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)

The antibody response to SRBC and E. coli 0127 lipopolysaccharide were determined in offspring from mice exposed in utero to diethylstilbestrol. The antibody response to SRBC, a T-cell dependent antigen, was similar in control and exposed animals. In contrast, the LPS antibody response was suppressed in treated females and enhanced in treated males. These studies indicated that in utero exposure to DES alters the humoral immune system to T-independent antigens.
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PMID:Alterations of the antibody response following in utero exposure to diethylstilbestrol. 36 5

Media conditioned by an interleukin 3 (IL-3)-producing T-cell line, STIL-3, as well as recombinant mouse IL-3 showed granulocyte/macrophage (GM) colony-stimulating activity in the semi-solid culture medium containing horse serum (HS) or bovine serum, but the activity was not apparent when fetal calf serum (FCS) was used. No such serum-dependency of GM colony formation was observed when abdominal wall conditioned medium or L-cell conditioned medium containing GM colony-stimulating factor was used. Although the levels of albumin and total protein were lower in FCS than HS, increase of FCS concentration did not affect the GM colony-stimulating activity of IL-3. Addition of bovine serum albumin (BSA) preparation to FCS, however, increased the number of GM colonies to the same level as that observed with HS. The levels of bacterial lipopolysaccharide (LPS) in sera and BSA and the effect on the bone marrow cells from LPS-nonresponsive C3H/HeJ mice indicated that the observed effect of BSA was not due to the contaminating LPS. The activity of BSA was not substituted by IL-1, IL-2, IL-4, IFN-gamma, TNF, NGF or erythropoietin. The present study suggests the presence in BSA of co-factor(s) of IL-3 in stimulating GM colony formation.
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PMID:Presence of an activity indispensable for the granulocyte/macrophage colony-stimulating activity of interleukin 3 in bovine serum albumin. 217 34

Adult female (C57BL/6 X C3H)F1 (B6C3F1) mice were treated with diethylstilbestrol for 14 days and assayed for the ability to produce antibody to a T-dependent antigen, a T-independent antigen, and to respond in vitro to stimulation by a polyclonal activator, bacterial lipopolysaccharide (LPS). No suppression of the in vivo antibody responses were observed. DES produced a subtle alteration in the response to the T-dependent antigen, sheep erythrocyte (sRBC), as treated groups maintained higher PFC values than vehicle groups after the peak day of the response. DES induced an enhanced response to the T-independent antigen, DNP-Ficoll. Spleen cells from DES-exposed animals were only marginally altered in their ability to produce antibody in vitro in response to LPS. Parallel experiments indicated a comparable reduction of LPS-induced blastogenesis. Serum immunoglobulin levels were determined following DES exposure, as a measure of baseline immunocompetence. DES only caused a reduction in the immunoglobulin M (IgM) isotype. DES exposure caused a significant enhancement of the activity of the reticuloendothelial (RES) system. Experiments were performed to assess the effects of enhanced RES function on concentrations of 51Cr labeled sRBC, which were optimal for antibody production. When sRBC were administered i.p., there was no effect on either the Ab response (as reported above) or on the number of sRBC localized in the spleen. In contrast, when sRBC were administered i.v., exposure to DES reduced (approximately 50%) both the Ab response and the number of sRBC localized in the spleen. Enhanced phagocytic function and alterations in antigen distribution must be considered in the interpretation of in vivo immune responses.
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PMID:Effects of subchronic exposure to diethylstilbestrol on humoral immune function in adult female (C3B6)F1 mice. 653 73

