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)

Here, we reported the effects of 17beta-estradiol (E2), isoflavone genistein (Gen), and daidzein (Dai) on the production of interferon (IFN)-gamma by splenocytes isolated from C57BL/6N mice. When mouse splenocytes were stimulated with lipopolysaccharide, E2, Gen, and Dai suppressed the production of IFN-gamma. However, when only nonadherent cell populations of splenocytes were tested, none of these estrogenic compounds suppressed IFN-gamma production. This result indicates that IFN-gamma production by nonadherent cell populations of splenocytes treated with estrogens is regulated by adherent cell populations. Moreover, direct cell-cell interaction between both populations was necessary for suppression of IFN-gamma production by nonadherent populations. In addition, E2 conjugated with bovine serum albumin inhibited IFN-gamma production as well as E2. This result suggests that the plasma membrane-associated estrogen receptor plays a prominent role in this suppression mechanism.
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PMID:Estrogenic compounds suppressed interferon-gamma production in mouse splenocytes through direct cell-cell interaction. 1460 42

To investigate the effects of the estrogen receptor-binding molecule bisphenol A (BPA) on murine immune function in vivo, we fed a low dose of 2.5 micro g BPA/kg body weight/day to both normal C57BL/6 and lupus-prone NZB X NZW F(1) (NZB/NZW) 5-week-old mice for 1 week. Analysis of concanavalin A (ConA)-stimulated splenic mononuclear cells by ELISA demonstrated that BPA-fed C57BL/6 males produced, on average, 40% less interferon-gamma (IFN-gamma; p < 0.01) and C57BL/6 females 28% less IFN-gamma (p < 0.05) compared with controls. Treated female NZB/NZW mice were monitored for lupus disease symptoms, defined as proteinuria (> 100 mg/dL albumin in urine for 2 consecutive weeks). Before the development of proteinuria, BPA-fed NZB/NZW mice produced significantly less ConA-stimulated IFN-gamma than did controls and displayed an average reduction of 50% in immunoglobulin G2a (IgG2a) antibody production from lipopolysaccharide (LPS)-stimulated splenocytes (p < 0.05). It is striking that 5-week-old female NZB/NZW mice fed a 7-day low-dose course of BPA developed proteinuria an average of 7 weeks later than did controls. Once proteinuria developed, splenocytes were stimulated with ConA for cytokine analysis. The BPA-fed mice showed a dramatic reduction of 64% in IFN-gamma production and a 32% reduction in ConA-stimulated interleukin-10 (p < 0.05). The long-lasting effects of BPA on IFN-gamma and IgG2a production likely contributed to the increased symptom-free period of the NZB/NZW mice.
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PMID:Effect of bisphenol A on murine immune function: modulation of interferon-gamma, IgG2a, and disease symptoms in NZB X NZW F1 mice. 1464 61

We have previously shown that 17beta-estradiol (E2) prevents the activation of brain macrophages, i.e. microglia cells, both in vitro and in vivo. Hormone exerts this inhibitory effect by inhibiting pro-inflammatory gene expression. In this study we further investigated on the molecular mechanism of E2 action in the RAW 264.7 macrophage cell line. We show here that these cells express the alpha-isoform of the estrogen receptor (ERalpha) and not ERbeta. Similarly to its activity in brain macrophages, E2 is able to inhibit the activation program induced by lipopolysaccharide (LPS) in RAW 264.7 cells, as shown by the inhibitory effect of hormone on the morphological conversion and matrix metalloproteinase-9 (MMP-9) expression induced by the endotoxin. In addition, we demonstrate that hormone treatment is not associated with a reduction in the steady-state expression of Toll-like receptor-4 (TLR-4) and CD14, two components of the LPS receptor complex. Our results further confirm the anti-inflammatory role of ERalpha in macrophages and propose that the mechanism of hormone action on macrophage reactivity involves signaling molecules which are down-stream effectors of the LPS membrane receptors.
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PMID:Regulation of the lipopolysaccharide signal transduction pathway by 17beta-estradiol in macrophage cells. 1526 8

