 12 and 19-fold in patients treated with HF-HD and LF-HD, reflecting the renal impairment and filtration through HF membranes. Thus, high sCD14 values in HD patients may stem from increased release of the up-regulated membrane antigen due to monocyte activation during hemodialysis treatment. Since the CD14 antigen is involved in LPS-induced monocyte activation, the influence of lipopolysaccharide on CD14 expression and sCD14 release was investigated in vitro. Addition of 1 ng/ml or 0.01 ng/ml LPS to whole blood significantly enhanced monocyte CD14 expression after 30 or 60 minutes of incubation. The release of soluble CD14 by cultured peripheral blood monocytes significantly increased in the presence of 0.01 ng/ml LPS during a five-day incubation experiment. Our results demonstrate an enhanced expression of CD14 by monocytes after HD and increased sCD14 serum levels possibly due to chronic exposure to trace amounts of endotoxins, as supported by in vitro experiments.
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PMID:Monocyte cell-surface CD14 expression and soluble CD14 antigen in hemodialysis: evidence for chronic exposure to LPS. 854 3

We investigated the chemical and anatomical features of nitric oxide synthase (NOS)-containing neurons in the paraventricular and supraoptic nuclei in the rat hypothalamus using combinations of enzyme histochemistry, in situ hybridization and immuno-histochemistry. Neurons expressing NOS mRNA completely overlapped with NADPH-diaphorase-positive neurons. Topographical distribution of NOS was segregated from that of CRF-containing parvicellular neurons in the posterior paraventricular nucleus but overlapped with that of magnocellular neurons. In the paraventricular nucleus, 70% of oxytocin neurons contained NOS, which corresponded to one half of NOS neurons. About one third of vasopressin-immunoreactive neurons were NADPH-diaphorase-positive and the same proportion of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. In the supraoptic nucleus, 50% of oxytocin neurons were NADPH-diaphorase-positive, which corresponded to 40% of NOS neurons. About 25% of vasopressin neurons were NADPH-diaphorase-positive, and 30% of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. When NADPH-diaphorase histochemistry was performed first, subsequent immunostaining was markedly perturbed. Using fluoro-gold as a retrograde tracer, 4% of NADPH-diaphorase-positive neurons were shown to contribute to the descending projection to the spinal cord. About 40%-50% of NADPH-diaphorase-positive neurons exhibited Fos immunoreactivity after injection of lipopolysaccharide or hypertonic saline, while only 10%-15% of these neurons expressed Fos in response to immobilization or pain. Endogenous NO may be involved in the regulation of magnocellular functions, especially when the internal environment is disturbed.
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PMID:Nitric oxide synthase-containing magnocellular neurons of the rat hypothalamus synthesize oxytocin and vasopressin and express Fos following stress stimuli. 895 94

Bacterial endotoxins produce profound activation of the hypothalamo-pituitary-adrenal axis, mediated by stimulation of hypothalamic CRF neurons. Although a number of studies have described direct pituitary actions of inflammatory mediators, the effects of inflammatory stimuli on the sensitivity of corticotropes to CRF remain to be elucidated. The aim of this study was to determine the effects of inflammatory stress on the CRF receptor 1 (CRF-R1) messenger RNA (mRNA) levels in the rat pituitary. The systemic injection of endotoxin [lipopolysaccharide (LPS); 50 microg/kg, i.v.] increased plasma concentrations of ACTH and corticosterone. Ribonuclease protection analysis of total RNA isolated from individual whole pituitaries indicated that LPS produced a significant decrease in CRF-R1 mRNA that was evident by 2 h after injection (to 57% of control) and more marked by 6 h (to 38% of control). To evaluate whether the decrease in CRF-R1 mRNA was dependent upon increased exposure to CRF and/or vasopressin (AVP), LPS was injected with an anti-CRF antiserum, a CRF receptor antagonist (Astressin), or anti-AVP antiserum. A strong inhibition of the ACTH response to LPS was produced by pretreatment with anti-CRF antiserum, Astressin, or anti-AVP antiserum. However, these treatments had no effect on the decrease in CRF-R1 mRNA produced by LPS, indicating that neither CRF nor AVP are obligatory mediators of this pituitary response. The hypothesis that LPS might have direct pituitary effects on CRF-R1 mRNA levels was tested in vitro. Indeed, decreases in CRF-R1 mRNA to 43% and 53% of the control level were observed in rat anterior pituitary cell cultures that were treated with either LPS itself or the inflammatory mediator interleukin-1beta, respectively. Collectively, these results show that CRF receptor mRNA levels in the pituitary of the rat are markedly reduced by systemic LPS treatment and that this decrease is not dependent upon increased exposure of the pituitary to CRF or AVP, but may involve direct effects within the pituitary of either LPS itself or ensuing cytokine production.
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PMID:Endotoxin decreases corticotropin-releasing factor receptor 1 messenger ribonucleic acid levels in the rat pituitary. 907 23