The human platelet-activating factor receptor gene exists as a single copy on chromosome 1. Two 5'-noncoding exons (Exon 1 and 2) has distinct transcription initiation sites and promoters. These exons are alternatively spliced to a common splice acceptor site on exon 3 that contains a total coding regions. The transcript 1 is expressed ubiquitously with an emphasis of differentiated eosinophilic cell line (Eol-1), and leukocytes. On the other hand, the transcript 2 is expressed tissue-specifically. The latter is not expressed in leukocytes or brain. The transcript 1 has three tandem repeats of NF-kappa B, and SP-1 site, and responded to various inflammatory reagents including PAF itself, lipopolysaccharide, or phorbol ester. By northern blotting of tissue or cells with various nutritional or hormonal treatments, the PAF receptor messages are up-regulated. Estrogen increased the expression of the PAF receptor in human endometrial glandular cells, and vitamin A (retinoic acid) or thyroid hormone treatment up-regulates the PAF receptor expression only tissues with transcript 2 By various in vivo and in vitro transcriptional assays (CAT reporter assay, gel mobility shift assay), we identified estrogen responsible element, and hormone responsive element. The PAF receptor hormone responsive element is composed of three direct repeated TGACCT-like hexamer motifs with 2 and 4 bp spaces, and the two upstream and two downstream motifs were identified as response elements for RA and T.
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PMID:Platelet-activating factor receptor. Gene structure and tissue-specific regulation. 913 Nov 30

While estrogen is known to prevent the development of atherosclerosis, the mechanism is not completely understood. We investigated the effects of superoxide dismutase, acetylcholine, and other compounds on the release of nitric oxide (NO) by measuring the relaxation responses of aortic rings, with and without intact endothelium, taken from rabbits under various experimental conditions. The aorta of female rabbits released a greater amount of NO than did that of oophorectomized females and male rabbits. The greater basal release of NO in female rabbits was decreased in animals with atherosclerosis induced by a high cholesterol diet. We also investigated the effect of estrogen on endothelial, neuronal and inducible NO synthase (NOS), NOS-3, NOS-1 and NOS-2, respectively. Preincubation with a physiologic concentration of 17 beta-estradiol (10(-12) to 10(-8) M) over 8 h significantly enhanced the activity of NOS-3 in the endothelial cells of cultured human umbilical vein and bovine aortas. 17 beta-Estradiol also enhanced the release of NO from endothelial cells as measured by an NO selective meter and NO2-/N/3-, metabolites of NO. Western blot showed a similar effect of 17 beta-estradiol on NO. Estrogen increased NOS-3 via a receptor-mediated system. Low concentrations of 17 beta-estradiol (10(-10) to 10(-8) M) enhanced the activity of crude NOS-1 in the cytosolic fraction of rabbit cerebella. Partially purified NOS-1, obtained from the cytosolic fraction by DEAE column chromatography, had a similar response to estrogen. Estrogen at a low dose enhanced the fluorescence of dansyl calmodulin and augmented it in high doses. We also investigated the effect of estrogen on NOS-2. When J774 cells, a murine macrophage cell line, were incubated with interferon-r and lipopolysaccharide, NOS-2 was induced and a large amount of NO was released. Pre- or co-incubation of 17 beta-estradiol inhibited the induction of NOS-2 protein and NO release. The estrogen receptor antagonists, tamoxifen and ICI 182780, inhibited that effect of 17 beta-estradiol. 17 beta-Estradiol inhibited the induction of NOS-2 by a receptor-mediated system. These results may offer a new mechanism for the anti-atherosclerotic effect of 17 beta-estradiol.
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PMID:Effect of estrogen on isoforms of nitric oxide synthase: possible mechanism of anti-atherosclerotic effect of estrogen. 918 36

The present study was undertaken to determine whether sex hormones influence nitric oxide synthase levels in the kidney. Five groups of rats were studied: males, castrated males, females, oophorectomized females, and oophorectomized females receiving estradiol replacement therapy. Endothelial nitric oxide synthase (eNOS) levels in the kidney were measured by Western blotting. eNOS levels were significantly greater in the renal medulla of female rats compared with male rats (3545 +/- 473 versus 2418 +/- 205 densitometry units (DU), P < 0.05). Oophorectomy reduced renal medullary eNOS levels to that of intact male rats (2566 +/- 304 DU, P = NS). Estrogen replacement therapy significantly increased medullary eNOS levels in oophorectomized animals (3249 +/- 377 versus 2302 +/- 213 DU, P < 0.05). Renal inducible nitric oxide synthase (iNOS) levels were measured after induction with lipopolysaccharide. iNOS levels were significantly greater in the renal medulla of female rats compared with male rats (677 +/- 253 versus 252 +/- 12 DU, P < 0.05). Oophorectomy reduced renal medullary iNOS levels to that of intact male rats (295 +/- 57 DU, P = NS). In contrast, estrogen replacement therapy significantly increased medullary iNOS levels in oophorectomized animals (682 +/- 356 versus 160 +/- 92 DU, P < 0.05). Steady-state levels of mRNA for iNOS were found to be higher in the inner medulla of female rats compared with male rats (1519 +/- 211 versus 899 +/- 105 DU, P < 0.05). In contrast to these findings, sex hormones failed to influence nitric oxide production or iNOS levels in lipopolysaccharide-stimulated mesangial cells in culture. These results suggest that gender may influence renal medullary synthesis of nitric oxide.
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PMID:Sex hormones and renal nitric oxide synthases. 925 50