The major objective of this experiment was to determine whether the bovine placenta could be stimulated to secrete progesterone, since the bovine placenta secretes little progesterone when the corpus luteum is functional. Secondly, we wanted to determine whether reported abortifacients or progesterone or estrogen receptor antagonists affected bovine placental prostaglandin secretion. The ovine placenta secretes half of the circulating progesterone at day 90 of pregnancy and PGE2 appears to regulate ovine placental progesterone secretion. Calcium has been reported to regulate placental progesterone secretion in cattle. Diced 186-245-day placental slice explants from six Brahman and six Angus cows were incubated in vitro at 39.5 degrees C under 95% air: 5% CO2 at pH 7.2 in 5 ml of M-199 for 1 h in the absence of treatments and for 4 and 8 h in the presence of treatments. Treatments were: vehicle; R24571; compound 48/80; IP3; PGE2; CaCl2; cyclosporin A; lipopolysaccharide (endotoxin) from Salmonella abortus equi., enteriditis, and typhimurium; monensin; ionomycin; arachidonic acid; mimosine; palmitic acid; progesterone, androstenedione; estradiol-17beta; A23187; RU-486; or MER-25. Jugular and uterine venous plasma and culture media were analyzed for progesterone, PGE2 and PGF2alpha by radioimmunoassay (RIA). Plasma hormone data were analyzed by a One-Way Analysis of Variance (ANOVA). Hormone data in culture media were analyzed for breed and treatment effects by a Factorial Design (2 breeds, 2-range of days, 21 treatments) for ANOVA (2 x 2 x 21). Since hormone data secreted by placental tissue in vitro did not differ (P > or = 0.05) by breed or range of days of pregnancy, data were pooled and analyzed by a One-Way ANOVA. Concentrations of PGE2 in uterine venous blood were two-fold greater (P < or = 0.05) in Angus than Brahman cows. PGE2 and PGF2alpha in vehicle controls increased from 4 to 8h (P < or = 0.05), but not progesterone (P > or = 0.05) Progesterone in culture media treated with RU-486 increased (P < or = 0.05) at 4 and 8 h compared to vehicle controls and was not affected by other treatments (P > or = 0.05). Concentrations of PGE2 in media at 4 and 8 h were lower (P < or = 0.05) when compared to controls except treatment with PGE2 at 4 and 8h and RU-486 at 8h (P > or = 0.05). PGF2alpha was increased (P < or = 0.05) by RU-486 at 8h and no other treatment affected PGF2alpha at 4 or 8 h (P < or = 0.05). In conclusion, modulators of cellular calcium signalling pathways given alone do not affect bovine placental progesterone secretion at the days studied and progesterone receptor-mediated events appear to suppress placental progesterone, PGF2alpha, and PGE2 secretion in cattle. In addition, PGE2 does not appear to regulate bovine placental progesterone secretion when the corpus luteum is functional and bacterial endotoxin does not appear to affect bovine placental secretion of PGF2alpha or PGE2.
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PMID:Do calcium-mediated cellular signalling pathways, prostaglandin E2 (PGE2), estrogen or progesterone receptor antagonists, or bacterial endotoxins affect bovine placental function in vitro? 1528 56

Previous studies reported the ability of raloxifene to acutely relax arterial and venous vessels, but the underlying mechanisms are controversial. Anti-inflammatory effects of the drug have been reported in nonvascular tissues. Therefore, the aim of this study was to investigate the nature of short- and long-term effects of raloxifene on selected aspects of vascular function in rat aorta. Isometric tension changes in response to raloxifene were recorded in aortic rings from ovariectomized female rats that underwent estrogen replacement, whereas long-term experiments were performed in isolated aortic smooth muscle cells (SMCs). Raloxifene (0.1 pM-0.1 microM) induced acute vasorelaxation through endothelium- and nitric oxide (NO)-dependent, prostanoid-independent mechanisms. The relaxant response to raloxifene was significantly weaker than that to 17beta-estradiol and was sensitive to neither the nonselective estrogen receptor antagonist ICI 182,780 [7,17-[9[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol] nor a selective estrogen receptor (ER) alpha antagonist. This rapid vasorelaxant effect was retained in aortic rings from rats treated with 0.1 mg/kg, but not 1 mg/kg, lipopolysaccharide, 4 h before sacrifice. In cultured aortic SMCs, raloxifene treatment (1 nM-1 microM) for 24 h reduced inducible NO synthase activation in response to cytokines. This effect was prevented by the selective ERalpha antagonist and was associated with up-regulation of ERalpha protein levels, which dropped markedly upon cytokine stimulation. These findings illustrate the relevance of classic ER-dependent pathways to the vascular anti-inflammatory effects rather than to the nongenomic vasorelaxation induced by raloxifene and may assist in the design of novel ER isoform-selective estrogen-receptor modulators targeted to the vascular system.
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PMID:Raloxifene elicits combined rapid vasorelaxation and long-term anti-inflammatory actions in rat aorta. 1694 57