We investigated the cell content and production of IL-1beta and IL-1 receptor antagonist (Ra) by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) obtained from 15 undialyzed patients with chronic renal failure (CRF; estimated GFR <10 ml/min), 15 patients on chronic hemodialysis (HD) and 15 healthy controls. These cytokines were measured by ELISA. The cell content of IL-1beta in freshly obtained PBMC was not detectable in any group. In contrast, that of IL-1Ra in CRF (1,807 +/- 370 pg/ml, p < 0.05) as well as in HD (1,791 +/- 151 pg/ml, p < 0.001) was significantly higher than that of the controls (907 +/- 156 pg/ml). In unstimulated cultured PBMC, spontaneous production of IL-1beta in CRF (66 +/- 13 pg/ml, p < 0.05) and in HD (81 +/- 29 pg/ml, p < 0.05) was significantly higher than that of the controls (26 +/- 3 pg/ml). In contrast, comparison of spontaneous production of IL-1Ra in the three groups was not significantly different. In LPS-stimulated PBMC, IL-1beta production in CRF (10,896 +/- 1,359 pg/ml, p < 0.01)and in HD(11,441 +/- 1,400 pg/ml, p < 0.01) was significantly higher than that of the controls (6,117 +/- 572 pg/ml). However, IL-1Ra production by LPS-stimulated PBMC in the three groups was not significantly different. Moreover, the spontaneous IL-1Ra/IL-1beta production ratio in CRF (140 +/- 16, p < 0.01) and in HD (142 +/- 19, p < 0.01) was significantly lower than that of the controls (294 +/- 41). The present study demonstrates that cytokine production by PBMC in undialyzed CRF patients as well as in hemodialyzed patients is heightened and may induce impaired function of the immunological system before CRF patients are introduced to dialysis.
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PMID:Increased production of interleukin-1beta and interleukin-1 receptor antagonist by peripheral blood mononuclear cells in undialyzed chronic renal failure. 917 Dec 96

We investigated the effectiveness of lipopolysaccharide (LPS) and muramyl dipeptide (MDP) administered into the brain to induce anorexia in acutely fasted Wistar rats allowed to refeed. We also assayed for changes in mRNA levels of IL-1 system components, TNF-alpha, TGF-beta1, glycoprotein 130 (gp 130), leptin receptor (OB-R), pro-opiomelanocortin (POMC), neuropeptide Y (NPY), glucocorticoid receptor (GR), and CRF receptor (CRF-R) in selected brain regions. The data show that LPS and MDP induced anorexia differentially during refeeding. LPS-induced anorexia was of a stronger magnitude and duration than that of MDP. RNase protection assays showed that LPS and MDP significantly increased the expression of IL-1beta, IL-1 receptor type I, and TNF-alpha mRNAs in the cerebellum, hippocampus, and hypothalamus; LPS was more potent in all cases. MDP treatment, on the other hand, induced a stronger increase in hypothalamic levels of IL-1 receptor antagonist (IL-1Ra) and TGF-beta1 mRNAs relative to LPS. In addition, competitive RT-PCR analysis showed that LPS induced an eleven-fold increase in IL-1alpha mRNA in the hypothalamus relative to vehicle. These findings suggest that LPS and MDP mediate anorexia through different cytokine mechanisms. A stronger up-regulation of anti-inflammatory cytokines (IL-1Ra and TGF-beta1) mRNA expression by MDP may be involved in the weaker MDP-induced anorexia relative to LPS. No significant changes were observed in the peptide components examined except for an up-regulation in cerebellar gp 130 mRNA and down-regulation of hypothalamic GR mRNA expression in response to LPS or MDP. This study shows that LPS and MDP induce anorexia in fasted rats allowed to refeed, and suggests an important role for endogenous cytokine-cytokine interactions.
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PMID:Lipopolysaccharide (LPS)- and muramyl dipeptide (MDP)-induced anorexia during refeeding following acute fasting: characterization of brain cytokine and neuropeptide systems mRNAs. 962 98