Estrogen pretreatment has been reported to protect rats from death induced by endotoxin. We investigated the effects of posttreatment with a synthetic estrogen, ethynylestradiol, on arterial pressure and hemodynamics in thiobutabarbitone-anesthetized rats challenged with Escherichia coli lipopolysaccharide. Rats were i.v. injected with lipopolysaccharide (1 mg/kg) followed by vehicle or a single dose of ethynylestradiol (0.25, 0.5, or 1 mg/kg) 1 h later. Another group (time-matched control) was given the vehicle. In the time-control group, there was a slight decrease in mean arterial pressure (-10 +/- 3 mm Hg) but no significant changes in cardiac output, total peripheral resistance, or heart rate over the 6-h study period. Lipopolysaccharide progressively reduced mean arterial pressure and cardiac output (-27 +/- 8 mm Hg and -52 +/- 6 ml/min, after 6 h) and increased total peripheral resistance and heart rate (+0.33 +/- 0.10 mm Hg/min/ml and +21 +/- 13 beats/min, after 6 h). None of the time-control rats died, but 36% of the rats treated with lipopolysaccharide died between 3 and 6 h after endotoxin challenge. Ethynylestradiol, at 0.25 and 0.5 completely, and at 1 mg/kg partially, restored mean arterial pressure and cardiac output at 6 h after injection of lipopolysaccharide. Ethynylestradiol at 0.5 and 1 mg/kg, but not 0.25 mg/kg, completely reversed the increase in total peripheral resistance at 6 h after injection of lipopolysaccharide. Mortality was 14% in each of the three groups of rats given ethynylestradiol 1 h after lipopolysaccharide. Therefore posttreatment with ethynylestradiol attenuated hemodynamic changes in endotoxic shock.
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PMID:Protective effects of ethynylestradiol on the hemodynamic changes induced by lipopolysaccharide in anesthetized rats. 955 92

Estrogen replacement therapy (ERT) is known to prevent bone loss following the menopause, but the mechanism for this is unclear. Estrogen may suppress the secretion of certain bone-resorbing cytokines. The aim of this study was to assess the effect of ERT on the levels of cytokines measured in peripheral blood. We measured cytokines in 10 postmenopausal women (ages 56-59, 3-9 years since menopause) treated with ERT and 10 age-matched (54-59 years, 4-10 years since menopause) untreated women as controls. Samples of blood were taken and used for mononuclear cell cultures, whole blood (WB) cultures, and the separation of serum. The cultures were treated with lipopolysaccharide (LPS; 500 ng/ml) and hydrocortisone (10(-6) M). The conditioned medium from cultures and the serum were then assayed for interleukin-6 (IL-6), IL-1alpha IL-1beta, IL-1 IL-1ra, tumor necrosis factor alpha (TNF-alpha), and granulocyte macrophage colony stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. M-CSF and the soluble cytokine receptors soluble IL-6 receptor (sIL-6r) and soluble TNF receptor type 1 (sTNFr1) were also measured in serum and M-CSF in stimulated WB cultures. Measurements were corrected for mononuclear cell count. We also measured serum bone-specific alkaline phosphatase (ibAP) in all subjects. We found that LPS stimulated secretion of all cytokines both in WB and isolated cell cultures, and that this was attenuated by hydrocortisone. A significantly higher ratio of IL-1beta/IL-1ra (p = 0.02) in LPS stimulated WB cultures was seen in the untreated women. Levels of IL-1beta and IL-1alpha measured in WB cultures were lower and IL-1ra was higher in the ERT-treated group but these results were not significant. BAP was higher in the untreated group (p = 0.005) and correlated with IL-alpha/IL-1ra in the whole group (r = 0.49, p = 0.03). Results of other measurements showed no significant differences between groups. We conclude that estrogen may prevent bone loss following the menopause by altering the balance between IL-1beta and IL-1ra.
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PMID:Effects of estrogen therapy of postmenopausal women on cytokines measured in peripheral blood. 978 46