The effects of estrogen therapy can differ depending on the regimen of estrogen administration. In addition, estrogen can modulate the effects of stressors. To examine the interaction between these systems, we infused adult female rats with lipopolysaccharide (LPS) into the fourth ventricle of the brain for 6 d and compared the effects of constant and pulsed estrogen replacement. Constant, but not pulsed, estrogen treatment reduced estrogen receptor-alpha (ERalpha) protein by 90% in the uterus and increased heat-shock proteins 70 and 90 by 74 and 48%, respectively, whereas progesterone receptor levels increased in all ovariectomized rats receiving estrogen replacement. In contrast to the uterine decline in ERalpha, no changes in ERalpha were observed in the hypothalamus or hippocampus, and ERbeta levels were unchanged in all regions tested. Brain infusion of LPS did not alter these proteins but increased the number of activated microglia in the thalamus and reduced body weight in all rats as well as activated the hypothalamic-pituitary-adrenal axis in ovariectomized rats, as determined by elevations in circulating corticosterone and progesterone. Estrogen treatments did not alter these markers, and no differences were observed in cortical choline acetyltransferase activity or nitrotyrosine for any of the treatment groups. The current study found an unexpected increase in uterine weight in lipopolysaccharide-infused rats treated with constant, but not pulsed, estrogen. This report suggests that constant and pulsed regimens of estrogen administration produce different effects and that stress may be an important factor in the postmenopausal intervention with estrogen.
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PMID:Brain infusion of lipopolysaccharide increases uterine growth as a function of estrogen replacement regimen: suppression of uterine estrogen receptor-alpha by constant, but not pulsed, estrogen replacement. 1702 24

Activation of the estrogen receptor-alpha (ERalpha) mediates the vasculoprotective effects of estrogen, in part, through modulating nitric oxide (NO) production and vasodilation. Whereas inflammation is accompanied by altered vascular reactivity and underlies the pathogenesis of vascular disease, the role of the ERalpha in the vascular responses associated with acute systemic inflammation remains poorly characterized. Contractile and relaxation responses of isolated aortic segments were investigated 12 h after ip injection of saline or lipopolysaccharide (LPS, 10 mg/kg) in male wild-type (ERalpha(+/+)) and ERalpha-deficient (ERalpha(-/-)) mice. As previously observed, LPS-injected ERalpha(+/+) mice displayed reduced contractile responses to phenylephrine and enhanced vasodilation in response to acetylcholine. In contrast, aortic tissues from LPS-injected ERalpha(-/-) mice displayed enhanced contractile responses and reduced sensitivity to acetylcholine- and sodium nitroprusside-induced vasodilation. LPS treatment in ERalpha(+/+) and ERalpha(-/-) mice resulted in similar increased levels of systemic NO production and inducible NO synthase expression in the vascular wall. However, expression of mRNA and protein for endothelial NOS and soluble guanylate cyclase (alpha- and beta-subunits) were significantly reduced in aortic tissues from LPS-treated ERalpha(-/-) animals, possibly accounting for reduced endothelial NO production and reduced smooth muscle responses to NO. These findings represent new evidence of the functional role of ERalpha in the male vasculature and suggest that during acute LPS-induced inflammatory responses, the ERalpha mediates the sustained expression of the molecular machinery essential for endothelial NO synthesis (i.e. endothelial NOS) and the vascular responses to NO (i.e. soluble guanylate cyclase).
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PMID:Compromised aortic vasoreactivity in male estrogen receptor-alpha-deficient mice during acute lipopolysaccharide-induced inflammation. 1715 9

Previously, we reported that cartilage is an estrogen receptor (ER) positive tissue and that mRNA levels of ERbeta increase in postmenopausal women with osteoarthritis. Based on our findings and those of other investigators, we hypothesized that local rather than circulating estrogen levels negatively affect chondrocyte metabolism and that selective ER modulators (SERM) augment cartilage health. To test the latter part of our hypothesis, we explored the role of genistein, a naturally occurring SERM with high affinity to bind ERbeta, in inhibiting the lipopolysaccharide (LPS)-stimulated cyclooxygenase (COX)-2 in chondrocytes. Primary cultures of normal human chondrocytes were treated with three levels of genistein (0, 50, and 100 microM). After 1 h, the genistein-treated cells were stimulated by 1 microg/ml LPS for 24 h. Cells were then harvested, and the cytosolic fraction was isolated for assessment of COX-1 and COX-2 protein levels using Western analysis. Nitric oxide (NO), interleukin-I beta (IL-1beta), and human cartilage glycoprotein 39 (YKL-40) production was also measured in cell supernatants. NO and IL-1beta were measured as markers of inflammation, and YKL-40 was assessed as a marker of cartilage catabolism. Genistein had no significant effect on either YKL-40 or IL-1beta levels. Our data indicate that the LPS-stimulated increases in COX-2 protein level and NO in supernatant are reduced by pretreatment of genistein, whereas COX-1 protein level is not affected by genistein. The ability of genistein to suppress COX-2 but not COX-1 is advantageous because suppressing COX-2 can lead to suppression of proinflammatory molecules. Although genistein suppresses COX-2 production, it does not affect the production of COX-1 enzyme, which is responsible for releasing prostaglandins involved in cellular house-keeping functions such as the maintenance of gastrointestinal integrity and vascular homeostasis.
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PMID:Genistein reduces the production of proinflammatory molecules in human chondrocytes. 1736 82