Immunologic complications of chronic renal failure are associated with the overproduction of proinflammatory cytokines by monocytes. This is partly due to renal failure itself but is further enhanced by hemodialysis treatment with frequent contact between blood and dialyzer membranes. Previous studies have shown an imbalance of proinflammatory and regulatory monokines in these patients. This study examines monokine production in hemodialysis patients using for the first time a very sensitive method of cytokine detection at a single-cell level by flow cytometry ("cytoflow technique"). Monocytes were stained intracellularly for the production of interleukin-6 (IL-6) and IL-10 after 20 h of culture with lipopolysaccharide. It was shown that high levels of proinflammatory IL-6 in hemodialysis patients are due to an increased number of monocytes producing this cytokine, while IL-6 synthesis per cell remains unchanged. In contrast, elevated levels of regulatory IL-10 are due to an increased synthesis per cell. This study demonstrates that in healthy subjects there is a population of monocytes producing exclusively IL-10 after 20 h of stimulation by lipopolysaccharide. This distinct population of regulatory monocytes is infrequent in dialysis patients, in whom most of the IL-10-positive monocytes also produce IL-6. These findings indicate that overproduction of proinflammatory factors in dialysis patients is at least in part due to a loss of cytokine-specific differentiation in monocytes.
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PMID:Production of proinflammatory and regulatory monokines in hemodialysis patients shown at a single-cell level. 972 78

End-stage renal disease is associated with a defect in immunologic functions. Previous studies have demonstrated that uremic ultrafiltrate (UUF) contains factors that suppress calcitriol synthesis and its biological actions. In the present study, the effect of UUF on basal and calcitriol-induced membrane bound CD14 expression of monocytes activated by phorbol 12-myristate 13-acetate was evaluated. CD14 acts as a receptor for the complexes of lipopolysaccharide and lipopolysaccharide-binding protein. Monocytes isolated from normal donors were used for the assay of monocyte CD14 expression. A calcitriol induced rise in monocyte CD14 expression (1966+/-423 to 2421+/-436 fluorescence intensity) was found. However, UUF not only suppressed basal CD14 expression of monocytes (from 1966+/-423 to 1240+/-203, P < 0.05) but also significantly blunted calcitriol-induced CD14 expression (from 2421+/-436 to 1744+/-229, P < 0.05). HPLC fractionated UUF collected from 8 to 16 min (fraction 1, F1) and from 25 to 40 min (fraction 3, F3) also significantly suppressed the expression of CD14. Because purine derivatives coeluted within F1, their effect on monocyte CD14 expression was also tested. Uric acid, xanthine, and hypoxanthine was found to suppress basal as well as calcitriol-induced CD14 expression of monocytes in a dose-dependent manner. In conclusion, UUF contains factors that impair calcitriol activated function of monocytes.
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PMID:Inhibition of calcitriol-induced monocyte CD14 expression by uremic toxins: role of purines. 977 83