The ability of estrogen to prevent glucocorticoid-induced apoptosis in osteoblasts was studied both in vitro and in vivo. Glucocorticoid treatment for 72 h produced a dose-dependent increase in the number of apoptotic cells, determined by acridine orange/ethidium bromide staining, with a maximal response of 31+/-2% and 26+/-3% with 100 nM corticosterone in primary rat and mouse osteoblasts, respectively. Simultaneous administration of varying concentrations of 17beta-estradiol and 100 nM corticosterone decreased apoptotic osteoblasts in a dose-dependent manner, with a maximal decrease of 70% with 0.01 nM 17beta-estradiol. Terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling also demonstrated glucocorticoid-induced DNA fragmentation that was inhibited by estrogen. Estrogen was shown to inhibit apoptosis induced by lipopolysaccharide treatment. As early as 6 h, Western blots demonstrated a dose-dependent decrease in the Bcl-2/Bax ratio, which reached a minimum of 0.18 in osteoblasts treated with 1000 nM corticosterone for 72 h. This reduction in Bcl-2/Bax was abolished by treating osteoblasts simultaneously with 17beta-estradiol, but not with 17alpha-estradiol. In 7-day-old mice, administration of varying concentrations of dexamethasone for 72 h resulted in a dose-dependent increase in the number of apoptotic osteoblasts as demonstrated by in situ terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling staining of calvaria. A maximum of 22+/-1% apoptotic osteoblasts on the bone surface was found with 1 mg/kg BW dexamethasone compared with 2+/-1% in vehicle-treated mice. Injection of varying concentrations of 17beta-estradiol (0.5-5 mg/kg BW), but not 17alpha-estradiol, with 1 mg/kg dexamethasone produced a dose-dependent decrease in the number of apoptotic osteoblasts to 5+/-1% with 5 mg/kg 17beta-estradiol. Thus, glucocorticoid-induced apoptosis of osteoblasts may be prevented at least in part by 17beta-estradiol.
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PMID:Estrogen prevents glucocorticoid-induced apoptosis in osteoblasts in vivo and in vitro. 1053 65

In the present study the effects of 17beta-estradiol on microglial activation are described. Estrogen replacement therapy has been associated with decreased severity of age-related neurodegenerative diseases such as Alzheimer's disease, and estrogens have potent immunosuppressive properties outside of the brain. To determine the role that microglial cells might play in estrogen-mediated neuroprotection, primary rat microglia and N9 microglial cell lines were treated with increasing doses of 17beta-estradiol before or during immunostimulation by lipopolysaccharide, phorbol ester, or interferon-gamma. Pretreatment with 17beta-estradiol, but not 17alpha-estradiol or progesterone, dose dependently attenuated microglial superoxide release and phagocytic activity. Additionally, 17beta-estradiol attenuated increases in inducible nitric oxide synthase protein expression, but did not alter nuclear factor-KB activation. The antiinflammatory effects of 17beta-estradiol were blocked by the antiestrogen ICI 182,780. Additionally, 17beta-estradiol induced rapid phosphorylation of the p42/p44 mitogen-activated protein kinase (MAP kinase), and the MAP kinase inhibitor PD 98059 blocked the antiinflammatory effects of 17beta-estradiol. Overall, these results suggest that estrogen receptor-dependent activation of MAP kinase is involved in estrogen-mediated antiinflammatory pathways in microglial cells. These results describe a novel mechanism by which estrogen may attenuate the progression of neurodegenerative disease and suggest new pathways for therapeutic intervention in clinical settings.
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PMID:Antiinflammatory effects of estrogen on microglial activation. 1101 19


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