To examine the influence of acute resistive exercise and "hormone status" on cytokine profile, 35 postmenopausal women (72 +/- 6.2 yr) underwent a moderate-high-intensity resistive exercise bout or rested. There were 4 groups: no hormone replacement (NHR, n = 9), hormone replacement (HRT, n = 12), selective estrogen receptor modulator (SER, n = 7), or resting control (no hormone replacement, CON, n = 7). NHR, HRT, and SER exercised (3 sets, 10 exercises @ 80 % 1RM). Blood was collected pre-exercise (PR), postexercise (PO), and two hours (2H) postexercise (same times for CON). Blood was diluted 1 : 10 in culture medium and incubated (37 degrees C, 5 % CO2, 24 h) with lipopolysaccharide (LPS, 25 microg . ml (-1)). Serum and supernatant from LPS-stimulated blood were analyzed for IL-6, IL-1 beta, and TNF-alpha using ELISA. Resistive exercise increased PO serum IL-6, and PO LPS-stimulated IL-6 and IL-1 beta in the exercise groups (HRT, NHR, SER collapsed; EX, n = 28). LPS-stimulated IL-1 beta remained elevated at 2H in EX and was significantly higher than PR in CON at 2H. Expressed per monocyte, EX had significantly lower IL-1 beta and TNF-alpha LPS-stimulated production at PO and 2H compared to CON, indicating an exercise-induced blunting of an apparent diurnal response on cytokine production. In postmenopausal women, acute resistive exercise increased circulating IL-6, but reversed an apparent diurnal increase in LPS-stimulated IL-1 beta and TNF-alpha production with no influence of hormone replacement or raloxifene.
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PMID:Resistive exercise blunts LPS-stimulated TNF-alpha and Il-1 beta. 1799 Feb 10

Since the endocrine and immune systems share portions of some intracellular signaling pathways, endocrine-disrupting chemicals (EDCs) are considered potential agents for influencing inflammatory responses. Here, we investigated the effect of EDCs on lipopolysaccharide (LPS)-induced NO production and NF-kappaB activation in the RAW264.7 mouse macrophage cell line. Five phenol-containing EDCs were investigated, namely bisphenol A (BPA), the alkyl phenols p-n-nonylphenol (NP) and p-n-octylphenol (OP), and the chlorinated phenols 2,4-dichlorophenol (DCP) and pentachlorophenol (PCP). Our results revealed that these chemicals dose-dependently suppressed LPS-induced NO production, as reflected by decreased NO(x) content. The suppressive effects of BPA, NP and OP, but not PCP or DCP, were blocked by the estrogen receptor (ER) inhibitor, ICI182780. ELISA-based quantification of the DNA-binding activity of free p65 NF-kappaB showed that LPS-induced NF-kappaB activation was significantly diminished by EDC treatment. Furthermore, immunocytochemical analysis of 8-nitroguanosine, a unique index of NO-mediated signaling, showed that 8-nitroguanosine formation increased in LPS-stimulated cells, but this increase was inhibited by the tested EDCs. These results demonstrate that EDCs suppress NO production and NF-kappaB activation in LPS-stimulated macrophages through ER-dependent (BPA, NP, OP) and -independent (PCP, DCP) pathways. The EDCs further inhibited 8-nitroguanosine formation, suggesting that they interfere with NO-mediated signaling. Thus, EDCs might play important roles in the inflammatory response and host defense system against foreign pathogens.
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PMID:Suppression of NO production and 8-nitroguanosine formation by phenol-containing endocrine-disrupting chemicals in LPS-stimulated macrophages: involvement of estrogen receptor-dependent or -independent pathways. 1825 6


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