Calcitriol modulates in vivoand in vitro cytokine production: A role for intracellular calcium. Background. Several immunomodulatory properties of calcitriol are currently known, however, only little information is available regarding the in vivo and in vitro effects of calcitriol on cytokine production in chronic renal failure. Methods. To study the in vitro effect of calcitriol on lipopolysaccharide (LPS)-induced cytokine production, peripheral blood mononuclear cells (PBMC, 2.5 ml/ml) from 12 chronic dialytic (HD), 15 undialyzed chronic renal failure (CRF) patients and 10 normal subjects (N) were incubated at 37 degrees for 12 hours with 100 ng of LPS (E. coli and P. maltofilia). Increasing doses of calcitriol from 10-10 to 10-9 M were added and cell associated TNF-alpha and IL-1beta were determined by immunoreactive tests after three freeze-thaw cycles. The intradialytic TNF-alpha and IL-1beta production were evaluated in vivo in 12 HD patients before and after three months of intravenous calcitriol treatment (6 microgram/week). Intracellular calcium [Ca++]i was determined on PBMC with a cytofluorimetric assay using FLUO-3 AM as the indicator. Results. In vitro, TNF-alpha increased from 3.6 +/- 1.9 pg/cell to 1797 +/- 337 in N, from 4.5 +/- 1.7 to 1724 +/- 232 in CRF and from 3.4 +/- 2.3 to 1244 +/- 553 in HD after the LPS stimulus. The production of TNF-alpha was inhibited by calcitriol in a dose-dependent manner [LPS + Vit.D3 100 ng, 2.9 +/- 2.1 in N, 3.7 +/- 1.9 in CRF and 3.4 +/- 1.7 in HD; LPS + Vit.D3 50 ng, 263 +/- 296 (N), 6.73 +/- 11 (CRF), 38 +/- 28 (HD); LPS + Vit.D3 25 ng = 873 +/- 583 (N), 325 +/- 483 (CRF), 588 +/- 507 (HD); LPS + Vit.D3 12.5 ng, 954 +/- 483 (N), 912 +/- 510 (CRF), 875 +/- 527 (HD)]. Comparable data were observed on IL-1beta production. In vivo, the intradialytic TNF-alpha increase (from 8.5 +/- 2.3 to 19 +/- 5.6 pg/2.5 x 106 cell) during hemodialysis was markedly reduced after calcitriol therapy (from 6.6 +/- 3.1 to 11 +/- 4.7). [Ca++]i decreased from 105 +/- 25 to 72 +/- 18 nM (P < 0.05) and a positive correlation between cytokine levels and [Ca++]i was found (r = 0.79; P < 0.001). Conclusions. The in vitro increase of cell-associated cytokine after LPS challenge was inhibited by calcitriol in a dose-dependent manner. These data suggest a possible in vivo modulatory effect of calcitriol therapy on cytokine production in hemodialysis.
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PMID:Calcitriol modulates in vivo and in vitro cytokine production: a role for intracellular calcium. 984 22

Nitric oxide (NO) is known to be involved in the modulation of neuroendocrine function. To clarify the role of different isoforms of NO synthase (NOS) in the neuroendocrine response to immune challenge, the expressions of neuronal NOS (nNOS) and inducible NOS (iNOS) genes in the hypothalamus following lipopolysaccharide (LPS) injection were examined using in situ hybridization. NOS activity was also determined by NADPH-diaphorase (NADPH-d) histochemistry. LPS (25 mg/kg) or sterile saline was injected intraperitoneally to male Wistar rats and the rats sacrificed 30 min, or 1, 2, 3, 5, 12 or 24 h after injection. nNOS mRNA expression in the paraventricular nucleus (PVN) was significantly increased 2 h after LPS injection. iNOS mRNA, which was not detected until 2 h after LPS injection, was significantly increased in the PVN 3 h after LPS injection. Both RNA expressions had returned to basal levels by 12 h after LPS injection. The number of NADPH-d positive cells was significantly increased 5 h after LPS injection. iNOS expression was more robust in parvocellular PVN, while nNOS was distributed mainly in the magnocellular PVN. Double in situ hybridization histochemistry revealed that some of the iNOS- (48.4%) or nNOS-positive cells (34. 3%) in the parvocellular PVN expressed CRF mRNA. The results demonstrate that LPS-induced sepsis causes significant increases in nNOS and iNOS gene expression with different time-courses and distributions, and that iNOS mRNA was more frequently co-localized with CRF-producing parvocellular neurons in the PVN. Thus, NO produced by iNOS and nNOS may play an important role in the neuroendocrine response to an immune challenge. Distinct differences in the distribution and time-course changes of iNOS and nNOS suggest different roles for the hypothalamic-pituitary-adrenal axis and/or neurohypophyseal system.
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PMID:Distinct distribution and time-course changes in neuronal nitric oxide synthase and inducible NOS in the paraventricular nucleus following lipopolysaccharide injection. 1006 18


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